Composition for predicting drug responsiveness and use thereof

WO2026206007A1PCT designated stage Publication Date: 2026-10-01UI (UNIVERSITY IND FOUNDATION) YONSEI UNIVERSITY
View PDF 0 Cites 0 Cited by

Patent Information

Application Number
PCT/KR2026/004805
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2025-03-27
Filing Date
2026-03-26
Publication Date
2026-10-01

Smart Images

  • Figure KR2026004805_01102026_PF_FP_ABST
    Figure KR2026004805_01102026_PF_FP_ABST
Patent Text Reader

Abstract

The present invention relates to a composition for predicting responsiveness to a PARP inhibitor drug mainly used for the treatment of prostate cancer. By predicting the suitability of using the therapeutic agent for a prostate cancer patient before administration and providing accurate basic information so that an appropriate alternative anticancer agent can be used in a future treatment plan by a clinician, the composition is expected to reduce the cost burden on patients and also increase survival rates.
Need to check novelty before this filing date? Find Prior Art

Description

Composition for predicting drug responsiveness and use thereof

[0001] The present invention relates to a composition for predicting the responsiveness of an anticancer drug and a method for predicting the responsiveness of an anticancer drug using the same.

[0002]

[0003] Pharmacogenomics is the study of genetic characteristics that influence a subject's response to drug treatment. By analyzing genetic information involved in the action and metabolism of drugs, it can aid in providing personalized treatment for patients. In a clinical setting, pharmacogenomics can enable physicians to select appropriate drugs and dosages for each individual patient. This is particularly important in diseases such as cancer, which exhibit extensive heterogeneity regarding treatment responsiveness and prognosis prediction.

[0004] Prostate cancer is the most common cancer among men worldwide and ranks second in mortality. It typically affects men over the age of 50, and the number of patients increases rapidly with age. While it usually progresses slowly, it becomes an extremely difficult disease to treat once it develops into a malignant form and metastasizes. Metastasis primarily begins in the lymph nodes surrounding the prostate, as well as in the pelvic bones, vertebrae, and bladder, gradually spreading throughout the body.

[0005] In particular, prostate cancer is a type of cancer where genetic and molecular profiles can vary significantly from patient to patient. Some types of prostate cancer involve mutations in HRR-related genes such as BRCA1, BRCA2, and ATM, and these mutations determine sensitivity to specific targeted therapies. Additionally, androgen receptor (AR) mutations or overexpression, as well as the activation of other signaling pathways, can also differ among patients. Since these factors significantly influence the response to or resistance to hormone therapy, there is a practical need for a metric to gauge treatment efficacy in advance, enabling the selective use of personalized medications tailored to each individual to improve survival rates after treatment.

[0006] Accordingly, the inventors of the present invention arrived at the present invention by conducting diligent research with the goal of maximizing the therapeutic effect while minimizing side effects, and by discovering a combination of markers capable of predicting the response to a specific drug through patient gene profiling.

[0007]

[0008] One objective of the present invention is to provide a composition capable of predicting responsiveness to a drug.

[0009] Another objective of the present invention is to provide a kit capable of predicting responsiveness to a drug.

[0010] Another objective of the present invention is to provide a method for predicting responsiveness to a drug.

[0011] However, the technical problems that the present invention aims to solve are not limited to those mentioned above, and other unmentioned problems will be clearly understood by those skilled in the art from the description below.

[0012]

[0013] Various embodiments described herein are described with reference to the drawings. In the following description, for a complete understanding of the invention, various specific details, such as specific forms, compositions, and processes, are described. However, specific embodiments may be practiced without one or more of these specific details, or in combination with other known methods and forms. In other examples, known processes and manufacturing techniques are not described as specific details so as not to unnecessarily obscure the invention. Reference throughout this specification to "one embodiment" or "an embodiment" means that the particular features, forms, compositions, or characteristics described in association with the embodiment are included in one or more embodiments of the invention. Accordingly, the context of "in one embodiment" or "an embodiment" expressed at various places throughout this specification does not necessarily represent the same embodiment of the invention. Additionally, particular features, forms, compositions, or characteristics may be combined in any suitable way in one or more embodiments.

[0014] Unless otherwise specifically defined in the specification, all scientific and technical terms used herein have the same meaning as commonly understood by those skilled in the art to which the present invention pertains.

[0015]

[0016] According to one embodiment of the present invention, the invention relates to a composition for predicting drug responsiveness.

[0017] In the present invention, the composition is LIM2, GTF2IP6, LINC02022, LILRP2, MYMX, LINC02730, RN7SL391P, RNA5SP468, LINC02209, PWWP4, DDR1.DT, KRT8P38, GAPDHP55, TRPC7.AS2, LINC01923, TSIX, KRTAP4.3, ANKRD34C.AS1, SNORD115.27, RPL18AP16, CYP2AB1P, SP7, GRM8.AS1, KASH5, CCDC63, TRPM5, SERPINA12, SCGB1D4, TBC1D3P6, ANKRD30A, LINC00993, PDLIM5, EEF1A1P5, RPL7, NKX3.1, HSP90B1, EEF1A1, It may include a preparation for measuring the expression level of at least one gene selected from the group consisting of RPS24, RPL4, TMPRSS2, HSP90AA1, TPD52, TPT1, HNRNPA1, HNRNPH1, EEF1A1P6, P4HB, NDRG1, FASN, and B2M, or a protein encoded by it.

[0018] In the present invention, the composition comprises ATP4A, PTH2, C1QL4, DSCR8, LINC02954, EIF4A1P9, CASC23, HES3, HTR3D, ATP2B3, SVOP, OR5AU1, CACNG2, PSG3, LINC02403, RN7SKP186, LHX1.DT, PDLIM1P1, GALP, KRT33A, OSBPL9P5, OR5AN1, GFY, RPL17P2, MIR5089, TMEM239, OTOAP1, CALML5, OR4K1, HSPD1P4, RN7SL219P, RPL17P11, SPRYD7P1, RNU6.949P, OR2Q1P, OR4K15, KRT8P51, ANKRD26P2, ANAPC10P1, LINC01517, MIR194.2HG, OR5B15P, RN7SKP205, LACRT, DNM1P5, KRTAP3.3, LINC01651, KRT26, KRT223P, INGX, B3GNT2P1, TUBA3GP, C10orf90, RPL15P20, XRCC6P3, LHX3, PCK1, LINC00661, C1QTNF1.AS1, ZAN, PSG1, NCOA4P4, BARHL1, RTP3, GSTA11P, OR5A2, PAEP, RNA5SP86, OR51C4P, IGHVII.1.1, SHMT1P1, RACK1, RPL6, HSPA8, CSDE1, PMEPA1, HDLBP, RPS3A, RPS8, YWHAZ, RPS4X, RPL10, RPS3, ELOVL5, HNRNPK, SCD, SLC39A6, CALR, TXNIP, RPS27A, ACTG1, RPL3, RPL19, NUDT4, RPS25, LCP1, RPL24, The agent may further include a preparation for measuring the expression level of at least one gene selected from the group consisting of IDH1, DMXL1, NPNT, RDH11, MSMB, HMGB1, LENG8, PLPP1, HMGN2P46, RPL8, H3.3B, TBX3, SERP1, KLK3, RPS9, RPS23, ENDOD1, SPARCL1, TOMM20, SEMA3C, HLA.DRA, CRISP3, ITGB1, SEC11C, TACSTD2, KRT8, PNISR, DDX3X, PEBP1, and HSPD1, or a protein encoded by it.

[0019] 본 발명에서 상기 "LIM2, GTF2IP6, LINC02022, LILRP2, MYMX, LINC02730, RN7SL391P, RNA5SP468, LINC02209, PWWP4, DDR1.DT, KRT8P38, GAPDHP55, TRPC7.AS2, LINC01923, TSIX, KRTAP4.3, ANKRD34C.AS1, SNORD115.27, RPL18AP16, CYP2AB1P, SP7, GRM8.AS1, KASH5, CCDC63, TRPM5, SERPINA12, SCGB1D4, TBC1D3P6, ANKRD30A, LINC00993, PDLIM5, EEF1A1P5, RPL7, NKX3.1, HSP90B1, EEF1A1, RPS24, RPL4, TMPRSS2, HSP90AA1, TPD52, TPT1, HNRNPA1, HNRNPH1, EEF1A1P6, P4HB, NDRG1, FASN, B2M, ATP4A, PTH2, C1QL4, DSCR8, LINC02954, EIF4A1P9, CASC23, HES3, HTR3D, ATP2B3, SVOP, OR5AU1, CACNG2, PSG3, LINC02403, RN7SKP186, LHX1.DT, PDLIM1P1, GALP, KRT33A, OSBPL9P5, OR5AN1, GFY, RPL17P2 MIR5089, TMEM239, OTOAP1, CALML5, OR4K1, HSPD1P4, RN7SL219P, RPL17P11, SPRYD7P1, RNU6.949P, OR2Q1P, OR4K15, KRT8P51, ANKRD26P2, ANAPC10P1, LINC01517, MIR194.2HG, OR5B15P, RN7SKP205, LACRT, DNM1P5, KRTAP3.3, LINC01651, KRT26, KRT223P, INGX, B3GNT2P1, TUBA3GP, C10orf90, RPL15P20, XRCC6P3, LHX3, PCK1, LINC00661, C1QTNF1.AS1, ZAN, PSG1, NCOA4P4, BARHL1, RTP3, GSTA11P, OR5A2, PAEP, RNA5SP86, OR51C4P, IGHVII.1.1, SHMT1P1, RACK1, RPL6, HSPA8, CSDE1, PMEPA1, HDLBP, RPS3A, RPS8, YWHAZ, RPS4X, RPL10, RPS3, ELOVL5, HNRNPK, SCD, SLC39A6, CALR, TXNIP, RPS27A, ACTG1, RPL3, RPL19, NUDT4, RPS25, SFPQ, IGFBP5, RPL39, Information regarding the "genes RPS20, GLUD1, MTND2P28, HNRNPDL, RPS12, MTCO1P12, RPL12, COLCA1, LCP1, RPL24, IDH1, DMXL1, NPNT, RDH11, MSMB, HMGB1, LENG8, PLPP1, HMGN2P46, RPL8, H3.3B, TBX3, SERP1, KLK3, RPS9, RPS23, ENDOD1, SPARCL1, TOMM20, SEMA3C, HLA.DRA, CRISP3, ITGB1, SEC11C, TACSTD2, KRT8, PNISR, DDX3X, PEBP1, and HSPD1 or proteins encoded thereby" is registered in the NCBI (National Center for Biotechnology Information), and the disclosed Gene ID information of the said genes of the present invention is as follows, and to a person skilled in the art, it is understood that the present invention exerts the intended effects. Within the scope that is self-evident, it may include everything without limitation.

