Personalized cancer treatment method for cancer patients

Abstract

The present invention relates to a cancer patient-specific cancer treatment method. Specifically, changes in expression of 87 target genes according to the present invention and mutations of some of the genes are quantified using a quantitative real-time PCR method and the quantitative results are analyzed, whereby gene expression patterns for individual cancer patients can be accurately and conveniently profiled. Therefore, the method for analyzing the expression patterns of target genes in cancer patients according to the present invention can provide information on existing cancer therapeutics or future cancer treatment drugs that could be selectively administered to cancer patients, thereby finding applications in personalized treatments for individual patients.

Description

Customized cancer treatment methods for cancer patients

[0001] The present invention relates to a method for personalized cancer treatment for cancer patients, and more particularly, to a method for personalized drug selection for cancer patients and a kit used therefor.

[0002] Cancer is a disease that threatens human health and life, accounting for approximately 13% of all deaths. In 2007, 7.6 million people worldwide died from cancer. In the United States, 1.4 million new cases of cancer have been reported each year over the past several years, making cancer the second leading cause of death. According to statistics from the SEER report, the mortality rate for all cancer types in the United States increased from 195.4 per 100,000 people in 1950 to 204.4 per 100,000 people in 1978, and then steadily decreased to 184.0 per 100,000 people in 2005. This decline is likely due to earlier detection of cancer due to improved diagnostic techniques. Early detection and treatment play a crucial role in prognosis and survival for all cancer types.

[0003] There are approximately 300 cancer treatments approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) and already in clinical use. These treatments are approved for at least one type of cancer and target specific targets.

[0004] Conventional cancer chemotherapy involves selecting and administering appropriate anticancer drugs based on the type and severity of the cancer, rather than the individual patient. However, clinical results generally show that the therapeutic effects of this type of chemotherapy vary significantly from patient to patient, and various methods have been proposed to overcome this limitation.

[0005] Accordingly, the present inventors have endeavored to develop a method for easily and accurately selecting a drug suitable for each cancer patient. As a result, they have quantified and analyzed the expression changes of 87 genes and mutations of some of these genes as targets of cancer treatments approved by the U.S. FDA using a quantitative real-time PCR method (qPCR), thereby revealing that the expression patterns of each cancer patient can be conveniently profiled with high accuracy and thus a customized drug can be selected for each cancer patient, leading to the present application.

[0006] [Prior Art Literature]

[0007] [Patent Document]

[0008] Republic of Korea Patent No. 10-1371697

[0009] The purpose of the present invention is to provide a kit for screening personalized medicine for cancer patients using cancer treatment targets and a use thereof, as a method for more efficiently administering chemotherapy to cancer patients.

[0010] In order to achieve the purpose of the present invention, the present invention provides a method for treating ACPP, ADA, ALK, BCR-ABL-1, BTK, CDK4, CDK6, CD19, CD3D, CD52, C-MET, CRBN, CTLA4, CYP17A1, DDR2, ERBB4, FCGR1A, FGF1, FGFR1, FGFR2, FGFR3, FRK, GNRH1, GNRHR, HDAC2, HDAC3, HPRT1, IFNAR1, IFNAR2, IL2RA, IL2RB, IL2RG, ITK, JAK1, JAK2, LDLR, LHCGR, LIMK1, MAP1A, MAP2, MAP2K1, MAP2K2, MAPK11, NEK11, NR3C1, NTRK1, PARP1, PARP2, PARP3, PDCD1, PGF, PIK3CD, A kit for screening cancer patients with personalized medicine is provided, comprising primers or probes that specifically hybridize to at least two target genes each selected from the group consisting of PRLR, PSMB10, PSMB1, PSMB2, PSMB8, PSMB9, PSMD1, PSMD2, PTK6, RARA, RARB, RARG, RPL3, SH2B3, SIK1, SLC2A2, SMO, SSTR2, SSTR5, TEK, TLR8, TNFSF8, TNFSF11, TOP1MT, TOP2B, TUBA1A, TUBA4A, TUBB1, TUBB3, TUBB, TUBD1, TUBE1, TUBG1, VEGFA, and VEGFB.

[0011] In addition, the present invention

[0012] 1) ACPP, ADA, ALK, BCR-ABL-1, BTK, CDK4, CDK6, CD19, CD3D, CD52, C-MET, CRBN, CTLA4, CYP17A1, DDR2, ERBB4, FCGR1A, FGF1, FGFR1, FGFR2, FGFR3, FRK, GNRH1, GNRHR, HDAC2, HDAC3, HPRT1, IFNAR1, IFNAR2, IL2RA, IL2RB, IL2RG, ITK, JAK1, JAK2, LDLR, LHCGR, LIMK1, MAP1A, MAP2, MAP2K1, MAP2K2, MAPK11, NEK11, NR3C1, NTRK1, PARP1, PARP2, PARP3, PDCD1, PGF, PIK3CD, A step of measuring the expression of at least two target genes selected from the group consisting of PRLR, PSMB10, PSMB1, PSMB2, PSMB8, PSMB9, PSMD1, PSMD2, PTK6, RARA, RARB, RARG, RPL3, SH2B3, SIK1, SLC2A2, SMO, SSTR2, SSTR5, TEK, TLR8, TNFSF8, TNFSF11, TOP1MT, TOP2B, TUBA1A, TUBA4A, TUBB1, TUBB3, TUBB, TUBD1, TUBE1, TUBG1, VEGFA and VEGFB; and

[0013] 2) A method for screening a drug tailored to a cancer patient is provided, including a step of screening a drug that acts on a target gene measured to be highly expressed in step 1).

[0014] In addition, the present invention

[0015] 1) A step of isolating and proliferating cancer cells and normal cells from cancer tissue and normal tissue isolated from a cancer patient;

[0016] 2) A step of treating the cancer cells of step 1) with a cancer treatment candidate drug;

[0017] 3) A step of isolating total RNA from the cancer cells and normal cells of step 1) and the cancer cells treated with the cancer treatment candidate drug of step 2), and synthesizing cDNA using the total RNA as a template;

[0018] 4) Using the cDNA synthesized in the above step 3) as a template, ACPP, ADA, ALK, BCR-ABL-1, BTK, CDK4, CDK6, CD19, CD3D, CD52, C-MET, CRBN, CTLA4, CYP17A1, DDR2, ERBB4, FCGR1A, FGF1, FGFR1, FGFR2, FGFR3, FRK, GNRH1, GNRHR, HDAC2, HDAC3, HPRT1, IFNAR1, IFNAR2, IL2RA, IL2RB, IL2RG, ITK, JAK1, JAK2, LDLR, LHCGR, LIMK1, MAP1A, MAP2, MAP2K1, MAP2K2, MAPK11, NEK11, NR3C1, NTRK1, PARP1, PARP2, PARP3, PDCD1, A step of amplifying a target gene using primers or probes that specifically hybridize to each of at least two target genes selected from the group consisting of PGF, PIK3CD, PRLR, PSMB10, PSMB1, PSMB2, PSMB8, PSMB9, PSMD1, PSMD2, PTK6, RARA, RARB, RARG, RPL3, SH2B3, SIK1, SLC2A2, SMO, SSTR2, SSTR5, TEK, TLR8, TNFSF8, TNFSF11, TOP1MT, TOP2B, TUBA1A, TUBA4A, TUBB1, TUBB3, TUBB, TUBD1, TUBE1, TUBG1, VEGFA and VEGFB; and

[0019] 5) A method for screening a personalized medicine for a cancer patient is provided, comprising a step of measuring the expression level of the amplified target gene in step 4) above and then comparing the expression level of the target gene in normal cells, cancer cells, and cancer cells treated with a cancer treatment candidate drug.

[0020] The present invention utilizes quantitative real-time PCR (qPCR) to quantify and analyze expression changes in 87 genes targeted by US FDA-approved cancer treatments, as well as mutations in some of these genes. This analysis allows for convenient and high-accuracy profiling of individual cancer patient expression patterns, thereby providing information for personalized drug selection. Therefore, the present invention can be utilized for personalized treatment by selectively administering existing or future cancer treatments to cancer patients.

[0021] FIG. 1A and FIG. 1B are graphs showing the expression patterns of 87 target genes by performing qPCR on normal tissue and cancer tissue samples collected from three renal cancer patients, respectively, according to one embodiment of the present invention. The first N and T are normal tissue (N) and cancer tissue (T) samples from renal cancer patient No. 1, the second N and T are normal tissue (N) and cancer tissue (T) samples from renal cancer patient No. 2, and the third N and T are normal tissue (N) and cancer tissue (T) samples from renal cancer patient No. 3.

[0022] Figures 2a and 2b are graphs showing the expression patterns of 87 target genes by performing qPCR on the normal human kidney cell line HK-2 and the renal cancer cell lines Caki-1, Caki-2, and ACHN, respectively. The first bar graph is the HK-2 cell line, the second bar graph is the Caki-1 cell line, the third bar graph is the Caki-2 cell line, and the fourth bar graph is the ACHN cell line.

[0023] Figure 3 shows the cell viability after treating renal cell carcinoma cell lines Caki-1, Caki-2, and ACHN with regorafenib at different concentrations.

[0024] Figure 4 is a diagram showing the tumor size after administering regorafenib to a mouse model transplanted with a renal cell line ACHN.

[0025] FIG. 5 is a graph showing the expression patterns of 87 target genes by performing qPCR on each of normal tissue and ascites samples collected from one gastric cancer patient showing symptoms of malignant ascites according to one embodiment of the present invention, wherein the first bar graph is an ascites sample, and the second to sixth bar graphs are normal tissue samples.

[0026] FIG. 6 is a diagram showing the cell viability after treating cancer cells derived from ascites samples collected from a gastric cancer patient showing symptoms of malignant ascites with different concentrations of carfilzomib or with different concentrations of ramucirumab and paclitaxel, according to one embodiment of the present invention.

[0027] Hereinafter, the present invention will be described in more detail.

[0028] The present invention relates to ACPP, ADA, ALK, BCR-ABL-1, BTK, CDK4, CDK6, CD19, CD3D, CD52, C-MET, CRBN, CTLA4, CYP17A1, DDR2, ERBB4, FCGR1A, FGF1, FGFR1, FGFR2, FGFR3, FRK, GNRH1, GNRHR, HDAC2, HDAC3, HPRT1, IFNAR1, IFNAR2, IL2RA, IL2RB, IL2RG, ITK, JAK1, JAK2, LDLR, LHCGR, LIMK1, MAP1A, MAP2, MAP2K1, MAP2K2, MAPK11, NEK11, NR3C1, NTRK1, PARP1, PARP2, PARP3, PDCD1, PGF, PIK3CD, PRLR, PSMB10, A kit for screening cancer patients with personalized medicine is provided, comprising primers or probes that specifically hybridize to each of at least two target genes selected from the group consisting of PSMB1, PSMB2, PSMB8, PSMB9, PSMD1, PSMD2, PTK6, RARA, RARB, RARG, RPL3, SH2B3, SIK1, SLC2A2, SMO, SSTR2, SSTR5, TEK, TLR8, TNFSF8, TNFSF11, TOP1MT, TOP2B, TUBA1A, TUBA4A, TUBB1, TUBB3, TUBB, TUBD1, TUBE1, TUBG1, VEGFA, and VEGFB.

[0029] In the present invention, the target genes include ACPP, ADA, ALK, BCR-ABL-1, BTK, CDK4, CDK6, CD19, CD3D, CD52, C-MET, CRBN, CTLA4, CYP17A1, DDR2, ERBB4, FCGR1A, FGF1, FGFR1, FGFR2, FGFR3, FRK, GNRH1, GNRHR, HDAC2, HDAC3, HPRT1, IFNAR1, IFNAR2, IL2RA, IL2RB, IL2RG, ITK, JAK1, JAK2, LDLR, LHCGR, LIMK1, MAP1A, MAP2, MAP2K1, MAP2K2, MAPK11, NEK11, NR3C1, NTRK1, PARP1, PARP2, PARP3, PDCD1, PGF, PIK3CD, At least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 selected from the group consisting of PRLR, PSMB10, PSMB1, PSMB2, PSMB8, PSMB9, PSMD1, PSMD2, PTK6, RARA, RARB, RARG, RPL3, SH2B3, SIK1, SLC2A2, SMO, SSTR2, SSTR5, TEK, TLR8, TNFSF8, TNFSF11, TOP1MT, TOP2B, TUBA1A, TUBA4A, TUBB1, TUBB3, TUBB, TUBD1, TUBE1, TUBG1, VEGFA and VEGFB. It may include, but is not limited to, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, or 45 targets, or all of the above targets.

[0030] In the present invention, the kit may be a kit for quantitative real-time PCR.

[0031] The term "primer" as used herein refers to a short nucleic acid sequence having a short free 3' terminal hydroxyl group that can form base pairs with a complementary template and serves as a starting point for copying the template strand. In other words, a primer refers to a single-stranded oligonucleotide that can initiate template-directed DNA synthesis under appropriate conditions (e.g., four different nucleoside triphosphates and DNA, a polymerizing agent such as a DNA polymerase enzyme) in an appropriate buffer and at an appropriate temperature.

[0032] The primers of the present invention can be chemically synthesized using the phosphoramidite solid support method or other well-known methods. In addition, such primers can be modified (e.g., additions, deletions, substitutions) using many means known in the art as long as it does not affect the detection of the target gene, and although they need not be perfectly complementary to the template, they must be sufficiently complementary to hybridize with the template. Non-limiting examples of such modifications include methylation, capping, substitution with one or more homologues of natural nucleotides, and modifications between nucleotides, such as modification with uncharged linkers (e.g., methyl phosphonate, phosphotriester, phosphoroamidate, carbamate, etc.) or charged linkers (e.g., phosphorothioate, phosphorodithioate, etc.). The nucleic acid may contain one or more additional covalently linked moieties, such as proteins (e.g., nucleases, toxins, antibodies, signal peptides, poly-L-lysine, etc.), intercalating agents (e.g., acridine, proralene, etc.), chelating agents (e.g., metals, radioactive metals, iron, oxidizing metals, etc.), and alkylating agents. The nucleic acid sequences of the present invention may also be modified with labels capable of directly or indirectly providing a detectable signal. Examples of labels include radioisotopes, fluorescent molecules, biotin, etc.

[0033] The term "probe" above means a linear oligomer of natural or modified monomers or linkages, comprising deoxyribonucleotides and ribonucleotides, capable of specifically hybridizing to a target nucleotide sequence, which may be naturally occurring or artificially synthesized.

[0034] The nucleotide sequence of the target of the present invention that should be referenced when producing the above primer or probe can be found in GenBank, and the primer or probe can be designed with reference to this sequence.

[0035] For example, the primer set in [Table 1] below can be used as a primer set that specifically hybridizes to each target gene of the present invention, and can be specifically used for quantitative real-time PCR.