[0020] LIM2 (NCBI Gene ID: 3982), GTF2IP6 (NCBI Gene ID: 101927390), LINC02022 (NCBI Gene ID: 105376955), LILRP2 (NCBI Gene ID: 79166), MYMX (NCBI Gene ID: 101929726), LINC02730 (NCBI Gene ID: 107984414), RN7SL391P (NCBI Gene ID: 106481030), RNA5SP468 (NCBI Gene ID: 106480769), LINC02209 (NCBI Gene ID: 286135), PWWP4 (NCBI Gene ID: 728317), DDR1.DT (NCBI Gene ID: 414771), KRT8P38 (NCBI Gene ID: 100418799), GAPDHP55 (NCBI Gene ID: 100421324), TRPC7.AS2 (NCBI Gene ID: 106478968), LINC01923 (NCBI Gene ID: 101927619), TSIX (NCBI Gene ID: 9383), KRTAP4.3 (NCBI Gene ID: 85290), ANKRD34C.AS1 (NCBI Gene ID: 729911), SNORD115.27 (NCBI Gene ID: 100036564), RPL18AP16 (NCBI Gene ID: 347544), CYP2AB1P (NCBI Gene ID: 647265), SP7 (NCBI Gene ID: 121340), GRM8.AS1 (NCBI Gene ID: 101928333), KASH5 (NCBI Gene ID: 147872), CCDC63 (NCBI Gene ID: 160762), TRPM5 (NCBI Gene ID: 29850), SERPINA12 (NCBI Gene ID: 145264), SCGB1D4 (NCBI Gene ID: 404552), TBC1D3P6 (NCBI Gene ID: 101928566),ANKRD30A (NCBI Gene ID: 91074), LINC00993 (NCBI Gene ID: 101929520), PDLIM5 (NCBI Gene ID: 10611), EEF1A1P5 (NCBI Gene ID: 158078), RPL7 (NCBI Gene ID: 6129), NKX3.1 (NCBI Gene ID: 4824), HSP90B1 (NCBI Gene ID: 7184), EEF1A1 (NCBI Gene ID: 1915), RPS24 (NCBI Gene ID: 6229), RPL4 (NCBI Gene ID: 6124), TMPRSS2 (NCBI Gene ID: 7113), HSP90AA1 (NCBI Gene ID: 3320), TPD52 (NCBI Gene ID: 7163), TPT1 (NCBI Gene ID: 7178), HNRNPA1 (NCBI Gene ID: 3178), HNRNPH1 (NCBI Gene ID: 3187), EEF1A1P6 (NCBI Gene ID: 221838), P4HB (NCBI Gene ID: 5034), NDRG1 (NCBI Gene ID: 10397), FASN (NCBI Gene ID: 2194), B2M (NCBI Gene ID: 567), ATP4A (NCBI Gene ID: 495), PTH2 (NCBI Gene ID: 113091), C1QL4 (NCBI Gene ID: 338761), DSCR8 (NCBI Gene ID: 84677), LINC02954 (NCBI Gene ID: 123466205), EIF4A1P9 (NCBI Gene ID: 642746), CASC23 (NCBI Gene ID: 103581031), HES3 (NCBI Gene ID: 390992), HTR3D (NCBI Gene ID: 200909), ATP2B3 (NCBI Gene ID: 492), SVOP (NCBI Gene ID: 55530), OR5AU1 (NCBI Gene ID: 390445),CACNG2 (NCBI Gene ID: 10369), PSG3 (NCBI Gene ID: 5671), LINC02403 (NCBI Gene ID: 105369785), RN7SKP186 (NCBI Gene ID: 106480692), LHX1.DT (NCBI Gene ID: 102723471), PDLIM1P1 (NCBI Gene ID: 326616), GALP (NCBI Gene ID: 85569), KRT33A (NCBI Gene ID: 3883), OSBPL9P5 (NCBI Gene ID: 106480232), OR5AN1 (NCBI Gene ID: 390195), GFY (NCBI Gene ID: 100507003), RPL17P2 (NCBI Gene ID: 652974), MIR5089 (NCBI Gene ID: 100847067), TMEM239 (NCBI Gene ID: 100288797), OTOAP1 (NCBI Gene ID: 653786), CALML5 (NCBI Gene ID: 51806), OR4K1 (NCBI Gene ID: 79544), HSPD1P4 (NCBI Gene ID: 644745), RN7SL219P (NCBI Gene ID: 106479302), RPL17P11 (NCBI Gene ID: 100270937), SPRYD7P1 (NCBI Gene ID: 100130843), RNU6.949P (NCBI Gene ID: 106481925), OR2Q1P (NCBI Gene ID: 346524), OR4K15 (NCBI Gene ID: 81127), KRT8P51 (NCBI Gene ID: 106480676), ANKRD26P2 (NCBI Gene ID: 646929), ANAPC10P1 (NCBI Gene ID: 729198), LINC01517 (NCBI Gene ID: 101929218), MIR194.2HG (NCBI Gene ID: 105369343), OR5B15P (NCBI Gene ID: 81215),RN7SKP205 (NCBI Gene ID: 106479186), LACRT (NCBI Gene ID: 90070), DNM1P5 (NCBI Gene ID: 728770), KRTAP3.3 (NCBI Gene ID: 85293), LINC01651 (NCBI Gene ID: 105372944), KRT26 (NCBI Gene ID: 353288), KRT223P (NCBI Gene ID: 643115), INGX (NCBI Gene ID: 27160), B3GNT2P1 (NCBI Gene ID: 100422469), TUBA3GP (NCBI Gene ID: 645348), C10orf90 (NCBI Gene ID: 118611), RPL15P20 (NCBI Gene ID: 646672), XRCC6P3 (NCBI Gene ID: 127086), LHX3 (NCBI Gene ID: 8022), PCK1 (NCBI Gene ID: 5105), LINC00661 (NCBI Gene ID: 126536), C1QTNF1.AS1 (NCBI Gene ID: 100507410), ZAN (NCBI Gene ID: 7455), PSG1 (NCBI Gene ID: 5669), NCOA4P4 (NCBI Gene ID: 642262), BARHL1 (NCBI Gene ID: 56751), RTP3 (NCBI Gene ID: 83597), GSTA11P (NCBI Gene ID: 647175), OR5A2 (NCBI Gene ID: 219981), PAEP (NCBI Gene ID: 5047), RNA5SP86 (NCBI Gene ID: 100873319), OR51C4P (NCBI Gene ID: 390041), IGHVII.1.1 (NCBI Gene ID: 28377), SHMT1P1 (NCBI Gene ID: 6471), RACK1 (NCBI Gene ID: 10399), RPL6 (NCBI Gene ID: 6128), HSPA8 (NCBI Gene ID: 3312),CSDE1 (NCBI Gene ID: 7812), PMEPA1 (NCBI Gene ID: 56937), HDLBP (NCBI Gene ID: 3069), RPS3A (NCBI Gene ID: 6189), RPS8 (NCBI Gene ID: 6202), YWHAZ (NCBI Gene ID: 7534), RPS4X (NCBI Gene ID: 6191), RPL10 (NCBI Gene ID: 6134), RPS3 (NCBI Gene ID: 6188), ELOVL5 (NCBI Gene ID: 60481), HNRNPK (NCBI Gene ID: 3190), SCD (NCBI Gene ID: 6319), SLC39A6 (NCBI Gene ID: 25800), CALR (NCBI Gene ID: 811), TXNIP (NCBI Gene ID: 10628), RPS27A (NCBI Gene ID: 6233), ACTG1 (NCBI Gene ID: 71), RPL3 (NCBI Gene ID: 6122), RPL19 (NCBI Gene ID: 6143), NUDT4 (NCBI Gene ID: 11163), RPS25 (NCBI Gene ID: 6230), XBP1 (NCBI Gene ID: 7494), RPL37A (NCBI Gene ID: 6168), TM9SF3 (NCBI Gene ID: 56889), LMAN1 (NCBI Gene ID: 3998), GOLM1 (NCBI Gene ID: 51280), TTC3 (NCBI Gene ID: 7267), ACSL3 (NCBI Gene ID: 2181), APP (NCBI Gene ID: 351), FOXA1 (NCBI Gene ID: 3169), HSPA5 (NCBI Gene ID: 3309), DDX5 (NCBI Gene ID: 1655), SRSF6 (NCBI Gene ID: 6431), SFPQ (NCBI Gene ID: 6421), IGFBP5 (NCBI Gene ID: 3488),RPL39 (NCBI Gene ID: 6170), RPS20 (NCBI Gene ID: 6224), GLUD1 (NCBI Gene ID: 2746), MTND2P28 (NCBI Gene ID: 100652939), HNRNPDL (NCBI Gene ID: 9987), RPS12 (NCBI Gene ID: 6206), MTCO1P12 (NCBI Gene ID: 107075141), RPL12 (NCBI Gene ID: 6136), COLCA1 (NCBI Gene ID: 399948), LCP1 (NCBI Gene ID: 3936), RPL24 (NCBI Gene ID: 6152), IDH1 (NCBI Gene ID: 3417), DMXL1 (NCBI Gene ID: 1657), NPNT (NCBI Gene ID: 255743), RDH11 (NCBI Gene ID: 51109), MSMB (NCBI Gene ID: 4477), HMGB1 (NCBI Gene ID: 3146), LENG8 (NCBI Gene ID: 114823), PLPP1 (NCBI Gene ID: 8611), HMGN2P46 (NCBI Gene ID: 283651), RPL8 (NCBI Gene ID: 6132), H3.3B (NCBI Gene ID: 3021), TBX3 (NCBI Gene ID: 6926), SERP1 (NCBI Gene ID: 27230), KLK3 (NCBI Gene ID: 354), RPS9 (NCBI Gene ID: 6203), RPS23 (NCBI Gene ID: 6228), ENDOD1 (NCBI Gene ID: 23052), SPARCL1 (NCBI Gene ID: 8404), TOMM20 (NCBI Gene ID: 9804), SEMA3C (NCBI Gene ID: 10512), HLA.DRA (NCBI Gene ID: 3122), CRISP3 (NCBI Gene ID: 10321), ITGB1 (NCBI Gene ID: 3688),SEC11C (NCBI Gene ID: 90701), TACSTD2 (NCBI Gene ID: 4070), KRT8 (NCBI Gene ID: 3856), PNISR (NCBI Gene ID: 25957), DDX3X (NCBI Gene ID: 1654), PEBP1 (NCBI Gene ID: 5037) and HSPD1 (NCBI Gene ID: 3329),

[0021] In this invention, the terms "drug" or "therapeutic agent" may be used interchangeably, and the drug refers to a drug that has an anticancer effect by killing cancer cells as well as cancer stem cells.

[0022] In the present invention, the term "cancer" may be one or more selected from the group consisting of prostate cancer, colorectal cancer, breast cancer, mammary gland cancer, glioma, thyroid cancer, parathyroid cancer, lung cancer, liver cancer, pancreatic cancer, head and neck cancer, stomach cancer, urothelial carcinoma, kidney cancer, testicular cancer, penile cancer, cervical cancer, ovarian cancer, endometrial cancer, fallopian tube cancer, uterine cancer, vaginal cancer, melanoma, skin cancer, blood cancer, bone cancer, brain cancer, endocrine cancer, ureteral cancer, urethral cancer, bronchial cancer, bladder cancer, bone marrow cancer, leukemia, cervical cancer, intestinal cancer, esophageal cancer, sarcoma, tongue cancer, lymphoma, and neuroblastoma, and specifically may be prostate cancer, but is not limited thereto.

[0023] In this invention, "prostate cancer" refers to a malignant tumor arising in the prostate, a male reproductive organ, and is classified as a condition in which abnormal cells proliferate within prostate tissue. The genetic and molecular profiles of prostate cancer vary significantly from patient to patient. Sensitivity to specific targeted therapies differs depending on the subtype of prostate cancer, and individual genetic characteristics lead to variations in AR (Androgen receptor) mutations, overexpression, and activation of other signaling pathways. Consequently, responses to or resistance to hormone therapy or chemotherapy differ, posing a challenge in selecting therapeutic drugs. For example, it is known that resistance to hormone therapy may develop over time in metastatic prostate cancer. Furthermore, it is reported that patients with specific gene mutations (e.g., BRCA mutations) have a higher likelihood of responding to targeted therapies such as PARP inhibitors, making them particularly useful for patients who exhibit resistance to standard hormone therapy. For the effective treatment of prostate cancer, it is of paramount importance to predict the prognosis prior to treatment through drug response. Meanwhile, resistance to PARP inhibitors can arise from various complex mechanisms other than DNA repair pathways, resulting in a lack of research on the therapeutic effects of PARP inhibitors in prostate cancer.

[0024] In the present invention, the "drug" is a drug having a mechanism for killing cancer cells and may include, but is not limited to, a PARP (Poly ADP-Ribose Polymerase) inhibitor.

[0025] In the present invention, the "PARP (Poly ADP-Ribose Polymerase) inhibitor" is a targeted anticancer agent that kills cancer cells by interfering with DNA repair in cancer cells. It acts through a mechanism that interferes with DNA single-strand damage repair by inhibiting PARP1 and PARP2 enzymes, and it is known that cancer cells with BRCA1 / 2 mutations are particularly sensitive to the drug when there is a defect in homologous recombination repair (HRR). Although it is used for the treatment of ovarian cancer, breast cancer, prostate cancer, pancreatic cancer, etc., PARP inhibitors show great efficacy in cancer patients with specific gene defects, and treatment responsiveness varies significantly depending on individual genetic characteristics, so there is a need to determine responsiveness to the drug early before treatment.

[0026] In the present invention, the term "inhibitor" refers to a substance that causes a decrease in the activity or expression of the PARP1, PARP2, or PARP3 genes. It refers to a substance that reduces the activity or expression of these genes to a level that not only renders their activity or expression undetectable or insignificant, but also significantly improves the repair of DNA damage caused by these genes and the resulting survival of cancer cells, thereby inducing apoptosis in cancer cells.

[0027] In the present invention, the term "decrease in expression" may mean a state in which the expression level of these genes at the gene level (e.g., DNA or mRNA) or at the level of the protein they encode is reduced by, for example, 20% or more compared to the control group, more specifically, a state in which it is reduced by 30% or more, and more specifically, a state in which it is reduced by 40% or more.

[0028] In the present invention, the term "decrease in activity" refers to a significant, measurable reduction in the intrinsic in vivo function of these genes or the proteins they encode compared to a control group; specifically, it means a reduction in activity to the extent that the induction of apoptosis in cancer cells within the individual can be significantly improved or restored. The decrease in activity includes not only a simple reduction in function but also ultimate inhibition of activity resulting from a decrease in stability.

[0029] In the present invention, the PARP inhibitor may include, for example, a CRISPR system comprising shRNA, siRNA, miRNA, ribozyme, PNA (peptide nucleic acids), antisense oligonucleotide, and guide RNA that recognizes a target gene, which inhibits the expression of PARP1, PARP2, or PARP3 at the gene level, the nucleotide sequence and the amino acid sequence of the encoding protein of which are already known in the art; as well as antibodies or aptamers that inhibit their expression at the protein level, and small molecule compounds, peptides, and natural products that inhibit their activity, but are not limited thereto, and any possible means of inhibition at the gene and protein levels may be used.

[0030] In the present invention, the PARP inhibitor may be a nucleic acid molecule that inhibits the expression of the PARP1, PARP2, or PARP3 gene; or an antibody that specifically binds to the protein encoded by the gene, its antigen-binding fragment, or an aptamer.

[0031] In the present invention, the term "nucleic acid molecule" comprehensively includes DNA (gDNA and cDNA) and RNA molecules, and nucleotides, which are the basic building blocks of nucleic acid molecules, include not only natural nucleotides but also analogues in which the sugar or base portion is modified (Scheit, Nucleotide Analogs, John Wiley, New York (1980); Uhlman and Peyman, Chemical Reviews, 90:543-584 (1990)).

[0032] In the present invention, the term "nucleic acid molecule that inhibits expression" refers to a nucleic acid molecule that specifically recognizes a target gene by including a complementary nucleic acid sequence that can hybridize with the target gene and causes a modification on the nucleotide structure that causes a decrease in its function, and includes, for example, the shRNA, siRNA, miRNA, ribozymes, PNA, antisense oligonucleotides, and gRNA included in the CRISPR system described above.