[0036] Specifically, the target genes ACPP, ADA, ALK, BCR-ABL-1, BTK, CDK4, CDK6, CD19, CD3D, CD52, C-MET, CRBN, CTLA4, CYP17A1, DDR2, ERBB4, FCGR1A, FGF1, FGFR1, FGFR2, FGFR3, FRK, GNRH1, GNRHR, HDAC2, HDAC3, HPRT1, IFNAR1, IFNAR2, IL2RA, IL2RB, IL2RG, ITK, JAK1, JAK2, LDLR, LHCGR, LIMK1, MAP1A, MAP2, MAP2K1, MAP2K2, MAPK11, NEK11, NR3C1, NTRK1, PARP1, PARP2, PARP3, PDCD1, PGF, PIK3CD, PRLR, The primers that specifically hybridize to each of PSMB10, PSMB1, PSMB2, PSMB8, PSMB9, PSMD1, PSMD2, PTK6, RARA, RARB, RARG, RPL3, SH2B3, SIK1, SLC2A2, SMO, SSTR2, SSTR5, TEK, TLR8, TNFSF8, TNFSF11, TOP1MT, TOP2B, TUBA1A, TUBA4A, TUBB1, TUBB3, TUBB, TUBD1, TUBE1, TUBG1, VEGFA and VEGFB may be selected from the group consisting of primers represented by SEQ ID NOs: 1 to 174 in [Table 1] below. More specifically, the target genes ACPP, ADA, ALK, BCR-ABL-1, BTK, CDK4, CDK6, CD19, CD3D, CD52, C-MET, CRBN, CTLA4, CYP17A1, DDR2, ERBB4, FCGR1A, FGF1, FGFR1, FGFR2, FGFR3, FRK, GNRH1, GNRHR, HDAC2, HDAC3, HPRT1, IFNAR1, IFNAR2, IL2RA, IL2RB, IL2RG, ITK, JAK1, JAK2, LDLR, LHCGR, LIMK1, MAP1A, MAP2, MAP2K1, MAP2K2, MAPK11, NEK11,Each primer that specifically hybridizes to NR3C1, NTRK1, PARP1, PARP2, PARP3, PDCD1, PGF, PIK3CD, PRLR, PSMB10, PSMB1, PSMB2, PSMB8, PSMB9, PSMD1, PSMD2, PTK6, RARA, RARB, RARG, RPL3, SH2B3, SIK1, SLC2A2, SMO, SSTR2, SSTR5, TEK, TLR8, TNFSF8, TNFSF11, TOP1MT, TOP2B, TUBA1A, TUBA4A, TUBB1, TUBB3, TUBB, TUBD1, TUBE1, TUBG1, VEGFA and VEGFB comprises a primer set consisting of the base sequences of SEQ ID NOs: 1 and 2; a primer set consisting of the base sequences of SEQ ID NOs: 3 and 4; A primer set consisting of the base sequences of SEQ ID NOs: 5 and 6; A primer set consisting of the base sequences of SEQ ID NOs: 7 and 8; A primer set consisting of the base sequences of SEQ ID NOs: 9 and 10; A primer set consisting of the base sequences of SEQ ID NOs: 11 and 12; A primer set consisting of the base sequences of SEQ ID NOs: 13 and 14; A primer set consisting of the base sequences of SEQ ID NOs: 15 and 16; A primer set consisting of the base sequences of SEQ ID NOs: 17 and 18; A primer set consisting of the base sequences of SEQ ID NOs: 19 and 20; A primer set consisting of the base sequences of SEQ ID NOs: 21 and 22; A primer set consisting of the base sequences of SEQ ID NOs: 23 and 24; A primer set consisting of the base sequences of SEQ ID NOs: 25 and 26; A primer set consisting of the base sequences of SEQ ID NOs: 27 and 28; A primer set consisting of the base sequences of SEQ ID NOs: 29 and 30; A primer set consisting of the base sequences of SEQ ID NOs: 31 and 32; a primer set consisting of the base sequences of SEQ ID NOs: 33 and 34; a primer set consisting of the base sequences of SEQ ID NOs: 35 and 36; a primer set consisting of the base sequences of SEQ ID NOs: 37 and 38; a primer set consisting of the base sequences of SEQ ID NOs: 39 and 40; a primer set consisting of the base sequences of SEQ ID NOs: 41 andA primer set consisting of the nucleotide sequence of SEQ ID NO: 42; A primer set consisting of the nucleotide sequences of SEQ ID NO: 43 and 44; A primer set consisting of the nucleotide sequences of SEQ ID NO: 45 and 46; A primer set consisting of the nucleotide sequences of SEQ ID NO: 47 and 48; A primer set consisting of the nucleotide sequences of SEQ ID NO: 49 and 50; A primer set consisting of the nucleotide sequences of SEQ ID NO: 51 and 52; A primer set consisting of the nucleotide sequences of SEQ ID NO: 53 and 54; A primer set consisting of the nucleotide sequences of SEQ ID NO: 55 and 56; A primer set consisting of the nucleotide sequences of SEQ ID NO: 57 and 58; A primer set consisting of the nucleotide sequences of SEQ ID NO: 59 and 60; A primer set consisting of the nucleotide sequences of SEQ ID NO: 61 and 62; A primer set consisting of the nucleotide sequences of SEQ ID NO: 63 and 64; A primer set consisting of the nucleotide sequences of SEQ ID NO: 65 and 66; A primer set consisting of the nucleotide sequences of SEQ ID NOs: 67 and 68; A primer set consisting of the nucleotide sequences of SEQ ID NOs: 69 and 70; A primer set consisting of the nucleotide sequences of SEQ ID NOs: 71 and 72; A primer set consisting of the nucleotide sequences of SEQ ID NOs: 73 and 74; A primer set consisting of the nucleotide sequences of SEQ ID NOs: 75 and 76; A primer set consisting of the nucleotide sequences of SEQ ID NOs: 77 and 78; A primer set consisting of the nucleotide sequences of SEQ ID NOs: 79 and 80; A primer set consisting of the nucleotide sequences of SEQ ID NOs: 81 and 82; A primer set consisting of the nucleotide sequences of SEQ ID NOs: 83 and 84; A primer set consisting of the nucleotide sequences of SEQ ID NOs: 85 and 86; A primer set consisting of the nucleotide sequences of SEQ ID NOs: 87 and 88; A primer set consisting of the nucleotide sequences of SEQ ID NOs: 89 and 90; A primer set consisting of the nucleotide sequences of SEQ ID NOs: 91 and 92; A primer set consisting of the base sequences of SEQ ID NOs: 93 and 94; a primer set consisting of the base sequences of SEQ ID NOs: 95 and 96; a primer set consisting of the base sequences of SEQ ID NOs: 97 and 98; and a primer set consisting of the base sequences of SEQ ID NOs: 101 and 102.A primer set comprising: a primer set comprising the base sequences of SEQ ID NOs: 103 and 104; a primer set comprising the base sequences of SEQ ID NOs: 105 and 106; a primer set comprising the base sequences of SEQ ID NOs: 107 and 108; a primer set comprising the base sequences of SEQ ID NOs: 109 and 110; a primer set comprising the base sequences of SEQ ID NOs: 111 and 112; a primer set comprising the base sequences of SEQ ID NOs: 113 and 114; a primer set comprising the base sequences of SEQ ID NOs: 115 and 116; a primer set comprising the base sequences of SEQ ID NOs: 117 and 118; a primer set comprising the base sequences of SEQ ID NOs: 119 and 120; a primer set comprising the base sequences of SEQ ID NOs: 121 and 122; a primer set comprising the base sequences of SEQ ID NOs: 123 and 124; A primer set consisting of the base sequences of SEQ ID NOs: 125 and 126; A primer set consisting of the base sequences of SEQ ID NOs: 127 and 128; A primer set consisting of the base sequences of SEQ ID NOs: 129 and 130; A primer set consisting of the base sequences of SEQ ID NOs: 131 and 132; A primer set consisting of the base sequences of SEQ ID NOs: 133 and 134; A primer set consisting of the base sequences of SEQ ID NOs: 135 and 136; A primer set consisting of the base sequences of SEQ ID NOs: 137 and 138; A primer set consisting of the base sequences of SEQ ID NOs: 139 and 140; A primer set consisting of the base sequences of SEQ ID NOs: 141 and 142; A primer set consisting of the base sequences of SEQ ID NOs: 143 and 144; A primer set consisting of the base sequences of SEQ ID NOs: 145 and 146; A primer set consisting of the base sequences of SEQ ID NOs: 147 and 148; A primer set consisting of the base sequences of SEQ ID NOs: 149 and 150; a primer set consisting of the base sequences of SEQ ID NOs: 151 and 152; a primer set consisting of the base sequences of SEQ ID NOs: 153 and 154; a primer set consisting of the base sequences of SEQ ID NOs: 155 and 156; a primer set consisting of the base sequences of SEQ ID NOs: 157 andA primer set consisting of the base sequence of 158; a primer set consisting of the base sequences of SEQ ID NOs: 159 and 160; a primer set consisting of the base sequences of SEQ ID NOs: 161 and 162; a primer set consisting of the base sequences of SEQ ID NOs: 163 and 164; a primer set consisting of the base sequences of SEQ ID NOs: 165 and 166; a primer set consisting of the base sequences of SEQ ID NOs: 167 and 168; a primer set consisting of the base sequences of SEQ ID NOs: 169 and 170; a primer set consisting of the base sequences of SEQ ID NOs: 171 and 172; a primer set consisting of the base sequences of SEQ ID NOs: 173 and 174.

[0037] In the present invention, the cancer may be kidney cancer, stomach cancer, lung cancer, breast cancer, ovarian cancer, liver cancer, bronchial cancer, lymphoma, nasopharyngeal cancer, laryngeal cancer, pancreatic cancer, bladder cancer, colon cancer, colon cancer, cervical cancer, brain cancer, prostate cancer, bone cancer, head and neck cancer, skin cancer, thyroid cancer, parathyroid cancer, ureteral cancer, or blood cancer, and may be specifically kidney cancer, but is not limited thereto.

[0038] Additionally, the cancer patient may have symptoms of terminal cancer patients, regardless of the type of cancer, such as, but not limited to, ascites or BAL fluid (pleural effusion).

[0039] In the present invention, the kit may include DNA polymerase, dNTPs, a buffer, etc. to perform a PCR amplification reaction. The kit may further include a user guide describing optimal reaction conditions. The guide is a printed matter explaining how to use the kit, such as methods for preparing reverse transcription buffer and PCR buffer, and suggested reaction conditions. The guide includes instructions in the form of a pamphlet or leaflet, a label attached to the kit, and on the surface of the package containing the kit. The guide also includes information disclosed or provided through electronic media, such as the Internet.

[0040]

[0041] In addition, the present invention

[0042] 1) ACPP, ADA, ALK, BCR-ABL-1, BTK, CDK4, CDK6, CD19, CD3D, CD52, C-MET, CRBN, CTLA4, CYP17A1, DDR2, ERBB4, FCGR1A, FGF1, FGFR1, FGFR2, FGFR3, FRK, GNRH1, GNRHR, HDAC2, HDAC3, HPRT1, IFNAR1, IFNAR2, IL2RA, IL2RB, IL2RG, ITK, JAK1, JAK2, LDLR, LHCGR, LIMK1, MAP1A, MAP2, MAP2K1, MAP2K2, MAPK11, NEK11, NR3C1, NTRK1, PARP1, PARP2, PARP3, PDCD1, PGF, PIK3CD, A step of measuring the expression of at least two target genes selected from the group consisting of PRLR, PSMB10, PSMB1, PSMB2, PSMB8, PSMB9, PSMD1, PSMD2, PTK6, RARA, RARB, RARG, RPL3, SH2B3, SIK1, SLC2A2, SMO, SSTR2, SSTR5, TEK, TLR8, TNFSF8, TNFSF11, TOP1MT, TOP2B, TUBA1A, TUBA4A, TUBB1, TUBB3, TUBB, TUBD1, TUBE1, TUBG1, VEGFA and VEGFB; and

[0043] 2) A method for screening a drug tailored to a cancer patient is provided, including a step of screening a drug that acts on a target gene measured to be highly expressed in step 1).

[0044] In the method of the present invention, the biological sample in step 1) includes various biological samples, specifically blood, serum, plasma, tissue, cell, lymph, bone marrow fluid, saliva, urine, feces, ocular fluid, semen, brain extract, spinal fluid, synovial fluid, thymic fluid, ascites or amniotic fluid, more specifically tissue or cell, and even more specifically cancer tissue or cancer cell.

[0045] In the method of the present invention, in the step 1), the target genes include ACPP, ADA, ALK, BCR-ABL-1, BTK, CDK4, CDK6, CD19, CD3D, CD52, C-MET, CRBN, CTLA4, CYP17A1, DDR2, ERBB4, FCGR1A, FGF1, FGFR1, FGFR2, FGFR3, FRK, GNRH1, GNRHR, HDAC2, HDAC3, HPRT1, IFNAR1, IFNAR2, IL2RA, IL2RB, IL2RG, ITK, JAK1, JAK2, LDLR, LHCGR, LIMK1, MAP1A, MAP2, MAP2K1, MAP2K2, MAPK11, NEK11, NR3C1, NTRK1, PARP1, PARP2, PARP3, PDCD1, PGF, At least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 selected from the group consisting of PIK3CD, PRLR, PSMB10, PSMB1, PSMB2, PSMB8, PSMB9, PSMD1, PSMD2, PTK6, RARA, RARB, RARG, RPL3, SH2B3, SIK1, SLC2A2, SMO, SSTR2, SSTR5, TEK, TLR8, TNFSF8, TNFSF11, TOP1MT, TOP2B, TUBA1A, TUBA4A, TUBB1, TUBB3, TUBB, TUBD1, TUBE1, TUBG1, VEGFA and VEGFB. It may include, but is not limited to, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, or 45 target genes, or all of the above targets.