[0033] In the present invention, the term "complementary" means sufficiently complementary to the extent that a nucleic acid molecule for expression inhibition selectively hybridizes to a target nucleic acid sequence under predetermined annealing or hybridization conditions, and encompasses both substantially complementary and perfectly complementary, preferably meaning perfectly complementary.

[0034] In the present invention, the term "substantially complementary sequence" includes not only sequences that are completely identical, but also sequences that are partially incompatible with the sequence to the extent that sequence-specific hybridization can occur upon annealing to a specific sequence.

[0035] In the present invention, the "shRNA (small hairpin RNA)" refers to a single strand of 50 to 70 nucleotides forming a stem-loop structure in vivo, and means an RNA sequence that creates a tight hairpin structure to suppress the expression of a target gene through RNA interference. Typically, a long RNA of 19 to 29 nucleotides forms base pairs complementarily on both sides of a loop region of 5 to 10 nucleotides to form a double-stranded stem, and is transfected into a cell via a vector containing a U6 promoter to ensure constant expression, and is usually transferred to a daughter cell to ensure that the suppression of the target gene's expression is inherited.

[0036] In the present invention, the "siRNA" refers to a short double-stranded RNA capable of inducing RNAi (RNA interference) phenomena through the cleavage of a specific mRNA. It consists of a sense RNA strand having a sequence homologous to the mRNA of a target gene and an antisense RNA strand having a sequence complementary thereto. The total length is 10 to 100 bases, preferably 15 to 80 bases, and most preferably 20 to 70 bases. Both blunt and cohesive ends are possible as long as they can inhibit the expression of the target gene through the RNAi effect. For the cohesive end structure, both a structure with a protruding 3-terminal end and a structure with a protruding 5-terminal end are possible.

[0037] In the present invention, the "miRNA (microRNA)" refers to a single-stranded RNA molecule that is not expressed within a cell, has a short stem-loop structure, and inhibits target gene expression through complementary binding to the mRNA of the target gene.

[0038] In the present invention, the term "ribozyme" refers to a type of RNA molecule that functions like an enzyme by recognizing a specific RNA base sequence and cleaving it. A ribozyme consists of a region that specifically binds to the base sequence complementary to the target mRNA strand and a region that cleaves the target RNA.

[0039] In the present invention, the term "PNA (Peptide nucleic acid)" refers to a molecule that possesses the properties of both nucleic acids and proteins and is capable of binding complementarily to DNA or RNA. PNA is not found in nature but is synthesized artificially through chemical methods; it regulates the expression of target genes by forming a double strand through hybridization with natural nucleic acids of complementary base sequences.

[0040] In the present invention, the "antisense oligonucleotide" refers to a nucleotide sequence that is complementary to the sequence of a specific mRNA and binds to the complementary sequence within the target mRNA to inhibit essential activities for its translation into protein, translocation into the cytoplasm, maturation, or any other overall biological function. Antisense oligonucleotides may be modified at one or more bases, sugars, or backbone positions to enhance efficacy (De Mesmaeker et al., Curr Opin Struct Biol., 5(3):343-55, 1995). The oligonucleotide backbone may be modified to phosphorothioates, phosphotriesters, methyl phosphonates, short-chain alkyls, cycloalkyls, short-chain heteroatomics, heterocyclic sugar sholphonates, etc.

[0041] In the present invention, the "gRNA (guideRNA)" refers to an RNA molecule used in a gene editing system that specifically cleaves a recognized site by recognizing a target gene and inducing a nuclease. A representative example of such a gene editing system is the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) system.

[0042] The nucleic acid molecule of the present invention can suppress the expression of PARP1, PARP2, or PARP3 at the genetic level by expressing it within an individual (e.g., a cancer patient).

[0043] In the present invention, the term "to express" means that a gene becomes replicable within an individual cell as an extrachromosomal factor or through the completion of chromosomal integration by artificially introducing it using a gene carrier to cause an individual to express an exogenous gene or to increase the natural expression level of an endogenous gene. Accordingly, the term "expression" has the same meaning as "transformation," "transfection," or "transduction."

[0044] In the present invention, the term "gene delivery system" refers to any means of transporting a gene into a cell, and gene delivery has the same meaning as the transduction of a gene into the cell. At the tissue level, the term gene delivery has the same meaning as the spread of a gene. Accordingly, the gene delivery system of the present invention may be described as a gene transduction system and a gene spread system.

[0045] The PARP inhibitor of the present invention may be a specific antibody that inhibits the activity of the PARP1, PARP2, or PARP3 genes listed above at the protein level. The antibody that specifically recognizes the protein encoded by these genes is a polyclonal or monoclonal antibody, preferably a monoclonal antibody.

[0046] In the present invention, antibodies may be prepared by methods commonly practiced in the art, for example, by the fusion method (Kohler and Milstein, European Journal of Immunology, 6:511-519 (1976)), the recombinant DNA method (U.S. Patent No. 4,816,567), or the phage antibody library method (Clackson et al, Nature, 352:624-628 (1991) and Marks et al, J. Mol. Biol., 222:58, 1-597 (1991)). General processes for antibody preparation are described in detail in Harlow, E. and Lane, D., Using Antibodies: A Laboratory Manual, Cold Spring Harbor Press, New York, 1999; and Zola, H., Monoclonal Antibodies: A Manual of Techniques, CRC Press, Inc., Boca Raton, Florida, 1984.

[0047] In the present invention, the "antigen binding fragment" refers to a part of the polypeptide capable of binding to an antigen within the entire structure of the immunoglobulin, and includes, for example, F(ab')2, Fab', Fab, Fv, and scFv, but is not limited thereto.

[0048] In this invention, the term "specifically binding" has the same meaning as "specifically recognizing" and refers to the specific interaction between an antigen and an antibody (or a fragment thereof) through an immunological reaction.

[0049] The present invention may inhibit the activity of a target protein by using an aptamer that specifically binds to the target protein instead of an antibody. In the present invention, the term "aptamer" refers to a single-stranded nucleic acid (RNA or DNA) molecule or peptide molecule that binds to a specific target substance with high affinity and specificity. General information regarding aptamers is disclosed in detail in Hoppe-Seyler F, Butz K "Peptide aptamers: powerful new tools for molecular medicine". J Mol Med. 78(8):426-30(2000); and Cohen BA, Colas P, Brent R. "An artificial cell-cycle inhibitor isolated from a combinatorial library". Proc Natl Acad Sci USA. 95(24):14272-7(1998).

[0050] In addition, the inhibitors used in the present invention also include small molecule inhibitors for the PARP1, PARP2, or PARP3 genes. Small molecule compounds known in the art may also be used.

[0051] In the present invention, the PARP inhibitor may be at least one selected from the group consisting of olaparib, niraparib, rucaparib, talazoparib, and veliparib, and specifically may be olaparib or niraparib, but is not limited to the drugs mentioned above as long as they correspond to drugs that act through the same mechanism as the PARP inhibitor.

[0052] In the present invention, the term "drug responsiveness" refers to the degree of efficacy of drug treatment and may be used interchangeably with "therapeutic responsiveness." For example, when used in relation to the treatment of cancer patients, the terms "increased responsiveness" or "good responsiveness" may refer to an increase in the efficacy of the drug when measured using any method known in the art. As another example, the response of a cancer patient to a drug may be characterized as a complete or partial response. As yet another example, the increased responsiveness of a cancer patient to a drug may be characterized as overall survival, disease-free survival, target response rate, time to tumor progression, progression-free survival, or time to treatment failure. Good therapeutic responsiveness may mean that the effect of the drug does not decrease when the drug is administered repeatedly in a fixed dose, or that overall survival, disease-free survival, rate of target response, time to tumor progression, progression-free survival, or time to treatment failure increases; conversely, for patients with poor therapeutic responsiveness, it may mean that the dosage or frequency of use must be increased to achieve the same effect experienced previously, or that even if the same dose of the substance is administered, the same effect is not achieved, or that overall survival, disease-free survival, rate of target response, time to tumor progression, progression-free survival, or time to treatment failure decreases.

[0053] In the present invention, "prediction" refers to the act of a patient predicting the course and outcome of a disease in advance regarding a drug or a set of drugs. More specifically, it is defined as a broad concept that includes determining susceptibility to a drug or determining the therapeutic responsiveness of cancer to the said drug. It may be interpreted to mean all acts of predicting drug responsiveness before and after treatment by comprehensively considering the patient's condition, which varies according to their genetic state.

[0054] For the purposes of the present invention, the prediction of drug responsiveness may be interpreted as the act of predicting in advance whether drug treatment, specifically the therapeutic responsiveness of a PARP inhibitor or whether resistance to a PARP inhibitor develops, or the act of appropriately selecting whether to use the drug based thereon.

[0055] The agent for measuring the expression level of the gene in the composition of the present invention may include a primer that specifically binds to a nucleic acid molecule of the gene or a probe that specifically binds to a nucleic acid molecule of the gene, but is not limited thereto.

[0056] In the present invention, the "primer" is a fragment that recognizes a target gene sequence and includes a forward and reverse primer pair, but preferably is a primer pair that provides analysis results having specificity and sensitivity. High specificity can be conferred when the nucleic acid sequence of the primer is a sequence that is inconsistent with the non-target sequence present in the sample, so that it amplifies only the target gene sequence containing the complementary primer binding site and does not induce non-specific amplification.

[0057] In the present invention, the term "probe" refers to a substance capable of specifically binding to a target substance to be detected within a sample, and means a substance capable of specifically confirming the presence of the target substance within the sample through said binding. The type of probe is not limited to substances commonly used in the industry, but preferably may be PNA (peptide nucleic acid), LNA (locked nucleic acid), peptide, polypeptide, protein, RNA, or DNA, and most preferably PNA. More specifically, the probe may be a biomaterial derived from an organism or similar, or manufactured in vitro, and may be, for example, enzymes, proteins, antibodies, microorganisms, animal and plant cells and organs, nerve cells, DNA, and RNA; DNA may include cDNA, genomic DNA, and oligonucleotides; RNA may include genomic RNA, mRNA, and oligonucleotides; and examples of proteins may include antibodies, antigens, enzymes, peptides, etc.

[0058] In the present invention, "LNA (Locked nucleic acids)" refers to nucleic acid analogs containing a 2'-O, 4'-C methylene bridge [J Weiler, J Hunziker and J Hall Gene Therapy (2006) 13, 496.502]. LNA nucleosides contain common nucleic acid bases of DNA and RNA and can form base pairs according to the Watson-Crick base pairing rule. However, due to the 'locking' of the molecule caused by the methylene bridge, LNAs are unable to form an ideal shape in Watson-Crick bonding. When LNAs are included in DNA or RNA oligonucleotides, LNAs can pair more quickly with complementary nucleotide chains, thereby increasing the stability of the double helix.

[0059] 본 발명에 따른 LIM2, GTF2IP6, LINC02022, LILRP2, MYMX, LINC02730, RN7SL391P, RNA5SP468, LINC02209, PWWP4, DDR1.DT, KRT8P38, GAPDHP55, TRPC7.AS2, LINC01923, TSIX, KRTAP4.3, ANKRD34C.AS1, SNORD115.27, RPL18AP16, CYP2AB1P, SP7, GRM8.AS1, KASH5, CCDC63, TRPM5, SERPINA12, SCGB1D4, TBC1D3P6, ANKRD30A, LINC00993, PDLIM5, EEF1A1P5, RPL7, NKX3.1, HSP90B1, EEF1A1, RPS24, RPL4, TMPRSS2, HSP90AA1, TPD52, TPT1, HNRNPA1, HNRNPH1, EEF1A1P6, P4HB, NDRG1, FASN, B2M, ATP4A, PTH2, C1QL4, DSCR8, LINC02954, EIF4A1P9, CASC23, HES3, HTR3D, ATP2B3, SVOP, OR5AU1, CACNG2, PSG3, LINC02403, RN7SKP186, LHX1.DT, PDLIM1P1, GALP, KRT33A, OSBPL9P5, OR5AN1, GFY, RPL17P2, MIR5089, TMEM239 OTOAP1, CALML5, OR4K1, HSPD1P4, RN7SL219P, RPL17P11, SPRYD7P1, RNU6.949P, OR2Q1P, OR4K15, KRT8P51, ANKRD26P2, ANAPC10P1, LINC01517, MIR194.2HG, OR5B15P, RN7SKP205, LACRT, DNM1P5, KRTAP3.3, LINC01651, KRT26, KRT223P, INGX, B3GNT2P1, TUBA3GP, C10orf90, RPL15P20, XRCC6P3, LHX3, PCK1, LINC00661, C1QTNF1.AS1, ZAN, PSG1, NCOA4P4, BARHL1, RTP3, GSTA11P, OR5A2, PAEP, RNA5SP86, OR51C4P, IGHVII.1.1, SHMT1P1, RACK1, RPL6, HSPA8, CSDE1, PMEPA1, HDLBP, RPS3A, RPS8, YWHAZ, RPS4X, RPL10, RPS3, ELOVL5, HNRNPK, SCD, SLC39A6, CALR, TXNIP, RPS27A, ACTG1, RPL3, RPL19, NUDT4, RPS25, SFPQ, IGFBP5, RPL39, Since the information on the genes RPS20, GLUD1, MTND2P28, HNRNPDL, RPS12, MTCO1P12, RPL12, COLCA1, LCP1, RPL24, IDH1, DMXL1, NPNT, RDH11, MSMB, HMGB1, LENG8, PLPP1, HMGN2P46, RPL8, H3.3B, TBX3, SERP1, KLK3, RPS9, RPS23, ENDOD1, SPARCL1, TOMM20, SEMA3C, HLA.DRA, CRISP3, ITGB1, SEC11C, TACSTD2, KRT8, PNISR, DDX3X, PEBP1, and HSPD1, or the proteins encoded by them, is known, a person skilled in the art would be able to easily design primers or probes that specifically bind to said genes based on this information.

[0060] The preparation for measuring the expression level of the protein in the composition of the present invention may include one or more selected from the group consisting of an antibody or an antigen-binding fragment thereof that specifically binds to the protein; an oligopeptide; a ligand; PNA (peptide nucleic acid); and an aptamer, but is not limited thereto.

[0061] In the present invention, the term "antibody" refers to a substance that specifically binds to an antigen and causes an antigen-antibody reaction. For the purposes of the present invention, an antibody means an antibody that specifically binds to the protein. The antibodies of the present invention include polyclonal antibodies, monoclonal antibodies, and recombinant antibodies. The antibodies can be easily manufactured using techniques widely known in the art. For example, polyclonal antibodies can be produced by a method widely known in the art that includes the process of injecting an antigen of the protein into an animal and collecting blood from the animal to obtain serum containing antibodies. Such polyclonal antibodies can be produced from any animal, such as a goat, rabbit, sheep, monkey, horse, pig, cattle, or dog. In addition, monoclonal antibodies may be prepared using the hybridoma method (see Kohler and Milstein (1976) European Journal of Immunology 6:511-519), which is widely known in the industry, or phage antibody library technology (see Clackson et al, Nature, 352:624-628, 1991; Marks et al, J. Mol. Biol., 222:58, 1-597, 1991). Antibodies prepared by the above methods may be separated and purified using methods such as gel electrophoresis, dialysis, salt precipitation, ion exchange chromatography, and affinity chromatography. Furthermore, the antibodies of the present invention comprise not only a complete form having two full-length light chains and two full-length heavy chains, but also functional fragments of the antibody molecule. A functional fragment of an antibody molecule refers to a fragment that possesses at least an antigen-binding function, and includes Fab, F(ab'), F(ab')2, and Fv.

[0062] In the present invention, the "antigen binding fragment" refers to a part of the polypeptide capable of binding to an antigen within the entire structure of the immunoglobulin, and includes, for example, F(ab')2, Fab', Fab, Fv, and scFv, but is not limited thereto.

[0063] In this invention, the term "specifically binding" has the same meaning as "specifically recognizing" and refers to the specific interaction between an antigen and an antibody (or a fragment thereof) through an immunological reaction.

[0064] In the present invention, the "oligopeptide" is a peptide composed of 2 to 20 amino acids and may include dipeptides, tripeptides, tetrapeptides, and pentapeptides, but is not limited thereto.

[0065] In the present invention, the "PNA (Peptide Nucleic Acid)" refers to an artificially synthesized polymer similar to DNA or RNA, which was first introduced in 1991 by Professors Nielsen, Egholm, Berg, and Buchardt of the University of Copenhagen, Denmark. While DNA has a phosphate-ribose sugar backbone, PNA has a repeating N-(2-aminoethyl)-glycine backbone connected by peptide bonds, which significantly increases its binding affinity and stability to DNA or RNA, and is therefore used in molecular biology, diagnostic analysis, and antisense therapy. PNA is disclosed in detail in the literature [Nielsen PE, Egholm M, Berg RH, Buchardt O (December 1991). "Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide". Science 254 (5037): 1497-1500].

[0066] In the present invention, the "aptamer" is an oligonucleotide or peptide molecule, and general information regarding aptamers is disclosed in detail in the literature [Bock LC et al., Nature 355(6360):5646(1992); Hoppe-Seyler F, Butz K "Peptide aptamers: powerful new tools for molecular medicine". J Mol Med. 78(8):42630(2000); Cohen BA, Colas P, Brent R. "An artificial cell-cycle inhibitor isolated from a combinatorial library". Proc Natl Acad Sci USA. 95(24): 142727(1998)].

[0067]

[0068] According to another embodiment of the present invention, the invention relates to a kit for predicting drug responsiveness comprising a composition of the present invention.

[0069] In the present invention, the "kit" refers to a tool capable of evaluating the expression level of a biomarker by labeling a probe or antibody that specifically binds to a biomarker component with a detectable label. It includes not only direct labeling of a detectable substance related to a probe or antibody through reaction with a substrate, but also indirect labeling in which a label that develops color through reactivity with another directly labeled reagent is conjugated. It may include a color-developing substrate solution, washing solution, and other solutions that react with the label for color development, and may be manufactured to include the reagent components used. In the present invention, the kit may be a kit containing essential elements necessary for performing RT-PCR, and in addition to specific primer pairs for the marker gene, it may include test tubes, reaction buffer, deoxyribonucleotides (dNTPs), Taq polymerase, reverse transcriptase, DNase, RNase inhibitor, sterile water, etc. Furthermore, the kit may be a kit for detecting genes for diagnosing anticancer drug resistance that includes essential elements necessary for performing DNA chip analysis. A DNA chip kit comprises a substrate to which cDNA corresponding to a gene or a fragment thereof is attached as a probe, and the substrate may comprise cDNA corresponding to a quantitative control gene or a fragment thereof. The kit of the present invention is not limited to those known in the art.

[0070] In the present invention, the kit may be an RT-PCR kit, a DNA chip kit, an ELISA kit, a protein chip kit, a rapid kit, or an MRM (Multiple reaction monitoring) kit, but is not limited thereto.

[0071] The kit of the present invention may further include one or more other component compositions, solutions, or devices suitable for the analysis method. For example, the kit of the present invention may further include essential elements necessary to perform a reverse transcription polymerase chain reaction. The reverse transcription polymerase chain reaction kit includes a primer pair specific to a gene encoding a marker protein. The primer is a nucleotide having a sequence specific to the nucleic acid sequence of the gene and may have a length of about 7 bp to 50 bp, more preferably about 10 bp to 30 bp. It may also include a primer specific to the nucleic acid sequence of a control gene. Furthermore, the reverse transcription polymerase chain reaction kit may include a test tube or other suitable container, a reaction buffer (with varying pH and magnesium concentration), deoxyribonucleotides (dNTPs), enzymes such as Taq-polymerase and reverse transcriptase, DNase, RNase inhibitor DEPC-water, sterile water, etc.

[0072] In addition, the kit of the present invention may include essential elements necessary for performing DNA chip operations. The DNA chip kit may include a substrate to which cDNA or oligonucleotides corresponding to a gene or a fragment thereof are attached, and reagents, preparations, enzymes, etc., for producing fluorescently labeled probes. Additionally, the substrate may include cDNA or oligonucleotides corresponding to a control gene or a fragment thereof.

[0073] In addition, the kit of the present invention may include essential elements necessary for performing ELISA. The ELISA kit includes an antibody specific to the protein. The antibody is a monoclonal antibody, a polyclonal antibody, or a recombinant antibody that has high specificity and affinity for the marker protein and has little cross-reactivity with other proteins. Additionally, the ELISA kit may include an antibody specific to a control protein. Furthermore, the ELISA kit may include reagents capable of detecting the bound antibody, such as a labeled secondary antibody, chromophores, an enzyme (e.g., conjugated with the antibody) and its substrate, or other substances capable of binding to the antibody.

[0074] In the kit of the present invention, the immobilizer for the antigen-antibody binding reaction may be a nitrocellulose membrane, a PVDF membrane, a well plate synthesized from polyvinyl resin or polystyrene resin, a glass slide glass, etc., but is not limited thereto.

[0075] In addition, the label of the secondary antibody in the kit of the present invention is preferably a conventional chromogenic agent that produces a color reaction, and labels such as fluorescein and dyes such as HRP (horseradish peroxidase), alkaline phosphatase, colloid gold, FITC (poly L-lysine-fluorescein isothiocyanate), and RITC (rhodamine-B-isothiocyanate) may be used, but are not limited thereto.

[0076] In addition, the chromogenic substrate for inducing color development in the kit of the present invention is preferably used according to the label that performs the color reaction, and TMB (3,3',5,5'-tetramethylbezidine), ABTS [2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)], OPD (o-phenylenediamine), etc. may be used. At this time, it is more preferable that the chromogenic substrate be provided in a state dissolved in a buffer solution (0.1 M NaAc, pH 5.5). A chromogenic substrate such as TMB is degraded by HRP used as a label for the secondary antibody conjugate to produce a chromogenic precipitate, and the presence or absence of the marker proteins is detected by visually confirming the degree of precipitation of this chromogenic precipitate.

[0077] In the kit of the present invention, the washing solution preferably comprises phosphate buffer solution, NaCl, and Tween 20, and a buffer solution (PBST) composed of 0.02 M phosphate buffer solution, 0.13 M NaCl, and 0.05% Tween 20 is more preferably used. After the antigen-antibody binding reaction, a secondary antibody is reacted with the antigen-antibody conjugate, and then an appropriate amount of the washing solution is added to the immobilizer to wash 3 to 6 times. A sulfuric acid solution (H2SO4) may preferably be used as the reaction stopping solution.

[0078]

[0079] According to another embodiment of the present invention, the invention relates to a method for providing information for predicting drug responsiveness.

[0080] The above method of the present invention, with respect to a biological sample isolated from the target individual, LIM2, GTF2IP6, LINC02022, LILRP2, MYMX, LINC02730, RN7SL391P, RNA5SP468, LINC02209, PWWP4, DDR1.DT, KRT8P38, GAPDHP55, TRPC7.AS2, LINC01923, TSIX, KRTAP4.3, ANKRD34C.AS1, SNORD115.27, RPL18AP16, CYP2AB1P, SP7, GRM8.AS1, KASH5, CCDC63, TRPM5, SERPINA12, SCGB1D4, TBC1D3P6, ANKRD30A, LINC00993, PDLIM5, EEF1A1P5, RPL7, NKX3.1, The method may include the step of measuring the expression level of at least one gene selected from the group consisting of HSP90B1, EEF1A1, RPS24, RPL4, TMPRSS2, HSP90AA1, TPD52, TPT1, HNRNPA1, HNRNPH1, EEF1A1P6, P4HB, NDRG1, FASN, and B2M, or a protein encoded by the same.

[0081] The method of the present invention is ATP4A, PTH2, C1QL4, DSCR8, LINC02954, EIF4A1P9, CASC23, HES3, HTR3D, ATP2B3, SVOP, OR5AU1, CACNG2, PSG3, LINC02403, RN7SKP186, LHX1.DT, PDLIM1P1, GALP, KRT33A, OSBPL9P5, OR5AN1, GFY, RPL17P2, MIR5089, TMEM239, OTOAP1, CALML5, OR4K1, HSPD1P4, RN7SL219P, RPL17P11, SPRYD7P1, RNU6.949P, OR2Q1P, OR4K15, KRT8P51, ANKRD26P2, ANAPC10P1, LINC01517, MIR194.2HG, OR5B15P, RN7SKP205, LACRT, DNM1P5, KRTAP3.3, LINC01651, KRT26, KRT223P, INGX, B3GNT2P1, TUBA3GP, C10orf90, RPL15P20, XRCC6P3, LHX3, PCK1, LINC00661, C1QTNF1.AS1, ZAN, PSG1, NCOA4P4, BARHL1, RTP3, GSTA11P, OR5A2, PAEP, RNA5SP86, OR51C4P, IGHVII.1.1, SHMT1P1, RACK1, RPL6, HSPA8, CSDE1, PMEPA1, HDLBP, RPS3A, RPS8, YWHAZ, RPS4X, RPL10, RPS3, ELOVL5, HNRNPK, SCD, SLC39A6, CALR, TXNIP, RPS27A, ACTG1, RPL3, RPL19, NUDT4, RPS25, LCP1, RPL24, The method may further include the step of measuring the expression level of at least one gene selected from the group consisting of IDH1, DMXL1, NPNT, RDH11, MSMB, HMGB1, LENG8, PLPP1, HMGN2P46, RPL8, H3.3B, TBX3, SERP1, KLK3, RPS9, RPS23, ENDOD1, SPARCL1, TOMM20, SEMA3C, HLA.DRA, CRISP3, ITGB1, SEC11C, TACSTD2, KRT8, PNISR, DDX3X, PEBP1, and HSPD1, or a protein encoded by the same.

[0082] The above method of the present invention may be for predicting drug responsiveness or therapeutic responsiveness in a biological sample isolated from a target individual.

[0083] In the present invention, the term "intended individual" refers to an individual that has developed cancer or has a high probability of developing cancer, and may be a mammal including humans, and may be selected from the group consisting of, for example, humans, rats, mice, guinea pigs, hamsters, rabbits, monkeys, dogs, cats, cattle, horses, pigs, sheep, and goats, and specifically may be a human, but is not limited thereto.

[0084] In the present invention, the term "human" may refer to a patient who has developed cancer or is suspected of developing cancer, and who requires or is expected to require appropriate treatment for cancer, but is not limited thereto.

[0085] In the present invention, the biological sample refers to any substance, biological body fluid, tissue, or cell obtained from or derived from an individual, including whole blood, leukocytes, peripheral blood mononuclear cells, buffy coat, plasma, serum, sputum, tears, mucus, nasal washes, nasal aspirate, breath, urine, semen, saliva, peritoneal washings, ascites, cystic fluid, meningeal fluid, amniotic fluid, glandular fluid, pancreatic fluid, lymph fluid, pleural fluid, nipple aspirate, and bronchial aspirate. It may be one or more selected from the group consisting of synovial fluid, joint aspirate, organ secretions, cell, cell extract and cerebrospinal fluid, but is not limited thereto.