[0046] In the method of the present invention, the measurement of gene expression in step 1) can be performed according to a quantitative real-time PCR method.

[0047] In the method of the present invention, the drug acting on the target gene in step 2) may be, but is not limited to, a cancer treatment approved by the US FDA or the European EMA and currently in clinical use. For example, cancer treatment drugs approved by the US FDA and currently in clinical use are described in The Author(s) BMC Systems Biology 2017, 11(Suppl 5):87.

[0048] In addition, the present invention

[0049] 1) A step of isolating and proliferating cancer cells and normal cells from cancer tissue and normal tissue isolated from a cancer patient;

[0050] 2) A step of treating the cancer cells of step 1) with a cancer treatment candidate drug;

[0051] 3) A step of isolating total RNA from the cancer cells and normal cells of step 1) and the cancer cells treated with the cancer treatment candidate drug of step 2), and synthesizing cDNA using the total RNA as a template;

[0052] 4) Using the cDNA synthesized in the above step 3) as a template, ACPP, ADA, ALK, BCR-ABL-1, BTK, CDK4, CDK6, CD19, CD3D, CD52, C-MET, CRBN, CTLA4, CYP17A1, DDR2, ERBB4, FCGR1A, FGF1, FGFR1, FGFR2, FGFR3, FRK, GNRH1, GNRHR, HDAC2, HDAC3, HPRT1, IFNAR1, IFNAR2, IL2RA, IL2RB, IL2RG, ITK, JAK1, JAK2, LDLR, LHCGR, LIMK1, MAP1A, MAP2, MAP2K1, MAP2K2, MAPK11, NEK11, NR3C1, NTRK1, PARP1, PARP2, PARP3, PDCD1, A step of amplifying a target gene using primers or probes that specifically hybridize to each of at least two target genes selected from the group consisting of PGF, PIK3CD, PRLR, PSMB10, PSMB1, PSMB2, PSMB8, PSMB9, PSMD1, PSMD2, PTK6, RARA, RARB, RARG, RPL3, SH2B3, SIK1, SLC2A2, SMO, SSTR2, SSTR5, TEK, TLR8, TNFSF8, TNFSF11, TOP1MT, TOP2B, TUBA1A, TUBA4A, TUBB1, TUBB3, TUBB, TUBD1, TUBE1, TUBG1, VEGFA and VEGFB; and

[0053] 5) A method for screening a personalized medicine for a cancer patient is provided, comprising a step of measuring the expression level of the amplified target gene in step 4) above and then comparing the expression level of the target gene in normal cells, cancer cells, and cancer cells treated with a cancer treatment candidate drug.

[0054] In the method of the present invention, the method of separating cancer cells and normal cells from cancer tissue and normal tissue separated from a cancer patient in step 1) may use any method known in the art, for example, the cancer tissue or normal tissue may be decomposed using a tissue-decomposing enzyme or a mechanical method, and the tissue-decomposed cancer cells may be separated according to cell size, density, or surface characteristics using a density gradient separation method, separation using a cell sorter, or a magnetic separation method.

[0055] In the method of the present invention, the cancer treatment candidate agent in step 2) includes any substance, molecule, element, compound, entity, or a combination thereof. For example, but not limited to, it includes a protein, a polypeptide, a small organic molecule, a polysaccharide, a polynucleotide, etc. It may also be a natural product, a synthetic compound, a chemical compound, or a combination of two or more substances. Specific examples include polypeptides, beta-turn mimetics, polysaccharides, phospholipids, hormones, prostaglandins, steroids, aromatic compounds, heterocyclic compounds, benzodiazepines, oligomeric N-substituted glycines, oligocarbamates, saccharides, fatty acids, purines, pyrimidines or derivatives, structural analogs or combinations thereof, and may be synthetic substances, while other candidate agents may be natural substances.

[0056] In the method of the present invention, the method for isolating total RNA in step 3) may use any method known in the art, for example, a phenol extraction method may be used.

[0057] In the method of the present invention, in step 4), ACPP, ADA, ALK, BCR-ABL-1, BTK, CDK4, CDK6, CD19, CD3D, CD52, C-MET, CRBN, CTLA4, CYP17A1, DDR2, ERBB4, FCGR1A, FGF1, FGFR1, FGFR2, FGFR3, FRK, GNRH1, GNRHR, HDAC2, HDAC3, HPRT1, IFNAR1, IFNAR2, IL2RA, IL2RB, IL2RG, ITK, JAK1, JAK2, LDLR, LHCGR, LIMK1, MAP1A, MAP2, MAP2K1, MAP2K2, MAPK11, NEK11, NR3C1, NTRK1, PARP1, PARP2, PARP3, PDCD1, PGF, At least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 selected from the group consisting of PIK3CD, PRLR, PSMB10, PSMB1, PSMB2, PSMB8, PSMB9, PSMD1, PSMD2, PTK6, RARA, RARB, RARG, RPL3, SH2B3, SIK1, SLC2A2, SMO, SSTR2, SSTR5, TEK, TLR8, TNFSF8, TNFSF11, TOP1MT, TOP2B, TUBA1A, TUBA4A, TUBB1, TUBB3, TUBB, TUBD1, TUBE1, TUBG1, VEGFA and VEGFB. It may include, but is not limited to, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, or 45 target genes, or may include all of the target genes.

[0058] Additionally, in the above step 4), the primer or probe may be a primer or probe for quantitative real-time PCR.

[0059] In the method of the present invention, a candidate drug that increases in the amount of expression of the target gene amplified in step 5) compared to normal cells in cancer cells and decreases in cancer cells treated with the candidate anticancer drug compared to cancer cells can be selected as a personalized medicine for cancer patients.

[0060] Hereinafter, the present invention will be described in detail by examples.

[0061] However, the following examples are only illustrative of the present invention, and the content of the present invention is not limited to the following examples.

[0062] <Example 1> Preparation of kidney cancer patient samples

[0063] Normal and cancer tissue samples from three patients with renal cell carcinoma were obtained from the specimen bank of the Department of Pathology, Wonju Severance Christian Hospital. The three pairs of normal and cancer tissue samples were stored in cryotubes at -70°C until RNA extraction. Total RNA was extracted using a commercially available RNeasy Midi Kit (Qiagen, Chatsworth, CA, USA) according to the manufacturer's instructions. The quantity and quality of the extracted total RNA were assessed using ultraviolet spectrophotometry (DU 530, Beckmann, USA).

[0064] Reverse transcription was performed on 2 μg of extracted total RNA in a volume of 20 μl under conditions of 2 units of DNAse I (4.2 μM MgCl2). The reaction solution had the following composition: 2 μg of total RNA, 3.68 μl of 50 mM MgCl2, 0.96 μl of DNAse I, and the reaction volume was adjusted to 20 μl with DEPC-water.

[0065] For the previously DNAse I-treated samples, reverse transcription was performed using the Superscript II Reverse transcription Kit (Invitrogen cat# 18064-071) under the following conditions: 5X First Strand buffer 20 μl, 100 mM DTT 10 μl, 10 mM dNTPs 20 μl, pdN6 (1.6 μg / μl) 5 μl, RTase (200 U / μl) 0.5 μl, RNA 20 μl, and DEPC-water 24.5 μluL. Total reaction volume 100 μl.

[0066] The reverse transcription reaction was performed under the following temperature conditions: 25℃ 10 min, 42℃ 50 min, 72℃ 10 min, 4℃ hold.

[0067] After the reverse transcription reaction was completed, cDNA was adjusted to 5 ng / μl using DEPC-water.

[0068] <Example 2> Quantitative real-time PCR analysis for personalized drug screening for cancer patients

[0069] In order to screen for personalized medicine for cancer patients, the cDNA obtained in the above <Example 1> was used as a template, and the mRNA expression profiles of the 87 targets were completed using the quantitative real-time PCR (qPCR) method using primers for the 87 target genes in [Table 1] below.

[0070] Specifically, 87 molecular biological targets suitable for the present invention were selected from the therapeutic targets of approximately 300 cancer treatments approved by the US FDA or the European EMA, such as renal cancer treatment agents, such as everolimus, an mTOR inhibitor, and qPCR primers for the targets were designed as shown in [Table 1] below.