[0086] In the information-providing method of the present invention, descriptions regarding information on genes or proteins encoded by them, drugs, drug responsiveness, predictions, etc., are redundant with those previously described, and in order to avoid excessive complexity of the specification, such detailed descriptions are omitted below.

[0087] In one embodiment of the present invention, if the expression level of at least one gene selected from the group consisting of WNT5A, MIR6858, LOC100130872, HMGN2P1, and ITFG2-AS1 or the protein encoded thereby, measured for a biological sample of the target individual, is higher than that of the control group, it can be predicted that the therapeutic responsiveness of the target individual to the PARP inhibitor will be good.

[0088] In another embodiment of the present invention, if the expression level of at least one gene selected from the group consisting of LIM2, GTF2IP6, LINC02022, LILRP2, MYMX, LINC02730, RN7SL391P, RNA5SP468, LINC02209, PWWP4, DDR1.DT, KRT8P38, GAPDHP55, TRPC7.AS2, LINC01923, TSIX, KRTAP4.3, ANKRD34C.AS1, SNORD115.27, RPL18AP16, CYP2AB1P, SP7, GRM8.AS1, KASH5, CCDC63, TRPM5, SERPINA12, SCGB1D4, and TBC1D3P6, or a protein encoded thereby, measured for a biological sample of the target individual, is lower than that of a control group, it can be predicted that the therapeutic responsiveness of the target individual to a PARP inhibitor will be good. there is.

[0089] In another embodiment of the present invention, ATP4A, PTH2, C1QL4, DSCR8, LINC02954, EIF4A1P9, CASC23, HES3, HTR3D, ATP2B3, SVOP, OR5AU1, CACNG2, PSG3, LINC02403, RN7SKP186, LHX1.DT, PDLIM1P1, GALP, KRT33A, OSBPL9P5, OR5AN1, GFY, RPL17P2, MIR5089, TMEM239, OTOAP1, CALML5, OR4K1, HSPD1P4, RN7SL219P, RPL17P11, SPRYD7P1, RNU6.949P, OR2Q1P, OR4K15, KRT8P51, measured for a biological sample of the target individual If the expression level of at least one gene selected from the group consisting of ANKRD26P2, ANAPC10P1, LINC01517, MIR194.2HG, OR5B15P, RN7SKP205, LACRT, DNM1P5, KRTAP3.3, LINC01651, KRT26, KRT223P, INGX, B3GNT2P1, TUBA3GP, C10orf90, RPL15P20, XRCC6P3, LHX3, PCK1, LINC00661, C1QTNF1.AS1, ZAN, PSG1, NCOA4P4, BARHL1, RTP3, GSTA11P, OR5A2, PAEP, RNA5SP86, OR51C4P, IGHVII.1.1, and SHMT1P1 is higher than that of the control group, the above-mentioned objective It can be predicted that the individual's therapeutic responsiveness to PARP inhibitors will be good.

[0090] In another embodiment of the present invention, RACK1, RPL6, HSPA8, CSDE1, PMEPA1, HDLBP, RPS3A, RPS8, YWHAZ, RPS4X, RPL10, RPS3, ELOVL5, HNRNPK, SCD, SLC39A6, CALR, TXNIP, RPS27A, ACTG1, RPL3, RPL19, NUDT4, RPS25, XBP1, RPL37A, TM9SF3, LMAN1, GOLM1, TTC3, ACSL3, APP, FOXA1, HSPA5, DDX5, SRSF6, SFPQ, IGFBP5, RPL39, RPS20, GLUD1, MTND2P28, HNRNPDL, RPS12, MTCO1P12, RPL12, COLCA1, measured for a biological sample of the target individual If the expression level of at least one gene selected from the group consisting of LCP1, RPL24, IDH1, DMXL1, NPNT, RDH11, MSMB, HMGB1, LENG8, PLPP1, HMGN2P46, RPL8, H3.3B, TBX3, SERP1, KLK3, RPS9, RPS23, ENDOD1, SPARCL1, TOMM20, SEMA3C, HLA.DRA, CRISP3, ITGB1, SEC11C, TACSTD2, KRT8, PNISR, DDX3X, PEBP1, and HSPD1, or the protein encoded by it, is lower than that of the control group, it can be predicted that the therapeutic responsiveness of the target individual to a PARP inhibitor will be good.

[0091] In the present invention, "control group" refers to a normal control group in which drug resistance has not developed, or LIM2, GTF2IP6, LINC02022, LILRP2, MYMX, LINC02730, RN7SL391P, RNA5SP468, LINC02209, PWWP4, DDR1.DT, KRT8P38, GAPDHP55, TRPC7.AS2, LINC01923, TSIX, KRTAP4.3, ANKRD34C.AS1, SNORD115.27, RPL18AP16, CYP2AB1P, SP7, GRM8.AS1, KASH5, CCDC63, TRPM5, SERPINA12, SCGB1D4, TBC1D3P6, ANKRD30A, LINC00993, PDLIM5, in drug-sensitive cells (patient-derived cells with good drug responsiveness). EEF1A1P5, RPL7, NKX3.1, HSP90B1, EEF1A1, RPS24, RPL4, TMPRSS2, HSP90AA1, TPD52, TPT1, HNRNPA1, HNRNPH1, EEF1A1P6, P4HB, NDRG1, FASN, B2M, ATP4A, PTH2, C1QL4, DSCR8, LINC02954, EIF4A1P9, CASC23, HES3, HTR3D, ATP2B3, SVOP, OR5AU1, CACNG2, PSG3, LINC02403, RN7SKP186, LHX1.DT, PDLIM1P1, GALP, KRT33A, OSBPL9P5, OR5AN1, GFY, RPL17P2, MIR5089, TMEM239, OTOAP1, CALML5, OR4K1, HSPD1P4, RN7SL219P, RPL17P11, SPRYD7P1, RNU6.949P, OR2Q1P, OR4K15, KRT8P51, ANKRD26P2, ANAPC10P1, LINC01517, MIR194.2HG, OR5B15P, RN7SKP205, LACRT, DNM1P5, KRTAP3.3, LINC01651, KRT26, KRT223P, INGX, B3GNT2P1, TUBA3GP, C10orf90, RPL15P20, XRCC6P3, LHX3, PCK1, LINC00661, C1QTNF1.AS1, ZAN, PSG1, NCOA4P4, BARHL1, RTP3, GSTA11P, OR5A2, PAEP, RNA5SP86, OR51C4P, IGHVII.1.1, SHMT1P1, RACK1, RPL6, HSPA8, CSDE1, PMEPA1, HDLBP, RPS3A, RPS8, YWHAZ, RPS4X, RPL10, RPS3, ELOVL5, HNRNPK, SCD, SLC39A6, CALR, TXNIP, RPS27A, ACTG1, RPL3, RPL19, NUDT4, RPS25, MTCO1P12, RPL12, COLCA1, LCP1, RPL24, IDH1, DMXL1, NPNT, RDH11, MSMB, HMGB1, LENG8, PLPP1, HMGN2P46, RPL8, H3.3B, TBX3, SERP1, KLK3, RPS9, RPS23, ENDOD1, SPARCL1, TOMM20, SEMA3C, HLA.DRA, CRISP3, It may be the average to median value of the expression level of at least one gene selected from the group consisting of ITGB1, SEC11C, TACSTD2, KRT8, PNISR, DDX3X, PEBP1 and HSPD1 or the protein encoded by it.The expression level of a marker gene or a protein encoded by it in a control group can be compared with the expression level of a marker gene or a protein encoded by it in a biological sample derived from a cancer patient to be analyzed, and drug responsiveness or therapeutic responsiveness can be diagnosed or predicted by determining whether there is a significant change in the expression level.

[0092]

[0093] By utilizing the present invention, therapeutic responsiveness to PARP inhibitors can be diagnosed, thereby predicting the therapeutic responsiveness of individual cancer patients to drugs. This enables personalized precision treatment, such as easily determining whether to use additional treatment methods or alternative drugs, and ultimately improves the survival rate or survival period of cancer patients.

[0094]

[0095] Figure 1 is a schematic diagram of the process of constructing an indicator to predict drug responsiveness based on patient-derived organoids and RNA-seq analysis according to one embodiment of the present invention.

[0096] FIG. 2 is a schematic diagram of an organoid culture method according to one embodiment of the present invention.

[0097] FIG. 3a is a figure showing organoid images of a non-responder group (a) and a responder group (b) of a PARP inhibitor as a result of treating an organoid with a PARP inhibitor to confirm the responsiveness of a patient-derived prostate cancer organoid to a PARP inhibitor according to one embodiment of the present invention.

[0098] Figure 4 is a graph showing the change in organoid size by olaparib treatment to confirm the responsiveness of patient-derived prostate cancer organoids to a PARP inhibitor according to one embodiment of the present invention.

[0099] Figure 5 is a graph showing the change in organoid size by treatment with Niraparib to confirm the responsiveness of patient-derived prostate cancer organoids to a PARP inhibitor according to one embodiment of the present invention.

[0100] FIGS. 6a and 6b are figures showing the results of comparing the gene expression patterns of a PARP inhibitor non-responder group and a PARP inhibitor responder group through heatmap clustering analysis according to one embodiment of the present invention.

[0101] FIG. 7 is a figure showing the results of screening genes that increase or decrease in a PARP inhibitor response group according to one embodiment of the present invention. Specifically, FIG. 7 shows the change in expression values ​​for 100 increasing genes listed in Table 1 and 100 decreasing genes listed in Table 2 of the examples described below.

[0102] FIG. 8 is a figure showing the results of verifying genes that increase or decrease in a PARP inhibitor response group according to one embodiment of the present invention. Specifically, FIG. 8 shows the verification results of 29 positive markers and 21 negative markers that showed a significant effect in predicting PARP inhibitor responsiveness among 100 positive markers and 100 negative markers listed in Tables 1 and 2 of the examples described below.

[0103]

[0104] The present invention will be described in more detail below through examples. These examples are intended solely to explain the present invention more specifically, and it will be obvious to those skilled in the art that the scope of the present invention is not limited by these examples according to the gist of the invention.

[0105]

[0106] Examples

[0107] Experimental Method 1: Preparation of Organoids Derived from Prostate Cancer Patients

[0108] For the culture of patient-derived organoids, tissue samples were collected from various parts of the prostate using a thin needle while monitoring with ultrasound. Organoids were cultured from prostate cancer tissue according to a known protocol [Nat Protoc. Feb. 2016; 11(2): 347-358]. Briefly, 2 to 3 core needle biopsy tissues were cut with scissors in a medium containing Ad-DMEM / F-12 (Advanced Dulbecco's Modified Eagle Medium / Ham's F-12, Thermo Fisher Scientific, Waltham, MA) and 2 mM Glutamax (Thermo Fisher Scientific), 10 mM HEPES (Thermo Fisher Scientific), 100 U / ml penicillin-streptomycin (Thermo Fisher Scientific), and 50 μg / ml Primosin (Thermo Fisher Scientific), and then enzymatically treated with Collagen Type II (5 mg / mL) and DNase I (0.2 mg / ml) at 37°C for 1 hour. The treated tissues were passed through a 100 μm strainer (Falcon, Corning, NY), mixed with RPMI containing 10% fetal serum and 100 U / mL penicillin-streptomycin, and centrifuged for washing. After removing the supernatant and washing with PBS, the cell pellet (designated as 0th culture) was resuspended in growth factor-reduced Matrigel (Corning, Corning, NY) and seeded into 50 μl volume dome shapes in each well of a 24-well plate. The plates were inverted and left at 37°C for 30 minutes to allow the Matrigel domes to solidify; subsequently, 500 μl of organoid culture medium (Supplementary Table) was added to the domes, and the cells were incubated at 37°C in a CO25% incubator (see Fig. 2).

[0109]

[0110] Experimental Method 2: RNA Sequencing

[0111] Total RNA was extracted from tissue samples using TRizol® Reagent (Invitrogen, Carlsbad, CA, USA), and rRNA was removed using the Lexogen RIBO COP rRNA depletion kit (Lexogen, Vienna, Austria). RNA quality was analyzed using the NanoDrop 2000 (Thermo Fisher Scientific, Waltham, MA, USA) and the Agilent 2100 Bioanalyzer (Agilent Technologies, Santa Clara, CA, USA). RNA with an OD260 / 280 value of 1.8 or higher, an OD260 / 230 value of 1.6 or higher, and an RNA integrity number (RIN) of 7.0 or higher was used to construct an RNA library using the SMARTer® Stranded RNA-Seq Kit (Clontech Laboratories, Inc., Mountain View, CA, USA). Sequencing was performed on a Hiseq 2500 System (Illumina, San Diego, CA, USA), and base calls were performed using Illumina Casava 1.8 software. Sequencing reads were trimmed against adapter sequences, masked for low complexity or low-quality sequences using the FASTX trimmer tool, and then mapped to the hg19 whole genome using TopHat. Read counts were extracted and normalized using edgeR.

[0112]

[0113] Experimental Method 3: Differentially Expressed Gene (DEG) Analysis and Discovery of Drug Responsiveness Markers

[0114] 3.1 Analysis of Drug Reactivity

[0115] The responsiveness of the prostate cancer organoids obtained in Example 1 to the drug PARP inhibitor was analyzed. After dissociating the cultured organoids with TrypLE, 2,500 cells per 10 μL were seeded in a dome shape in a 96-well plate and cultured in organoid medium containing 1 nM DHT. When the organoid size reached 100 ± 20 μm, the drugs were administered; the drugs used were the PARP inhibitors 10 μM olaparib (Selleckchem) and 5 μM niraparib (Selleckchem), and DMSO was used as a negative control. The organoids were exposed to the drugs for 18 days, and the medium was replaced every 3 days. To evaluate organoid viability, images were acquired using ImageXpress Confocal HT.ai (Molecular Devices) before drug treatment and on day 18 after treatment. To evaluate the drug responsiveness of organoids, organoid sizes were compared, and organoid sizes were measured and analyzed using ImageJ software (version 1.53k). In this case, the change in organoid size due to drug treatment was evaluated by dividing the average organoid size of each well after drug treatment by the average organoid size before drug treatment and multiplying the result by 100.

[0116] 3.2 Analysis of Differentially Expressed Genes

[0117] The dataset was analyzed by comparing the respondent group to the non-respondent group. To obtain significant DEGs between the groups, t-tests were performed between the two groups, and genes with a p-value less than 0.05 were classified using the Excel-based Differentially Expressed Gene Analysis tool (ExDEGA, Ebiogen, Seoul, South Korea). Biomarker selection criteria were based on the signal-to-noise ratio adjusted for standard deviation, and patterns appearing specifically according to drug responsiveness for each organoid were secondarily verified.

[0118]

[0119] Experimental Result 1: Results of PARP inhibitor treatment on organoids

[0120] Drug responsiveness experiments with PARP inhibitors were performed on patient-derived prostate cancer organoids obtained in Example 1 above to obtain graphs of changes in the size of each organoid, and organoid images of the PARP inhibitor non-responder group (a) and responder group (b) are shown in Fig. 3. The experiment was performed using olaparib and niraparib as PARP inhibitors.

[0121] As a result of the experiment, the organoid size of the non-responder group did not significantly decrease even when treated with PARP inhibitors compared to the untreated control group, whereas the organoid size of the responder group significantly decreased when treated with PARP inhibitors compared to the control group (see Fig. 3). In this case, a reduction in organoid size of 20% or more was determined to be effective, and the changes in organoid size due to treatment with olaparib or niraparib were graphed and shown in Figs. 4a and 4b. As with the results confirmed in the images, it was once again confirmed that the organoid size of the responder group significantly decreased upon treatment with PARP inhibitors (see Figs. 4a and 4b).

[0122]

[0123] Experimental Result 2: Discovery of PARP Inhibitor Drug Responsiveness Markers

[0124] To identify predictive markers for drug responsiveness, the gene expression patterns of PARP inhibitor non-responders and responders classified by organoid analysis were compared using heatmap clustering.

[0125] Experimental results confirmed that the patient group responding to PARP inhibitors and the patient group not responding to them exhibited distinctly different gene expression patterns (see Figures 6a and 6b). Among these, screening of genes that increased or decreased in the PARP inhibitor responding group revealed that, as shown in Figure 7, 100 genes were statistically significantly increased in the responding patient group compared to the patient group not responding to PARP inhibitors (see Table 1), and 100 genes were statistically significantly decreased in the responding patient group compared to the patient group not responding to PARP inhibitors (see Table 2).

[0126] GeneIDbaseMeanlog2FClfcSEstatpvaluepadj1LIM2102446.333320.691560341.05255982619.658322344.91E-862.19E-842GTF2IP613588.1663818.354158991.01899864518.011956241.57E-724.98E-713LINC0202212513.6866618.235311831.02686204817.758287861.49E-704.41E-694LILRP212361.3684318.217646441.07735597416.909588743.82E-649.08E-635MYMX12157.6394917.61658120.93168873118.908226139.76E-803.76E-786LINC027307599.16794417.515711721.66527537610.518207367.12E-263.53E-257RN7SL391P4702.23746216.823139140.96967377117.349277292.00E-675.35E-668RNA5SP4684348.78825616.710403811.00774187216.582027889.40E-622.05E-609LINC022094255.41722216.679208330.94481706217.653373329.59E-702.77E-6810PWWP43973.97585516.580373311.01154547616.39112992.21E-604.65E-5911DDR1.DT3690.92045216.473798620.94449103117.441985243.96E-681.09E-6612KRT8P383159.76863516.249767731.11440931114.581507513.68E-485.15E-4713GAPDHP553044.34842216.195899760.94479204317.14229067.18E-661.81E-6414TRPC7.AS22624.38956415.981987741.19213031813.406242175.56E-415.83E-4015LINC019232534.45387415.93141170.96648434816.483879684.79E-611.03E-5916TSIX3319.01783915.74373810.93292658216.875645316.80E-641.60E-6217KRTAP4.31954.43835615.55641430.96990745216.03907086.82E-581.32E-5618ANKRD34C.AS11936.0887715.54334630.93562882116.612727135.64E-621.24E-6019SNORD115.271925.15061715.534628410.94184003216.493913924.06E-618.77E-6020RPL18AP161822.58790715.455605160.94472436416.359909563.70E-607.69E-5921CYP2AB1P1816.27776315.450738170.93080388816.599348557.05E-621.54E-6022SP73929.98800615.410097010.98043943215.717541051.15E-552.08E-5423GRM8.AS11729.17289815.379620960.9583126216.048647015.84E-581.13E-5624KASH51672.02869815.331192330.94485226416.226020633.30E-596.63E-5825CCDC631507.29165915.181617360.92957527316.331778395.86E-601.20E-5826TRPM512150.8742715.073252320.55110052227.3511851.05E-1642.53E-16227SERPINA121381.23785915.055936690.94849942615.873427319.68E-571.81E-5528SCGB1D41377.63563915.05224321.030410914.608000752.50E-483.52E-4729TBC1D3P61353.04793515.025847460.9691918815.503480553.29E-545.68E-5330ATP4A4295.52147714.992115520.87570484917.120055381.05E-652.63E-6431PTH21291.06323214.958080080.94656747915.802444532.99E-565.50E-5532C1QL41887.00662814.929056990.9272885416.099688872.56E-585.01E-573 3DSCR81189.78080614.840296481.23071976312.058225541.76E-331.3 1E-3234LINC029541112.17564114.742729070.97903786415.058384993 .04E-514.77E-5035EIF4A1P91078.29370114.698537980.9264679715.8 65133451.10E-562.05E-5536CASC231073.40889514.691518660.9813871 4514.9701561.15E-501.77E-4937HES31061.21786414.675093280.99200561214.793357121.62E-492.38E-4838HTR3D3399.27834114.650511970.85083463917.218988631.91E-664.96E-6539ATP2B310997.687214.607985860.57453732125.425651781.31E-1422.00E-14040SVOP1479.59151 214.577784020.96272113715.142270668.52E-521.36E-5041OR5AU1991.258496714.576634490.95032708515.338544724.23E-537.02E-5242CACNG2902.583452814.442378180.93333691415.473917255.20E-548.95E-5343PSG3878.623038414.402568830.93083805415.472690195.30E-549.11E-5344LINC02403873.542984114.394331980.93370114515.416423181.27E-532.16E-5245RN7SKP186862.036312214.375667680.94694107315.181163944.71E-527.56E-5146LHX1.DT1284.745114.373900150.92693554715.506903573.12E-545.39E-5347PDLIM1P1854.854294214.363093021.07232751113.394315526.53E-416.83E-4048GALP851.616076714.357511280.94383395815.211903712.95E-524.77E-5149KRT33A846.605413314.349276360.94367109515.205802563.24E-525.23E-5150OSBPL9P5841.81579714.341277930.92930484415.432264269.93E-541.69E-5251OR5AN1824.284564614.311434140.93747738715.265897981.29E-522.11E-5152GFY809.63720714.284500010.95108819215.019111925.50E-518.57E-5053RPL17P2789.369131514.249042531.15078433312.382026873.27E-352.66E-3454MIR5089765.08401314.203116410.94159922815.084035742.06E-513.25E-5055TMEM239755.427289814.184616190.96068129614.765163282.46E-493.59E-4856OTOAP18198.48004614.179499530.57229162624.776702791.60E-1352.20E-13357CALML51103.38595814.154601870.9719362814.563302314.81E-486.70E-4758OR4K1720.645462614.11763181.10367151812.791515921.83E-371.64E-3659HSPD1P461218.0083314.076449590.39441559535.689383915.78E-2797.95E-27660RN7SL219P11306.3030214.076008410.67052398420.992550227.67E-984.57E-9661RPL17P11691.336388614.056526890.9436776514.895475053.53E-505.33E-4962 SPRYD7P1660.459731413.990645060.93712860114.929269092.13E-503. 24E-4963RNU6.949P641.103437613.94769341.01085052313.797978112.6 2E-433.03E-4264OR2Q1P639.350382413.94427310.94947017914.686372 897.88E-491.13E-4765OR4K15635.354185113.935764781.25639282811.0 91885011.37E-287.91E-2866KRT8P51628.078823113.919189571.2553004811.088332871.43E-288.22E-2867ANKRD26P2917.250038513.88842640.98787886314.058835476.80E-458.39E-4468ANAPC10P1578.622697913.799773550.94952780814.533301127.45E-481.03E-4669LINC01517573.327 730513.78625730.9621898714.328000861.46E-461.91E-4570MIR194.2H G6568.9556713.734343910.55839698624.596020851.39E-1331.84E-1317 1OR5B15P546.930695113.719057690.93210865214.718303134.92E-497. 11E-4872RN7SKP205541.025780813.703406650.93271229414.691997467.25E-491.04E-4773LACRT535.462380613.689770480.94994360814.41114 0164.40E-475.92E-4674DNM1P5532.572222213.679730680.95622520514. 305971652.01E-462.61E-4575KRTAP3.31179.38456513.674081810.9268 7216114.752931832.95E-494.29E-4876LINC01651520.232888713.646532 090.94594897814.426287693.54E-474.77E-4677KRT26515.079350313.632656790.95125165714.33128311.40E-461.83E-4578KRT223P498.626483 513.585956960.93887126114.47052171.86E-472.54E-4679INGX10434.3642813.549421290.66843455220.270378392.35E-911.20E-8980B3GNT2P1479.721089613.529753691.10284028512.26809891.34E-341.06E-3381TUBA3GP479.669158513.529150520.9502714714.237142695.39E-466.91E- 4582C10orf90479.424920613.528188490.943391114.339957721.23E-461.62E-4583RPL15P203578.35039313.507072360.74195772718.204638724 .74E-741.57E-7284XRCC6P3468.888690313.496572351.0044893413.436252453.71E-413.92E-4085LHX31036.79116613.487193390.93201200914. 471051081.85E-472.52E-4686PCK11501.58311113.463898490.88629988 415.191131954.05E-526.51E-5187LINC00661680.555316713.457287151.01228783813.293933452.51E-402.56E-3988C1QTNF1.AS1670.842307913.435925961.04399607612.869709256.67E-386.11E-3789ZAN 992.255870913.424064720.93330076114.383428466.58E-478.76E-4690PSG1434.500406813.386244280.98350030613.610818623.45 E-423.82E-4191NCOA4P4643.663799513.377489240.94123315814.212726287.64E-469.72E-4592BARHL1639.015758513.365695490.9 4882131814.086630684.59E-455.70E-4493RTP31389.84796813.356462671.31196129310.18053105NANA94GSTA11P419.819314813.33 6837541.18183038711.284899841.56E-299.47E-2995OR5A2417.329547513.329217230.93565938114.245800884.76E-466.12E-4596PAEP411.960514113.309630280.92922644314.32334431.56E-462.05E-4597RNA5SP86407.32845113.292973981.08166101712.2894083 91.03E-348.22E-3498OR51C4P2591.75188713.253623871.19563508811.085007461.48E-288.53E-2899IGHVII.1.1384.859598613.21 1304581.03401873912.776658762.21E-371.98E-36100SHMT1P1376.829062513.180266840.94181171413.994587921.68E-442.04E-43.

[0127]

[0128] GeneIDbaseMeanlog2FoldChangelfcSEstatpvaluepadj1ANKRD30A675.931658-25.303449073.225951594-7.8437162914.37E-151.18E-142LINC00993169.785263-23.879423663.226030152-7.4021080221.34E-133.36E-133PDLIM517531.51363-16.177871371.094588317-14.779868491.98E-492.90E-484EEF1A1P516221.08458-16.065788011.075160329-14.942690471.74E-502.66E-495RPL714319.41549-15.885886341.195250346-13.290844382.62E-402.67E-396NKX3.112735.82684-15.716812411.04051299-15.1048691.50E-512.38E-507HSP90B112667.73637-15.709076431.061236015-14.80262281.41E-492.08E-488EEF1A175100.83345-15.550899860.735263628-21.150100822.75E-991.72E-979RPS2410635.60474-15.456820311.054005997-14.664831471.08E-481.55E-4710RPL410519.41721-15.440971741.058234417-14.591258323.19E-484.48E-4711TMPRSS210363.28892-15.419406751.066441822-14.458741612.21E-473.00E-4612HSP90AA19798.164614-15.338508741.052839404-14.568706954.44E-486.20E-4713TPD528471.533931-15.128608661.223682547-12.363180874.13E-353.35E-3414TPT18426.94557-15.121002121.060973527-14.252006994.36E-465.62E-4515HNRNPA18340.30736-15.1060871.043988073-14.469597291.89E-472.57E-4616HNRNPH18153.958735-15.073488921.049200294-14.366645728.38E-471.11E-4517EEF1A1P68110.210535-15.065726871.075894529-14.002977481.49E-441.82E-4318P4HB8076.892548-15.059790031.043162957-14.436661053.04E-474.11E-4619NDRG18042.346612-15.053612271.045784068-14.394570285.60E-477.48E-4620FASN8027.669963-15.050966441.283989252-11.72203469.83E-326.76E-3121B2M21347.51967-15.023877451.10702432-13.571406865.92E-426.48E-4122RACK17667.480552-14.984738021.099948725-13.623124132.92E-423.24E-4123RPL67535.604838-14.959710991.086617162-13.767232394.01E-434.61E-4224HSPA812141.22102-14.926459921.055821667-14.137292672.24E-452.82E-4425CSDE17207.730251-14.895540861.037379908-14.358809879.38E-471.24E-4526PMEPA17193.600158-14.892705931.073059813-13.878728618.52E-441.00E-4227HDLBP7095.05381-14.872810921.033003268-14.39764175.35E-477.17E-4628RPS3A7017.885689-14.857021781.062028991-13.989280811.81E-442.20E-4329RPS86887.051636-14.829872711.069104008-13.871309629.45E-441.11E-4230YWHAZ6759.118 549-14.802835331.045746898-14.155275391.73E-452.19E-4431RPS4X6 708.641207-14.792005491.049123938-14.099388033.83E-454.77E-4432RPL106666.104041-14.782829861.057812863-13.974900832.22E-442.6 7E-4333RPS36328.458144-14.707841511.084755654-13.558667767.04E -427.65E-4134ELOVL56215.791082-14.681926851.118577102-13.125538 532.35E-392.31E-3835HNRNPK5991.401871-14.628879351.032986997-1 4.161726531.58E-452.00E-4436SCD5953.924499-14.619829911.2372590 57-11.816304623.22E-322.26E-3137SLC39A65942.802609-14.617132781.046258398-13.970863032.35E-442.82E-4338CALR5811.923376-14.585004141.047012763-13.930111124.16E-444.95E-4339TXNIP5658.771249-14.546475881.11809252-13.010082461.07E-381.02E-3740RPS27A5654 .242481-14.545317181.053916612-13.801203072.51E-432.90E-4241AC TG15627.054814-14.538362871.048817596-13.861669481.08E-431.27E- 4242RPL314732.35932-14.493113821.030128131-14.069234095.87E-457.25E-4443RPL195312.240981-14.455304781.056299816-13.684850241.25E-421.41E-4144NUDT44934.149574-14.348794051.146933183-12.510575386.53E-365.50E-3545RPS254814.766086-14.313448271.054008697-13.580009645.26E-425.76E-4146XBP14778.979537-14.302687341.027349051-13.921935614.66E-445.55E-4347RPL37A4665.042489-14.26787321.069117387-13.345469241.26E-401.30E-3948TM9SF37493.979834-14.230310841.038732649-13.699685731.02E-421.15E-4149LMAN14477.51747-14.208682471.047724962-13.56146226.78E-427.39E-4150GOLM17321.311669-14.196701061.081404133-13.128025532.28E-392.24E-3851TTC34433.941349-14.194594991.027564036-13.813830082.10E-432.44E-4252ACSL34371.678193-14.174180141.09943762-12.892209514.98E-384.60E-3753APP4335.19233-14.162090691.09196803-12.969327221.83E-381.72E-3754FOXA14200.248607-14.116466361.053708756-13.396933726.30E-416.60E-4055HSPA56915.851695-14.114477611.061089106-13.301877792.26E-402.31E-3956DDX511356.15381-14.113907031.007200821-14.013001921.30E-441.59E-4357SRSF64166.898472-14.104961811.052721533-13.398568726.16E-416.46E-4058SFPQ4156.709239-14.101438581.040086385-13.55794947.11E-427.73E-4159IGFBP54143.427292-14.096826151.090119516-12.931450122.99E-382.79E-3760RPL394139.833189-14.09555431.06780454-13.200500438.72E-408.71E-3961RPS204054.987975-14.06567811.039043605-13.537139389.44E-421.02E-4062GLUD14042.372988-14.061202761.060587609-13.25793614.06E-404.11E-3963MTND2P2815603.74921-13.995746520.918546356-15.236842892.01E-523.27E-5164HNRNPDL3851.640113-13.991470461.039840334-13.455402722.86E-413.04E-4065RPS123834.150203-13.984890551.097894792-12.737915013.64E-373.22E-3666MTCO1P1230336.17464-13.974357330.664868369-21.018231544.47E-982.68E-9667RPL126133.671773-13.941331841.070781236-13.0197769.44E-399.04E-3868COLCA13705.375416-13.935613141.063719482-13.100834733.26E-393.18E-3869LCP13671.100452-13.922211031.071169471-12.997206711.27E-381.20E-3770RPL243598.060825-13.893198021.108457229-12.533815164.88E-364.12E-3571IDH13558.287654-13.877182061.116804147-12.42579741.89E-351.56E-3472DMXL13553.646033-13.875290521.118324241-12.407216092.39E-351.96E-3473NPNT3519.648703-13.861431391.064769563-13.018245329.64E-399.21E-3874RDH119526.453226-13.855924821.05026059-13.192844679.65E-409.63E-3975MSMB5759.033986-13.850384761.263551378-10.961473365.85E-283.26E-2776HMGB13485.591765-13.847404681 .034306738-13.388102567.10E-417.42E-4077LENG83446.072109-13.83 0928431.034422224-13.370679888.97E-419.35E-4078PLPP13409.20584 -13.815416411.14231304-12.094247311.13E-338.54E-3379HMGN2P4632 76.63321-13.758196331.165017537-11.809432823.49E-322.45E-3180RP L85346.134762-13.74307191.065062835-12.903531564.30E-383.99E-3781H3.3B3160.280175-13.706046231.056485733-12.973243091.74E-38 1.64E-3782TBX33100.149287-13.678338451.081995802-12.641766651.24E-361.07E-3583SERP15087.756761-13.671597191.048505394-13.0391 2917.33E-397.05E-3884KLK3118308.5219-13.665367350.432409601-31.602830553.38E-2191.73E-21685RPS92978.252331-13.620441751.061000378-12.837358061.01E-379.20E-3786RPS232972.501406-13.617651411.067587988-12.755530752.90E-372.58E-3687ENDOD12920.340403-13.592130361.121285458-12.121917998.08E-346.15E-3388SPARCL12904.044266-13.584066931.054279034-12.884697975.49E-385.05E-37 89TOMM202867.737174-13.565892761.043225151-13.003801481.16E-381.11E-3790SEMA3C2865.42482-13.564744451.151617317-11.7788 6465.02E-323.50E-3191HLA.DRA2854.595885-13.559271831.197137572-11.326410739.71E-305.99E-2992CRISP34682.616225-13.551783272.22656382-6.0864113351.15E-092.41E-0993ITGB14682.015265-13.551707551.041579442-13.010728721.06E-381.01E-3794SEC11C2 838.316553-13.551013821.12009923-12.098047621.08E-338.17E-3395TACSTD22818.803697-13.541072341.04953494-12.901973844.39E-384.07E-3796KRT82810.081672-13.536611781.069130568-12.661327059.68E-378.43E-3697PNISR2796.912687-13.52981861.06824136 3-12.665507149.18E-378.00E-3698DDX3X2790.174251-13.526346061.032859918-13.096012183.47E-393.38E-3899PEBP12787.518914-13.524964481.063153891-12.721549154.49E-373.95E-36100HSPD14541.669684-13.50775451.047294138-12.897765784.63E-384.29E-37.

[0129]

[0130] Experimental Result 3: Verification of the Predictive Effect of PARP Inhibitors on Drug Responsiveness

[0131] To verify the drug responsiveness prediction effects of the 100 positive markers and 100 negative markers mentioned above, the inventors obtained samples from a patient group showing responsiveness to PARP inhibitors and compared their expression levels.

[0132] As shown in Tables 1 and 2 below, among the 100 positive marker and 100 negative marker genes, a total of 29 positive markers including LIM2, GTF2IP6, LINC02022, LILRP2, MYMX, LINC02730, RN7SL391P, RNA5SP468, LINC02209, PWWP4, DDR1.DT, KRT8P38, GAPDHP55, TRPC7.AS2, LINC01923, TSIX, KRTAP4.3, ANKRD34C.AS1, SNORD115.27, RPL18AP16, CYP2AB1P, SP7, GRM8.AS1, KASH5, CCDC63, TRPM5, SERPINA12, SCGB1D4, and TBC1D3P6, and ANKRD30A, LINC00993, PDLIM5, The effects of a total of 21 voice markers, including EEF1A1P5, RPL7, NKX3.1, HSP90B1, EEF1A1, RPS24, RPL4, TMPRSS2, HSP90AA1, TPD52, TPT1, HNRNPA1, HNRNPH1, EEF1A1P6, P4HB, NDRG1, FASN, and B2M, could be verified (see Fig. 8).

[0133] As a result of investigating the drug responsiveness of DEG markers identified through screening in patients responsive to PARP inhibitors, it was confirmed that patients with and without resistance could be statistically distinguished. Accordingly, by identifying gene combinations capable of predicting individual drug responsiveness to PARP inhibitors, the present invention is expected to be utilized in a personalized treatment prediction system.

[0134]

[0135] Experimental Result 4: Confirmation of PARP Inhibitor Non-Responder Specific Signature

[0136] The inventors further examined whether the above negative markers could be utilized as signatures specific to the PARP inhibitor non-responder group. As confirmed in Experimental Result 2, 100 genes were statistically significantly reduced in the responding patient group compared to the non-responding patient group, and these genes correspond to a group of genes that show relatively high expression in the non-responding patient group. Therefore, the above 100 negative markers can be interpreted as signatures specific to the non-responder group that reflect expression patterns specific to the PARP inhibitor non-responder group.

[0137] In addition, as confirmed in Experimental Results 3, a total of 21 genes among 100 negative markers—ANKRD30A, LINC00993, PDLIM5, EEF1A1P5, RPL7, NKX3.1, HSP90B1, EEF1A1, RPS24, RPL4, TMPRSS2, HSP90AA1, TPD52, TPT1, HNRNPA1, HNRNPH1, EEF1A1P6, P4HB, NDRG1, FASN, and B2M—showed a predictive effect that could significantly distinguish between patients resistant to PARP inhibitors and those not resistant.

[0138] Therefore, the negative marker of the present invention is not merely limited to a gene group that is reduced in the responder group, but can be usefully utilized as a non-responder-specific signature that reflects gene expression patterns commonly observed in the PARP inhibitor non-responder group. Furthermore, the non-responder-specific signature can be utilized as a signature for predicting drug responsiveness in conjunction with a positive marker, and can also be usefully utilized alone to predict low responsiveness or resistance to PARP inhibitors.

[0139]

[0140] Foregoing, specific parts of the present invention have been described in detail. It is evident to those skilled in the art that such specific descriptions are merely preferred embodiments and do not limit the scope of the invention. Accordingly, the actual scope of the invention is defined by the appended claims and their equivalents.

Claims

1. LIM2, GTF2IP6, LINC02022, LILRP2, MYMX, LINC02730, RN7SL391P, RNA5SP468, LINC02209, PWWP4, DDR1.DT, KRT8P38, GAPDHP55, TRPC7.AS2, LINC01923, TSIX, KRTAP4.3, ANKRD34C.AS1, SNORD115.27, RPL18AP16, CYP2AB1P, SP7, GRM8.AS1, KASH5, CCDC63, TRPM5, SERPINA12, SCGB1D4, TBC1D3P6, ANKRD30A, LINC00993, PDLIM5, EEF1A1P5, RPL7, NKX3.1, HSP90B1, EEF1A1, A composition for predicting drug responsiveness comprising a preparation for measuring the expression level of at least one gene selected from the group consisting of RPS24, RPL4, TMPRSS2, HSP90AA1, TPD52, TPT1, HNRNPA1, HNRNPH1, EEF1A1P6, P4HB, NDRG1, FASN, and B2M, or a protein encoded by it.

2. In Paragraph 1, 상기 조성물은 ATP4A, PTH2, C1QL4, DSCR8, LINC02954, EIF4A1P9, CASC23, HES3, HTR3D, ATP2B3, SVOP, OR5AU1, CACNG2, PSG3, LINC02403, RN7SKP186, LHX1.DT, PDLIM1P1, GALP, KRT33A, OSBPL9P5, OR5AN1, GFY, RPL17P2, MIR5089, TMEM239, OTOAP1, CALML5, OR4K1, HSPD1P4, RN7SL219P, RPL17P11, SPRYD7P1, RNU6.949P, OR2Q1P, OR4K15, KRT8P51, ANKRD26P2, ANAPC10P1, LINC01517, MIR194.2HG, OR5B15P, RN7SKP205, LACRT, DNM1P5, KRTAP3.3, LINC01651, KRT26, KRT223P, INGX, B3GNT2P1, TUBA3GP, C10orf90, RPL15P20,1, SHMT1P1, RACK1, RPL6, HSPA8, CSDE1, PMEPA1, HDLBP, RPS3A, RPS8, YWHAZ, RPS4X, RPL10, RPS3, ELOVL5, HNRNPK, SCD, SLC39A6, CALR, TXNIP, RPS27A, ACTG1, RPL3, RPL19, NUDT4, RPS25, LCP1, RPL24, A composition further comprising a preparation for measuring the expression level of at least one gene selected from the group consisting of IDH1, DMXL1, NPNT, RDH11, MSMB, HMGB1, LENG8, PLPP1, HMGN2P46, RPL8, H3.3B, TBX3, SERP1, KLK3, RPS9, RPS23, ENDOD1, SPARCL1, TOMM20, SEMA3C, HLA.DRA, CRISP3, ITGB1, SEC11C, TACSTD2, KRT8, PNISR, DDX3X, PEBP1, and HSPD1 genes, or a protein encoded by such gene.