[0071] NumberGene nameDisclosure statusGenBank Accession numberPrimer sequence (5'→3')1ACPPNoNM_001099(Forward) TTGTACTTTGAGAAGGGGGAGT(SEQ ID NO: 1)(Reverse) GGTAGCATGAGGGGATACGG(SEQ ID NO: 2)2ADANoNM_000022(Forward) AAGAGGAGTTTAAAAGGCTGAACA(SEQ ID NO: 3)(Reverse) AAGGTGGCATCCCATAGGC(SEQ ID NO: 4)3ALKNoNM_004304(Forward) ATTGGAGACTTCGGGATGGC(SEQ ID NO: 5)(Reverse) CTTAACTGGCAGCATGGCAC(SEQ ID NO: 6)4BCR-ABL-1NoNM_005157(Forward) GGCCAGTGGAGATAACACTCTAA(SEQ ID NO: 7)(Reverse) CACCATTCCCCATTGTGATTATA(SEQ ID NO: 8)5BTKNoNM_000061(Forward) AGAAGCACCTTTTCAGCACCA(SEQ ID NO: 9)(Reverse) ACACTGGATATTTGAGCCTGGAT(SEQ ID NO: 10)6CD19NoNM_001178098(Forward) ATGAAGAGCTGACCCAGCCG(SEQ ID NO: 11)(Reverse) CCTCATAGGACTGGGACCCT(SEQ ID NO: 12)7CD3DNoNM_000732(Forward) GAACATAGCACGTTTCTCTCTGG(SEQ ID NO: 13)(Reverse) GTATCTTGAAGGGGCTCACTTG(SEQ ID NO: 14)8CD52NoNM_001803(Forward) TTCCTCTTCCTCCTACTCACCA(SEQ ID NO: 15)(Reverse) CTGGTGTCGTTTTGTCCTGA (SEQ ID NO: 16) 9CDK4NoNM_000075 (Forward) TTTGTGGCCCTCAAGAGTGT (SEQ ID NO: 17) (Reverse) ACGTCCATCAGCCGGACAAC (SEQ ID NO: 18) 10CDK6NoNM_001145306 (Forward) TCTTGCTCCAGTCCAGCTAC (SEQ ID NO: 19) (Reverse) GGGAGTCCAATCACGTCCAAG (SEQ ID NO:20)11C-METNoNM_001127500(Forward) GGACATCAGAGGGTCGCTT(SEQ ID NO: 21)(Reverse) GATGGGAGTCCAGGAGAAAAT(SEQ ID NO: 22)12CRBNNoNM_016302(Forward) GACGCTGCGCACAACAT(SEQ ID NO: 23)(Reverse) CTGGTCTTCAACTTCCATTTCATC(SEQ ID NO: 24)13CTLA4NoNM_005214(Forward) GTACCCACCGCCATACTACC(SEQ ID NO: 25)(Reverse) GCATTTTCACATAGACCCCTG(SEQ ID NO: 26)14CYP17A1NoNM_000102(Forward) GTTCAAGGATGGCGATCAG(SEQ ID NO: 27)(Reverse) GGCCAGCATATCACACAATGT(SEQ ID NO: 28)15DDR2NoNM_001014796(Forward) CCCAGGAAACTCCTAACTTTCAA(SEQ ID NO: 29)(Reverse) TCCCTCCACTTCACAGAGATG(SEQ ID NO: 30)16ERBB4NoNM_005235(Forward) GAACAGCAGTACCGAGCCTT(SEQ ID NO: 31)(Reverse) ACTTCTCGAACAGACCGCAG(SEQ ID NO: 32)17FCGR1ANoNM_00137880(Forward) TCCTTAAGCGCAGCCCT(SEQ ID NO: 33)(Reverse) AGGACATGAAACCAGACAGGA(SEQ ID NO: 34)18FGF1NoNM_000800(Forward) GGGCTTTTATACGGCTCACAGAC(SEQ ID NO: 35)(Reverse) AATGGTTCTCCTCCAGCCTT(SEQ ID NO: 36)19FGFR1NoNM_023110(Forward) GACGCAGGGGAGTATACGTG(SEQ ID NO: 37)(Reverse) TCTCTTCCAGGGCTTCCAGA(SEQ ID NO: 38)20FGFR2NoNM_000141(Forward) CACGACCAAGAAGCCAGACT(SEQ ID NO: 39)(Reverse) TGGACTCAGCCGAAACTGTTA(SEQ ID NO:40)21FGFR3NoNM_000142(Forward) GAATGCCTCCCACGAGGAC(SEQ ID NO: 41)(Reverse) GAGGATGGAGCGTCTGTCAC(SEQ ID NO: 42)22FRKNoNM_002031(Forward) CCGATGTATGGTCATTTGGAAT(SEQ ID NO: 43)(Reverse) CTGGATTACCTGGGCACCT(SEQ ID NO: 44)23GNRH1NoNM_000825(Forward) GGTTGGTCAACTGGCAGAAAC(SEQ ID NO: 45)(Reverse) AGAGCTCCTTTCAGGTCTCG(SEQ ID NO: 46)24GNRHRNoNM_000406(Forward) ATCTTCACCCTGACACGGG(SEQ ID NO: 47)(Reverse) TTAGAGTCTTCAGCCGTGCTC(SEQ ID NO: 48)25HDAC2NoNM_001527(Forward) TCTGCTACTACTACGACGGTGAT(SEQ ID NO: 49)(Reverse) CAGTGGCTTTATGGGGCCTA(SEQ ID NO: 50)26HDAC3NoNM_001355039(Forward) TGGCATTGATGACCAGAGTTACA(SEQ ID NO: 51)(Reverse) TGCACGTGGGTTGGTAGAAG(SEQ ID NO: 52)27HPRT1NoNM_000194(Forward) CTGGCGTCGTGATTAGTGAT(SEQ ID NO: 53)(Reverse) GAGCAAGACGTTCAGTCCTGT(SEQ ID NO: 54)28IFNAR1NoNM_001384498(Forward) TGCTGCGAAAGTCTTCTTGAG(SEQ ID NO: 55)(Reverse) TGGCTGTTCAGAGAAATACTCATC(SEQ ID NO: 56)29IFNAR2NoNM_207585(Forward) TGAGCCAGAATGCCTTCATC(SEQ ID NO: 57)(Reverse) AGATTCATCTGTGTAATCAGGCG(SEQ ID NO: 58)30IL2RANoNM_000417(Forward) GAATGCAAGAGAGGTTTCCGC(SEQ ID NO: 59)(Reverse) TGTTCCGAGTGGCAGAGCTT(SEQ ID NO:60)31IL2RBNoNM_000878(Forward) ACACTTCCTGCCAAGTCCA(SEQ ID NO: 61)(Reverse) ATGCTTGACTCACGGGGA(SEQ ID NO: 62)32IL2RGNoNM_000206(Forward) ATTTCTGGCTGGAACGGACG(SEQ ID NO: 63)(Reverse) GCCAGTCCCTTAGACACACC(SEQ ID NO: 64)33ITKNoNM_005546(Forward) CCTCCTACTCCTGAAGACAACAG(SEQ ID NO: 65)(Reverse) TGAGGATCATTGGTTTGGTAGTC(SEQ ID NO: 66)34JAK1NoNM_002227(Forward) CACAGGCATGCCGTATCTCT(SEQ ID NO: 67)(Reverse) CCAGAGCTTGGTGTTCTCGT(SEQ ID NO: 68)35JAK2NoNM_004972(Forward) TGCTGCTTCTAAAGCTTGTGGTAT(SEQ ID NO: 69)(Reverse) GGAAGACATGGTTGGGTGGAT(SEQ ID NO: 70)36LDLRNoNM_000527(Forward) TGACAATGTCTCACCAAGCTCT(SEQ ID NO: 71)(Reverse) GAGGACAATGGACAGAGCCC(SEQ ID NO: 72)37LHCGRNoNM_000233(Forward) CCATCTCAAGCTTTCAGAGGA(SEQ ID NO: 73)(Reverse) TAGCTTCTATCCTTTCCAGGGA(SEQ ID NO: 74)38LIMK1NoNM_002314(Forward) TGACACACCGTGAGACAGGT(SEQ ID NO: 75)(Reverse) GCATGACCTTCACCTCCTTGA (SEQ ID NO: 76) 39MAP1ANoNM_002373 (Forward) GGGAGAATCTTCAGGTGACTC (SEQ ID NO: 77) (Reverse) CCAGGACCAGGACATTCAGT (SEQ ID NO: 78) 40MAP2NoNM_002374 (Forward) CCATCACCTGCCTCAGAAC (SEQ ID NO: 79) (Reverse) AATACACTGGGAGCCAGAGC (SEQ ID NO: 80) 41MAP2K1NoNM_002755 (Forward)AGCTCTGCGGAGACCAACT(SEQ ID NO: 81)(Reverse) GCTGCTGCTCATCAAGCTCT(SEQ ID NO: 82)42MAP2K2NoNM_030662(Forward) TATATTGTGAACGAGCCACCTCC(SEQ ID NO: 83)(Reverse) TGGTTTGTGAGCATCTTCAGGT(SEQ ID NO: 84)43MAPK11NoNM_002751(Forward) CGAGGACTTCAGCGAAGTGTA(SEQ ID NO: 85)(Reverse) GCCGAGTGGATGTACTTCAG(SEQ ID NO: 86)44NEK11NoNM_024800(Forward) CCAAACGAGGAGAGGAATTAAAG(SEQ ID NO: 87)(Reverse) GCCTGTACAGTTTCATTTGGATTT(SEQ ID NO: 88)45NR3C1NoNM_000176(Forward) AAGTTTTCTTCAAAAGAGCAGTGG(SEQ ID NO: 89)(Reverse) TCGATGATGCAATCATTCCT(SEQ ID NO: 90)46NTRK1NoNM_001012331(Forward) TCTGGAGCTCCGTGATCTG(SEQ ID NO: 91)(Reverse) AGTGAAATGGAAGGCATCTGG(SEQ ID NO: 92)47PARP1NoNM_001618(Forward) ACTTTGCTGGGATCCTGTCC(SEQ ID NO: 93)(Reverse) CAAACATGTAGCCTGTCACGG(SEQ ID NO: 94)48PARP2NoNM_005484(Forward) TCACAGGTTACATGTTTGGGA(SEQ ID NO: 95)(Reverse) TTCATTACACTGACCTAGAGCTACC(SEQ ID NO: 96)49PARP3NoNM_001003931(Forward) CAAGAACAACTGGGCAGAGC(SEQ ID NO: 97)(Reverse) GGCCTCTGTCCACCTTCAC(SEQ ID NO: 98)50PDCD1NoNM_005018(Forward) ATAGGAGCCAGGCGCA(SEQ ID NO: 99)(Reverse) CCAGCTCCCCATAGTCCA(SEQ ID NO: 100)51PGFNoNM_002632(Forward)GAGCTGACGTTCTCTCAGCA(SEQ ID NO: 101)(Reverse) TACCTCCGGGGAACAGCAT(SEQ ID NO: 102)52PIK3CDNoNM_005026(Forward) CAGGCATGAGTACCTGTATGGC(SEQ ID NO: 103)(Reverse) CATGGTCAGGTGAGGGGT(SEQ ID NO: 104)53PRLRNoNM_000949(Forward) TGGTTCACGCTCCTGTATGA(SEQ ID NO: 105)(Reverse) CTCTGTTTGCTGCCCAGC(SEQ ID NO: 106)54PSMB10NoNM_002801(Forward) ACGGTCACTCGCATCCTG(SEQ ID NO: 107)(Reverse) GGTCCAGTCAGGTCTACGCC(SEQ ID NO: 108)55PSMB1NoNM_002793(Forward) CAATTCATACGCGGGATAGC(SEQ ID NO: 109)(Reverse) CCATGAAAACCGCTGCAT(SEQ ID NO: 110)56PSMB2NoNM_002794(Forward) TCACACGCCGAAACCTG(SEQ ID NO: 111)(Reverse) GGCCCTTCATGCTCATCATAG(SEQ ID NO: 112)57PSMB8NoNM_004159(Forward) GCAGCAGTGGATTCTCGG(SEQ ID NO: 113)(Reverse) GCAGGTAAGGGTTAATCTCAATCA(SEQ ID NO: 114)58PSMB9NoNM_002800(Forward) CATGGTAGCTGGCTGGGA(SEQ ID NO: 115)(Reverse) AAGGCTGTCGAGTCAGCATT(SEQ ID NO: 116)59PSMD1NoNM_002807(Forward) GGGACCTCTTCAATGTCAATGAT(SEQ ID NO: 117)(Reverse) TCCACACATTGTTTGGTGTAGTG(SEQ ID NO: 118)60PSMD2NoNM_002808(Forward) GGTGCCTGATGACATCTACAAA(SEQ ID NO: 119)(Reverse) GCAGAGTCCACCTGAGAGC(SEQ ID NO: 120)61PTK6NoNM_005975(Forward)GATCAGGGTCAGCGAGAAGC(SEQ ID NO: 121)(Reverse) CCGCCAGATCTTGTAGTGCC(SEQ ID NO: 122)62RARANoNM_000964(Forward) TTAGCCTGCCCTCTTTGGAC(SEQ ID NO: 123)(Reverse) TCAGAAGGGAGGCAGACAGT(SEQ ID NO: 124)63RARBNoNM_000965(Forward) AGCAAGCCTCACATGTTTCC(SEQ ID NO: 125)(Reverse) CAAGGTAATTACACGCTCTGC(SEQ ID NO: 126)64RARGNoNM_000966(Forward) AGCTCATCACCAAGGTCAGC(SEQ ID NO: 127)(Reverse) TCGTGGTATACTTGCCCAGC(SEQ ID NO: 128)65RPL3NoNM_000967(Forward) TACTGCCAAGTCATCCGTGTC(SEQ ID NO: 129)(Reverse) TCTCCATCAGGTGGGCCTTC(SEQ ID NO: 130)66SH2B3NoNM_005475(Forward) CCTGATGCTCATGGAGTGTTCC(SEQ ID NO: 131)(Reverse) GGAAAGTGGAGGTGCTGCACAC(SEQ ID NO: 132)67SIK1NoNM_173354(Forward) TTCTGCTCCCTGTCAGCTTCC(SEQ ID NO: 133)(Reverse) TCCCAGAAACCCTTTGGTCCG(SEQ ID NO: 134)68SLC2A2NoNM_000340(Forward) ATGTCAGTGGGACTTGTGCTGC(SEQ ID NO: 135)(Reverse) AACTCAGCCACCATGAACCAGG (SEQ ID NO: 136) 69SMONoNM_005631 (Forward) GAAGTGCCCTTGGTTCGGA (SEQ ID NO: 137) (Reverse) GCAGGGTAGCGATTCGAGTT (SEQ ID NO: 138) 70SSTR2NoNM_001050 (Forward) ACTCAATGGAAGCCACACATGG (SEQ ID NO: 139) (Reverse) TACGGCTCTGTCTGGTTTGAGG (SEQ ID NO: 140) 71SSTR5NoNM_001053 (Forward)CGTGGTCATCCTCTCCTACG(SEQ ID NO: 141)(Reverse) ACCTTCTGGAAGCTCTGGC(SEQ ID NO: 142)72TEKNoNM_000459(Forward) GTTGGCCTTTCTGATCATATTGC(SEQ ID NO: 143)(Reverse) CTGCACAGCTGGTTCTTCCC(SEQ ID NO: 144)73TLR8NoNM_016610(Forward) ATGTTCCTTCAGTCGTCAATGC(SEQ ID NO: 145)(Reverse) TTGCTGCACTCTGCAATAACT(SEQ ID NO: 146)74TNFSF8NoNM_001244(Forward) ATCTGTGCCACATCAGCCACCA(SEQ ID NO: 147)(Reverse) AAGGTGGTGTCCTTCTCAGCCA(SEQ ID NO: 148)75TNFSF11NoNM_003701(Forward) CAGCACATCAGAGCAGAGAAAG(SEQ ID NO: 149)(Reverse) AGCAAAAGGCTGAGCTTCAA(SEQ ID NO: 150)76TOP1MTNoNM_052963(Forward) CAGGGAGGAGAAGCAGAAGC(SEQ ID NO: 151)(Reverse) AGGCGGCTCAATCTTGAAGT(SEQ ID NO: 152)77TOP2BNoNM_001330700(Forward) ATGTCAGACGAATGCTAGATGG(SEQ ID NO: 153)(Reverse) CCAAGTTCTTGAATCGTGCC(SEQ ID NO: 154)78TUBA1ANoNM_006009(Forward) GCGTTTTGGAAAGATACCCA(SEQ ID NO: 155)(Reverse) TTGCCAATCTGGACACCA(SEQ ID NO: 156)79TUBA4ANoNM_006000(Forward) AGCTCTATTGCTTGGAACATGGG(SEQ ID NO: 157)(Reverse) CCCCTCCACCAATGGTCTTGT(SEQ ID NO: 158)80TUBB1NoNM_030773(Forward) GCGTGAAATTGTCCATATTCAGA(SEQ ID NO: 159)(Reverse) AATCATCTCCCAGAACTTGGCT(SEQ ID NO:160)81TUBB3NoNM_006086(Forward) GCCTGACAATTTCATCTTTGGTCA(SEQ ID NO: 161)(Reverse) CAGGCAGTCGCAGTTTTCAC(SEQ ID NO: 162)82TUBBNoNM_001293212(Forward) CAGCTGGACCGCATCTCT(SEQ ID NO: 163)(Reverse) AGATCCACCAGGATGGCA(SEQ ID NO: 164)83TUBD1NoNM_016261(Forward) ATATGATTGTTGGGAAGGCATG(SEQ ID NO: 165)(Reverse) AAGTCCTCTTCTTCGATTCCAA(SEQ ID NO: 166)84TUBE1NoNM_016262(Forward) TTCTGGGACCTGGCACTAAG(SEQ ID NO: 167)(Reverse) ATCACCAACCACTCTGGTGTC (SEQ ID NO: 168) 85TUBG1NoNM_001070 (Forward) GGAGAAAAGATCCATGAGGACA (SEQ ID NO: 169) (Reverse) CCCAGCAATGGAGTGACA (SEQ ID NO: 170) 86VEGFANoNM_001025366 (Forward) CTTGCCTTGCTGCTCTACCT (SEQ ID NO: 171) (Reverse) TCCATGAACTTCACCACTTCGT (SEQ ID NO: 172) 87VEGFBNoNM_001243733 (Forward) CTGACGATGGCCTGGAGTG (SEQ ID NO: 173) (Reverse) CGGGTACCGGATCATGAGGA (SEQ ID NO: 174)

[0072] Using the above primers, a qPCR reaction solution was prepared according to the composition shown in [Table 2] below. 10 μl of the qPCR reaction solution was dispensed into 384 wells, and qPCR was performed using an ABI 7900 HT instrument under the conditions shown in [Table 3] below. The amount of the gene was quantified using the SDS 2.4 software program.

[0073] reaction solution1X (μl)2X SYBR50.25μM Primer Mix1.2RNase-free water2.8Template1

[0074] PCR conditionStageStepTimeTempHold stage12 min50℃2 (Initial heating)10 min95℃PCR stage1 (Denaturation)15 sec40 cycles95℃2 (Annealing)1 min60℃Melt curve stage115 sec95℃21 min60℃3 (Dissociation)15 sec95℃

[0075] <Experimental Example 1> Target gene expression profiles in renal cell carcinoma patients using qPCR analysis

[0076] Using normal tissue and cancer tissue samples collected from the three renal cancer patients of <Example 1>, qPCR was performed using the method described in <Example 2> to complete the expression profile for 87 target genes (Fig. 1a and Fig. 1b).

[0077] As a result, as shown in Figures 1a and 1b, it was confirmed that there were differences in the expression patterns of 87 target genes between normal and cancerous tissues of renal cancer patients.

[0078] The above results suggest that even in patients with the same type of renal cell carcinoma, the expression of cancer treatment target genes differs for each patient, and that effective treatment can be achieved by identifying the individual expression pattern for each patient based on this.

[0079] <Experimental Example 2> Target gene expression profiles and personalized cancer drug screening for renal cell cancer using qPCR analysis.

[0080] <2-1> Target gene expression profiles in renal cancer cells using qPCR analysis

[0081] Using three types of renal cell carcinoma cell lines, Caki-1, Caki-2, and ACHN cells, samples were prepared in the same manner as described in <Example 1>, and qPCR was performed in the manner described in <Example 2> to complete the expression profile for 87 target genes (Figs. 2a and 2b). The HK-2 cell line, a cell line derived from normal human kidney tissue, was used as a control.

[0082] As a result, as shown in Figures 2a and 2b, it was confirmed that there were differences in the expression patterns of 87 target genes depending on the three types of renal cell carcinoma cell lines. In particular, it was confirmed that DDR2 expression was significantly high in the Caki-1 cell line, whereas it was not high in the Caki-2 and ACHN cell lines.

[0083] <2-2> Confirmation of in vitro and in vivo personalized cancer drug screening

[0084] In order to select a customized cancer drug based on gene expression patterns, the three types of renal cancer cell lines of Example <2-1> were treated with anticancer drugs and their sensitivity to the anticancer drugs was evaluated.

[0085] Specifically, three renal cell lines (Caki-1, Caki-2, and ACHN) were seeded at 4,000 to 5,000 cells per well in a 96-well plate, cultured for 24 hours, and then treated with regorafenib, an FDA-approved drug for the treatment of metastatic renal cell carcinoma, at a concentration of 0 to 100 μM. After 72 hours, the number of viable cells was quantified using Sulforhodamine B (SRB) dye (Fig. 3).

[0086] As a result, as shown in Fig. 3, it was confirmed that Caki-1 cells with high DDR2 expression had low sensitivity to regorafenib, whereas Caki-2 and ACHN cell lines with low DDR2 expression had high sensitivity to regorafenib.

[0087] Additionally, the sensitivity to regorafenib was evaluated in an ACHN cell line transplant tumor mouse model.

[0088] Specifically, animal experiments were performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care and Use Committee of Wonju Severance Christian Hospital (Approval No. YWC-190917-3). Tumor models for the experiments were 5 × 10 6 ACHN cell lines were prepared in syringes and then implanted subcutaneously into the right shoulder of 5-week-old male mice (BALB / c-nude mice (Orient Bio, Inc.) weighing 20-25 g). After 2 weeks, when the tumors reached a diameter of 0.5 cm, the control group (Vehicle, n = 5) was intravenously administered the vehicle, and the experimental group (n = 5) was intravenously administered 10 mg / kg regorafenib 3 times a week for a total of 4 weeks, and then the tumor sizes were measured (Fig. 4).

[0089] As a result, as shown in Fig. 4, it was confirmed that the cancer treatment effect of regorafenib was excellent in the experimental group.

[0090] The above results suggest that regorafenib is a suitable anticancer agent in renal cell carcinoma with low DDR2 expression.

[0091] <Experimental Example 3> Target gene expression profiles and personalized cancer drug screening in gastric cancer patients using qPCR analysis.

[0092] <3-1> Target gene expression profiles in gastric cancer patients using qPCR analysis

[0093] Ascites samples and normal tissue samples from a gastric cancer patient with malignant ascites were obtained from the specimen bank of the Department of Pathology at Wonju Severance Christian Hospital. Next, using the samples, samples were prepared using the same method as described in <Example 1> above, and qPCR was performed using the method described in <Example 2> above to profile the five target genes with the highest expression among 87 target genes (Fig. 5).

[0094] As a result, as shown in Fig. 5, the expression of five target genes, PSMB1, PSMB2, PSBM9, CD52, and FCGR1A, was high, and among these, PSMB1, PSMB2, and PSBM9 were confirmed to be targets of carfilzomib.

[0095] <3-2> Confirmation of in vitro and in vivo personalized cancer drug screening

[0096] The gastric cancer cells derived from the ascites sample of a gastric cancer patient showing the symptoms of malignant ascites of the above Example <3-1> were treated with an anticancer drug and the sensitivity to the anticancer drug was confirmed.

[0097] Specifically, gastric cancer cells derived from ascites samples of gastric cancer patients with malignant ascites symptoms in Example <3-1> were seeded at 4,000 to 5,000 per well and cultured for 24 hours, and then treated with carfilzomib, which was identified as an overexpressed gene targeting therapeutic agent in Example <3-2>, at a concentration of 0 to 100 μM for 16 hours. The control group was treated with ramucirumab and paclitaxel, anticancer drugs that gastric cancer patients with malignant ascites had been treated with, at a concentration of 0 to 100 μM for 24 hours. After completion of treatment, the number of living cells was quantified using SRB (Sulforhodamine B) dye (Fig. 6).

[0098] As a result, as shown in Fig. 6, it was confirmed that the cell viability reduction effect of the carfilzomib treatment group was significantly superior to that of the ramucirumab and paclitaxel treatment groups.

[0099] The above results suggest that even for the same type of cancer, the expression of the 87 cancer treatment target genes differs for each patient, and that by quantifying and analyzing the expression changes and mutations of some of these genes using the qPCR method, personalized cancer drugs can be conveniently selected for cancer patients with high accuracy.

[0100] The method for analyzing target gene expression patterns of cancer patients according to the present invention can be utilized for personalized treatment for each patient by providing information that can selectively administer existing or future cancer treatments to cancer patients.

Claims

1. ACPP, ADA, ALK, BCR-ABL-1, BTK, CDK4, CDK6, CD19, CD3D, CD52, C-MET, CRBN, CTLA4, CYP17A1, DDR2, ERBB4, FCGR1A, FGF1, FGFR1, FGFR2, FGFR3, FRK, GNRH1, GNRHR, HDAC2, HDAC3, HPRT1, IFNAR1, IFNAR2, IL2RA, IL2RB, IL2RG, ITK, JAK1, JAK2, LDLR, LHCGR, LIMK1, MAP1A, MAP2, MAP2K1, MAP2K2, MAPK11, NEK11, NR3C1, NTRK1, PARP1, PARP2, PARP3, PDCD1, PGF, PIK3CD, PRLR, A kit for screening a cancer patient for personalized medicine, comprising primers or probes that specifically hybridize to at least two target genes each selected from the group consisting of PSMB10, PSMB1, PSMB2, PSMB8, PSMB9, PSMD1, PSMD2, PTK6, RARA, RARB, RARG, RPL3, SH2B3, SIK1, SLC2A2, SMO, SSTR2, SSTR5, TEK, TLR8, TNFSF8, TNFSF11, TOP1MT, TOP2B, TUBA1A, TUBA4A, TUBB1, TUBB3, TUBB, TUBD1, TUBE1, TUBG1, VEGFA and VEGFB.

2. In the first paragraph, the target gene is ACPP, ADA, ALK, BCR-ABL-1, BTK, CDK4, CDK6, CD19, CD3D, CD52, C-MET, CRBN, CTLA4, CYP17A1, DDR2, ERBB4, FCGR1A, FGF1, FGFR1, FGFR2, FGFR3, FRK, GNRH1, GNRHR, HDAC2, HDAC3, HPRT1, IFNAR1, IFNAR2, IL2RA, IL2RB, IL2RG, ITK, JAK1, JAK2, LDLR, LHCGR, LIMK1, MAP1A, MAP2, MAP2K1, MAP2K2, MAPK11, NEK11, NR3C1, NTRK1, PARP1, PARP2, PARP3, PDCD1, PGF, A kit for screening a cancer patient's personalized medicine, characterized in that it comprises at least 10 target genes selected from the group consisting of PIK3CD, PRLR, PSMB10, PSMB1, PSMB2, PSMB8, PSMB9, PSMD1, PSMD2, PTK6, RARA, RARB, RARG, RPL3, SH2B3, SIK1, SLC2A2, SMO, SSTR2, SSTR5, TEK, TLR8, TNFSF8, TNFSF11, TOP1MT, TOP2B, TUBA1A, TUBA4A, TUBB1, TUBB3, TUBB, TUBD1, TUBE1, TUBG1, VEGFA and VEGFB.

3. In the second paragraph, the target genes include ACPP, ADA, ALK, BCR-ABL-1, BTK, CDK4, CDK6, CD19, CD3D, CD52, C-MET, CRBN, CTLA4, CYP17A1, DDR2, ERBB4, FCGR1A, FGF1, FGFR1, FGFR2, FGFR3, FRK, GNRH1, GNRHR, HDAC2, HDAC3, HPRT1, IFNAR1, IFNAR2, IL2RA, IL2RB, IL2RG, ITK, JAK1, JAK2, LDLR, LHCGR, LIMK1, MAP1A, MAP2, MAP2K1, MAP2K2, MAPK11, NEK11, NR3C1, NTRK1, PARP1, PARP2, PARP3, PDCD1, PGF, A kit for screening a cancer patient's personalized medicine, characterized in that it comprises at least 20 target genes selected from the group consisting of PIK3CD, PRLR, PSMB10, PSMB1, PSMB2, PSMB8, PSMB9, PSMD1, PSMD2, PTK6, RARA, RARB, RARG, RPL3, SH2B3, SIK1, SLC2A2, SMO, SSTR2, SSTR5, TEK, TLR8, TNFSF8, TNFSF11, TOP1MT, TOP2B, TUBA1A, TUBA4A, TUBB1, TUBB3, TUBB, TUBD1, TUBE1, TUBG1, VEGFA and VEGFB.