3. In Paragraph 1, A composition comprising a preparation for measuring the expression level of the above gene, wherein the preparation is a primer that specifically binds to a nucleic acid molecule of the above gene or a probe that specifically binds to a nucleic acid molecule of the above gene.

4. In Paragraph 1, A composition comprising one or more selected from the group consisting of an antibody that specifically binds to the protein, or an antigen-binding fragment thereof; an oligopeptide; a ligand; PNA (peptide nucleic acid); and an aptamer.

5. In Paragraph 1, The above-mentioned drug is a composition that is a drug for treating cancer.

6. In Paragraph 5, A composition wherein the above cancer is one or more selected from the group consisting of prostate cancer, colorectal cancer, breast cancer, mammary gland cancer, glioma, thyroid cancer, parathyroid cancer, lung cancer, liver cancer, pancreatic cancer, head and neck cancer, stomach cancer, urothelial carcinoma, kidney cancer, testicular cancer, penile cancer, cervical cancer, ovarian cancer, endometrial cancer, fallopian tube cancer, uterine cancer, vaginal cancer, melanoma, skin cancer, blood cancer, bone cancer, brain cancer, endocrine cancer, ureteral cancer, urethral cancer, bronchial cancer, bladder cancer, bone marrow cancer, leukemia, cervical cancer, intestinal cancer, esophageal cancer, sarcoma, tongue cancer, lymphoma, and neuroblastoma.

7. In Paragraph 5, A composition characterized in that the above drug is a PARP (Poly ADP-Ribose Polymerase) inhibitor.

8. In Paragraph 7, The above PARP inhibitor is a composition comprising: a nucleic acid molecule that inhibits the expression of the PARP1, PARP2, or PARP3 gene; an antibody, its antigen-binding fragment, or aptamer that specifically binds to the protein encoded by the gene; or a small molecule compound, peptide, or natural product that inhibits the activity of PARP1, PARP2, or PARP3.

9. In Paragraph 7, A composition wherein the above-mentioned PARP inhibitor is at least one selected from the group consisting of olaparib, niraparib, rucaparib, talazoparib, and veliparib.

10. A kit for predicting drug responsiveness comprising a composition of any one of claims 1 to 9.

11. In Paragraph 10, The above kit is a kit selected from the group consisting of RT-PCR kits, DNA chip kits, ELISA kits, protein chip kits, rapid kits, and MRM (Multiple reaction monitoring) kits.

12. With respect to biological samples isolated from the target individual, LIM2, GTF2IP6, LINC02022, LILRP2, MYMX, LINC02730, RN7SL391P, RNA5SP468, LINC02209, PWWP4, DDR1.DT, KRT8P38, GAPDHP55, TRPC7.AS2, LINC01923, TSIX, KRTAP4.3, ANKRD34C.AS1, SNORD115.27, RPL18AP16, CYP2AB1P, SP7, GRM8.AS1, KASH5, CCDC63, TRPM5, SERPINA12, SCGB1D4, TBC1D3P6, ANKRD30A, LINC00993, PDLIM5, EEF1A1P5, RPL7, NKX3.1, HSP90B1, EEF1A1, RPS24, A method for providing information for predicting drug responsiveness, comprising the step of measuring the expression level of at least one gene selected from the group consisting of RPL4, TMPRSS2, HSP90AA1, TPD52, TPT1, HNRNPA1, HNRNPH1, EEF1A1P6, P4HB, NDRG1, FASN, and B2M, or a protein encoded by it.

13. In Paragraph 12, Read ATP4A, PTH2, C1QL4, DSCR8, LINC02954, EIF4A1P9, CASC23, HES3, HTR3D, ATP2B3, SVOP, OR5AU1, CACNG2, PSG3, LINC02403, RN7SKP186, LHX1.DT, PDLIM1P1, GALP, KRT33A, OSBPL9P5, OR5AN1, GFY, RPL17P2, MIR5089, TMEM239, OTOAP1, CALML5, OR4K1, HSPD1P4, RN7SL219P, RPL17P11, SPRYD7P1, RNU6.949P, OR2Q1P, OR4K15, KRT8P51, ANKRD26P2, ANAPC10P1, LINC01517, MIR194.2HG, OR5B15P, RN7SKP205, LACRT, DNM1P5, KRTAP3.3, LINC01651, KRT26, KRT223P, INGX, B3GNT2P1, TUBA3GP, C10orf90, RPL15P20,1, SHMT1P1, RACK1, RPL6, HSPA8, CSDE1, PMEPA1, HDLBP, RPS3A, RPS8, YWHAZ, RPS4X, RPL10, RPS3, ELOVL5, HNRNPK, SCD, SLC39A6, CALR, TXNIP, RPS27A, ACTG1, RPL3, RPL19, NUDT4, RPS25, LCP1, RPL24, A method further comprising the step of measuring the expression level of at least one gene selected from the group consisting of IDH1, DMXL1, NPNT, RDH11, MSMB, HMGB1, LENG8, PLPP1, HMGN2P46, RPL8, H3.3B, TBX3, SERP1, KLK3, RPS9, RPS23, ENDOD1, SPARCL1, TOMM20, SEMA3C, HLA.DRA, CRISP3, ITGB1, SEC11C, TACSTD2, KRT8, PNISR, DDX3X, PEBP1, and HSPD1 genes, or a protein encoded by such gene.

14. In Paragraph 12, The above drug is a PARP (Poly ADP-Ribose Polymerase) inhibitor, method.

15. In Paragraph 12, A method for predicting that the therapeutic responsiveness of the target individual to a PARP inhibitor will be good when the expression level of at least one gene selected from the group consisting of LIM2, GTF2IP6, LINC02022, LILRP2, MYMX, LINC02730, RN7SL391P, RNA5SP468, LINC02209, PWWP4, DDR1.DT, KRT8P38, GAPDHP55, TRPC7.AS2, LINC01923, TSIX, KRTAP4.3, ANKRD34C.AS1, SNORD115.27, RPL18AP16, CYP2AB1P, SP7, GRM8.AS1, KASH5, CCDC63, TRPM5, SERPINA12, SCGB1D4, and TBC1D3P6 measured in the biological sample is higher than that of a control group.

16. In Paragraph 12, A method for predicting that the therapeutic responsiveness of the target individual to a PARP inhibitor will be good when the expression level of at least one gene selected from the group consisting of ANKRD30A, LINC00993, PDLIM5, EEF1A1P5, RPL7, NKX3.1, HSP90B1, EEF1A1, RPS24, RPL4, TMPRSS2, HSP90AA1, TPD52, TPT1, HNRNPA1, HNRNPH1, EEF1A1P6, P4HB, NDRG1, FASN, and B2M, measured in the biological sample above, is lower than that of the control group.

17. In Paragraph 13, ATP4A, PTH2, C1QL4, DSCR8, LINC02954, EIF4A1P9, CASC23, HES3, HTR3D, ATP2B3, SVOP, OR5AU1, CACNG2, PSG3, LINC02403, RN7SKP186, LHX1.DT, PDLIM1P1, GALP, KRT33A, OSBPL9P5, OR5AN1, GFY, RPL17P2, MIR5089, TMEM239, OTOAP1, CALML5, OR4K1, HSPD1P4, RN7SL219P, RPL17P11, SPRYD7P1, RNU6.949P, OR2Q1P, OR4K15, KRT8P51, ANKRD26P2, measured in the above biological samples If the expression level of at least one gene selected from the group consisting of ANAPC10P1, LINC01517, MIR194.2HG, OR5B15P, RN7SKP205, LACRT, DNM1P5, KRTAP3.3, LINC01651, KRT26, KRT223P, INGX, B3GNT2P1, TUBA3GP, C10orf90, RPL15P20, XRCC6P3, LHX3, PCK1, LINC00661, C1QTNF1.AS1, ZAN, PSG1, NCOA4P4, BARHL1, RTP3, GSTA11P, OR5A2, PAEP, RNA5SP86, OR51C4P, IGHVII.1.1, and SHMT1P1 is higher than that of the control group, treatment with a PARP inhibitor of the target individual A method that predicts good reactivity.

18. In Paragraph 13, RACK1, RPL6, HSPA8, CSDE1, PMEPA1, HDLBP, RPS3A, RPS8, YWHAZ, RPS4X, RPL10, RPS3, ELOVL5, HNRNPK, SCD, SLC39A6, CALR, TXNIP, RPS27A, ACTG1, RPL3, RPL19, NUDT4, RPS25, XBP1, RPL37A, TM9SF3, LMAN1, GOLM1, TTC3, ACSL3, APP, FOXA1, HSPA5, DDX5, SRSF6, SFPQ, IGFBP5, RPL39, RPS20, GLUD1, MTND2P28, HNRNPDL, RPS12, MTCO1P12, RPL12, COLCA1, LCP1, RPL24, IDH1, measured in the above biological samples A method for predicting that the therapeutic responsiveness of the target individual to a PARP inhibitor will be good when the expression level of at least one gene selected from the group consisting of DMXL1, NPNT, RDH11, MSMB, HMGB1, LENG8, PLPP1, HMGN2P46, RPL8, H3.3B, TBX3, SERP1, KLK3, RPS9, RPS23, ENDOD1, SPARCL1, TOMM20, SEMA3C, HLA.DRA, CRISP3, ITGB1, SEC11C, TACSTD2, KRT8, PNISR, DDX3X, PEBP1, and HSPD1, or the protein encoded thereby, is lower than that of the control group.

19. A device for predicting drug responsiveness comprising a composition of any one of claims 1 to 9.

20. In Paragraph 12, A method for predicting that the therapeutic responsiveness of the target individual to a PARP inhibitor is low when the expression level of at least one gene selected from the group consisting of LIM2, GTF2IP6, LINC02022, LILRP2, MYMX, LINC02730, RN7SL391P, RNA5SP468, LINC02209, PWWP4, DDR1.DT, KRT8P38, GAPDHP55, TRPC7.AS2, LINC01923, TSIX, KRTAP4.3, ANKRD34C.AS1, SNORD115.27, RPL18AP16, CYP2AB1P, SP7, GRM8.AS1, KASH5, CCDC63, TRPM5, SERPINA12, SCGB1D4, and TBC1D3P6, measured in the biological sample above, is lower than that of a control group.

21. In Paragraph 12, A method for predicting that the therapeutic responsiveness of the target individual to a PARP inhibitor will be low when the expression level of at least one gene selected from the group consisting of ANKRD30A, LINC00993, PDLIM5, EEF1A1P5, RPL7, NKX3.1, HSP90B1, EEF1A1, RPS24, RPL4, TMPRSS2, HSP90AA1, TPD52, TPT1, HNRNPA1, HNRNPH1, EEF1A1P6, P4HB, NDRG1, FASN, and B2M, measured in the biological sample above, is higher than that of a control group.

22. In Paragraph 13, ATP4A, PTH2, C1QL4, DSCR8, LINC02954, EIF4A1P9, CASC23, HES3, HTR3D, ATP2B3, SVOP, OR5AU1, CACNG2, PSG3, LINC02403, RN7SKP186, LHX1.DT, PDLIM1P1, GALP, KRT33A, OSBPL9P5, OR5AN1, GFY, RPL17P2, MIR5089, TMEM239, OTOAP1, CALML5, OR4K1, HSPD1P4, RN7SL219P, RPL17P11, SPRYD7P1, RNU6.949P, OR2Q1P, OR4K15, KRT8P51, ANKRD26P2, measured in the above biological samples Treatment of the target individual with a PARP inhibitor when the expression level of at least one gene selected from the group consisting of ANAPC10P1, LINC01517, MIR194.2HG, OR5B15P, RN7SKP205, LACRT, DNM1P5, KRTAP3.3, LINC01651, KRT26, KRT223P, INGX, B3GNT2P1, TUBA3GP, C10orf90, RPL15P20, XRCC6P3, LHX3, PCK1, LINC00661, C1QTNF1.AS1, ZAN, PSG1, NCOA4P4, BARHL1, RTP3, GSTA11P, OR5A2, PAEP, RNA5SP86, OR51C4P, IGHVII.1.1, and SHMT1P1 is lower than that of the control group A method that predicts low reactivity.

23. In Paragraph 13, RACK1, RPL6, HSPA8, CSDE1, PMEPA1, HDLBP, RPS3A, RPS8, YWHAZ, RPS4X, RPL10, RPS3, ELOVL5, HNRNPK, SCD, SLC39A6, CALR, TXNIP, RPS27A, ACTG1, RPL3, RPL19, NUDT4, RPS25, XBP1, RPL37A, TM9SF3, LMAN1, GOLM1, TTC3, ACSL3, APP, FOXA1, HSPA5, DDX5, SRSF6, SFPQ, IGFBP5, RPL39, RPS20, GLUD1, MTND2P28, HNRNPDL, RPS12, MTCO1P12, RPL12, COLCA1, LCP1, RPL24, IDH1, measured in the above biological samples A method for predicting that the therapeutic responsiveness of the target individual to a PARP inhibitor will be low when the expression level of at least one gene selected from the group consisting of DMXL1, NPNT, RDH11, MSMB, HMGB1, LENG8, PLPP1, HMGN2P46, RPL8, H3.3B, TBX3, SERP1, KLK3, RPS9, RPS23, ENDOD1, SPARCL1, TOMM20, SEMA3C, HLA.DRA, CRISP3, ITGB1, SEC11C, TACSTD2, KRT8, PNISR, DDX3X, PEBP1, and HSPD1, or the protein encoded thereby, is higher than that of the control group.