4. In the third paragraph, the target genes include ACPP, ADA, ALK, BCR-ABL-1, BTK, CDK4, CDK6, CD19, CD3D, CD52, C-MET, CRBN, CTLA4, CYP17A1, DDR2, ERBB4, FCGR1A, FGF1, FGFR1, FGFR2, FGFR3, FRK, GNRH1, GNRHR, HDAC2, HDAC3, HPRT1, IFNAR1, IFNAR2, IL2RA, IL2RB, IL2RG, ITK, JAK1, JAK2, LDLR, LHCGR, LIMK1, MAP1A, MAP2, MAP2K1, MAP2K2, MAPK11, NEK11, NR3C1, NTRK1, PARP1, PARP2, PARP3, PDCD1, PGF, A kit for screening a cancer patient's personalized medicine, characterized in that it comprises at least 25 target genes selected from the group consisting of PIK3CD, PRLR, PSMB10, PSMB1, PSMB2, PSMB8, PSMB9, PSMD1, PSMD2, PTK6, RARA, RARB, RARG, RPL3, SH2B3, SIK1, SLC2A2, SMO, SSTR2, SSTR5, TEK, TLR8, TNFSF8, TNFSF11, TOP1MT, TOP2B, TUBA1A, TUBA4A, TUBB1, TUBB3, TUBB, TUBD1, TUBE1, TUBG1, VEGFA and VEGFB.

5. In the fourth paragraph, the target genes include ACPP, ADA, ALK, BCR-ABL-1, BTK, CDK4, CDK6, CD19, CD3D, CD52, C-MET, CRBN, CTLA4, CYP17A1, DDR2, ERBB4, FCGR1A, FGF1, FGFR1, FGFR2, FGFR3, FRK, GNRH1, GNRHR, HDAC2, HDAC3, HPRT1, IFNAR1, IFNAR2, IL2RA, IL2RB, IL2RG, ITK, JAK1, JAK2, LDLR, LHCGR, LIMK1, MAP1A, MAP2, MAP2K1, MAP2K2, MAPK11, NEK11, NR3C1, NTRK1, PARP1, PARP2, PARP3, PDCD1, PGF, A kit for screening a cancer patient's personalized medicine, characterized in that it comprises at least 35 target genes selected from the group consisting of PIK3CD, PRLR, PSMB10, PSMB1, PSMB2, PSMB8, PSMB9, PSMD1, PSMD2, PTK6, RARA, RARB, RARG, RPL3, SH2B3, SIK1, SLC2A2, SMO, SSTR2, SSTR5, TEK, TLR8, TNFSF8, TNFSF11, TOP1MT, TOP2B, TUBA1A, TUBA4A, TUBB1, TUBB3, TUBB, TUBD1, TUBE1, TUBG1, VEGFA and VEGFB.

6. In the 5th paragraph, the target gene is ACPP, ADA, ALK, BCR-ABL-1, BTK, CDK4, CDK6, CD19, CD3D, CD52, C-MET, CRBN, CTLA4, CYP17A1, DDR2, ERBB4, FCGR1A, FGF1, FGFR1, FGFR2, FGFR3, FRK, GNRH1, GNRHR, HDAC2, HDAC3, HPRT1, IFNAR1, IFNAR2, IL2RA, IL2RB, IL2RG, ITK, JAK1, JAK2, LDLR, LHCGR, LIMK1, MAP1A, MAP2, MAP2K1, MAP2K2, MAPK11, NEK11, NR3C1, NTRK1, PARP1, PARP2, PARP3, PDCD1, PGF, A kit for screening a cancer patient's personalized medicine, characterized in that it comprises at least 45 target genes selected from the group consisting of PIK3CD, PRLR, PSMB10, PSMB1, PSMB2, PSMB8, PSMB9, PSMD1, PSMD2, PTK6, RARA, RARB, RARG, RPL3, SH2B3, SIK1, SLC2A2, SMO, SSTR2, SSTR5, TEK, TLR8, TNFSF8, TNFSF11, TOP1MT, TOP2B, TUBA1A, TUBA4A, TUBB1, TUBB3, TUBB, TUBD1, TUBE1, TUBG1, VEGFA and VEGFB.

7. A kit for screening a cancer patient-tailored medicine, characterized in that in paragraph 1, the primers that specifically hybridize to each of the target genes are selected from the group consisting of primers represented by SEQ ID NOs: 1 to 174.

8. A kit for screening customized medicine for cancer patients, characterized in that the kit in paragraph 1 is a kit for quantitative real-time PCR.

9. A kit for screening a cancer patient-tailored medicine, characterized in that in paragraph 1, the cancer is selected from the group consisting of kidney cancer, stomach cancer, lung cancer, breast cancer, ovarian cancer, liver cancer, bronchial cancer, lymphoma, nasopharyngeal cancer, laryngeal cancer, pancreatic cancer, bladder cancer, colon cancer, colon cancer, cervical cancer, brain cancer, prostate cancer, bone cancer, head and neck cancer, skin cancer, thyroid cancer, parathyroid cancer, ureteral cancer, and blood cancer. 10.1) ACPP, ADA, ALK, BCR-ABL-1, BTK, CDK4, CDK6, CD19, CD3D, CD52, C-MET, CRBN, CTLA4, CYP17A1, DDR2, ERBB4, FCGR1A, FGF1, FGFR1, FGFR2, FGFR3, FRK, GNRH1, GNRHR, HDAC2, HDAC3, HPRT1, IFNAR1, IFNAR2, IL2RA, IL2RB, IL2RG, ITK, JAK1, JAK2, LDLR, LHCGR, LIMK1, MAP1A, MAP2, MAP2K1, MAP2K2, MAPK11, NEK11, NR3C1, NTRK1, PARP1, PARP2, PARP3, PDCD1, PGF, A step of measuring the expression of at least two target genes selected from the group consisting of PIK3CD, PRLR, PSMB10, PSMB1, PSMB2, PSMB8, PSMB9, PSMD1, PSMD2, PTK6, RARA, RARB, RARG, RPL3, SH2B3, SIK1, SLC2A2, SMO, SSTR2, SSTR5, TEK, TLR8, TNFSF8, TNFSF11, TOP1MT, TOP2B, TUBA1A, TUBA4A, TUBB1, TUBB3, TUBB, TUBD1, TUBE1, TUBG1, VEGFA and VEGFB; and 2) A method for screening a drug tailored to a cancer patient, comprising a step of screening a drug that acts on a target gene measured to be highly expressed in step 1).

11. A method for screening a cancer patient for a personalized medicine, characterized in that in clause 10, the measurement of the expression of the gene is performed according to a quantitative real-time PCR method. 12.1) A step of isolating and proliferating cancer cells and normal cells from cancer tissue and normal tissue isolated from a cancer patient; 2) a step of treating the cancer cells of step 1) with a cancer treatment candidate drug; 3) A step of isolating total RNA from the cancer cells and normal cells of step 1) and the cancer cells treated with the cancer treatment candidate drug of step 2), and synthesizing cDNA using the total RNA as a template; 4) Using the cDNA synthesized in the above step 3) as a template, ACPP, ADA, ALK, BCR-ABL-1, BTK, CDK4, CDK6, CD19, CD3D, CD52, C-MET, CRBN, CTLA4, CYP17A1, DDR2, ERBB4, FCGR1A, FGF1, FGFR1, FGFR2, FGFR3, FRK, GNRH1, GNRHR, HDAC2, HDAC3, HPRT1, IFNAR1, IFNAR2, IL2RA, IL2RB, IL2RG, ITK, JAK1, JAK2, LDLR, LHCGR, LIMK1, MAP1A, MAP2, MAP2K1, MAP2K2, MAPK11, NEK11, NR3C1, NTRK1, PARP1, PARP2, PARP3, PDCD1, A step of amplifying a target gene using primers or probes that specifically hybridize to at least two target genes each selected from the group consisting of PGF, PIK3CD, PRLR, PSMB10, PSMB1, PSMB2, PSMB8, PSMB9, PSMD1, PSMD2, PTK6, RARA, RARB, RARG, RPL3, SH2B3, SIK1, SLC2A2, SMO, SSTR2, SSTR5, TEK, TLR8, TNFSF8, TNFSF11, TOP1MT, TOP2B, TUBA1A, TUBA4A, TUBB1, TUBB3, TUBB, TUBD1, TUBE1, TUBG1, VEGFA and VEGFB; and 5) A method for screening a personalized medicine for a cancer patient, comprising a step of measuring the expression amount of the amplified target gene in step 4) and then comparing the expression amount of the target gene in normal cells, cancer cells, and cancer cells treated with a cancer treatment candidate drug.

13. A method for screening a personalized medicine for a cancer patient, characterized in that the primer or probe in claim 12 is a primer or probe for quantitative real-time PCR.

14. A method for screening a personalized medicine for a cancer patient, characterized in that in the 12th paragraph, a candidate drug is selected in which the expression amount of the target gene amplified in step 5) increases in cancer cells compared to normal cells, and decreases in cancer cells treated with the candidate cancer treatment drug compared to cancer cells.

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