Biomarker for measuring anticancer drug resistance and method of providing anticancer drug resistance prediction information using the same

Abstract

The present invention relates to a biomarker for measuring anticancer drug resistance comprising a gene expressed in a group of cancer cells, wherein the gene releases an anticancer drug that has penetrated into the group of cancer cells to the outside of the group of cancer cells, wherein the gene comprises a gene selected from the group consisting of ABCG1, p-STAT3, STAT3, p-AKT, AKT, p-ERK, ERK, β-actin, ACTA2, GAS6, FAP, PDPN, COL1A1, AXL, and combinations thereof.

Description

Technology Field

[0001] The present invention relates to a biomarker for measuring anticancer drug resistance and a method for providing information on predicting anticancer drug resistance using the same. Background Technology

[0003] Patients with stage 4 gastric cancer, in which the tumor has already progressed and is unresectable, receive chemotherapy such as 5-Fluorouracil (5-FU) and Cisplatin, but there is a problem where the effectiveness is reduced due to drug resistance. Recently, the existence and roles of immune cells, vascular cells, and cancer-associated fibroblasts surrounding cancer cells, as well as cancer cells, have been identified as causes for this reduction in drug efficacy. Among these, there are reports that cytokines or chemokines secreted by cancer-associated fibroblasts are associated with increased drug resistance and poor prognosis in gastric cancer.

[0004] In other words, cytokines or chemokines can function as biomarkers capable of measuring drug resistance. Generally, a biomarker refers to an indicator that can detect changes within the body using proteins, DNA, RNA, metabolites, etc. For example, through genes expressed in a population of cancer cells, it is possible to determine whether the cancer cells are disappearing, proliferating, or interacting with anticancer drugs; in this case, the expressed genes can be referred to as biomarkers.

[0005] Meanwhile, gastric cancer ranks fifth in incidence and fourth in mortality among the most common cancers worldwide, yet it is known that chemotherapy and targeted therapy techniques have not significantly improved the survival rate of patients with advanced gastric cancer. This is because treatment has focused solely on cancer cells and the impact of cancer-associated fibroblasts on cancer treatment has not been recognized; however, research analyzing the impact of cancer-associated fibroblasts on cancer treatment is currently being conducted.

[0006] Korean Registered Patent Publication No. 10-0839585, which is the background technology of the present invention, relates to a method for detecting anticancer drug resistance genes using multiplex PCR and a detection kit using the same. The problem to be solved

[0008] The present invention aims to solve the problems of the aforementioned prior art by providing a biomarker for measuring anticancer drug resistance and an anticancer drug resistance measurement kit containing the same.

[0009] In addition, the present invention aims to provide a composition for preventing anticancer drug resistance using the above-mentioned biomarker for measuring anticancer drug resistance.

[0010] In addition, the present invention aims to provide a method for providing information to predict resistance to anticancer drug treatment using the aforementioned biomarker for measuring anticancer drug resistance.

[0011] However, the technical problems that the embodiments of the present invention aim to solve are not limited to the technical problems described above, and other technical problems may exist. means of solving the problem

[0012] As a technical means for achieving the above-mentioned technical problem, the first aspect of the present invention relates to a biomarker for measuring anticancer drug resistance, comprising a gene expressed in a group of cancer cells, wherein the gene releases an anticancer drug that has penetrated into the group of cancer cells to the outside of the group of cancer cells, wherein the gene comprises a gene selected from the group consisting of ABCG1, p-STAT3, STAT3, p-AKT, AKT, p-ERK, ERK, β-actin, ACTA2, GAS6, FAP, PDPN, COL1A1, AXL, and combinations thereof.

[0013] According to one embodiment of the present invention, the gene may include ABCG1, but is not limited thereto.

[0014] According to one embodiment of the present invention, the cancer cell group may include cancer cells and cancer-associated fibroblasts (CAFs) formed around the cancer cells, but is not limited thereto.

[0015] According to one embodiment of the present invention, the expression level of the gene may be proportional to the degree of culture of the cancer cell group, but is not limited thereto.

[0016] In addition, a second aspect of the present invention relates to a kit for measuring anticancer drug resistance, comprising a biomarker for measuring anticancer drug resistance according to the first aspect.

[0017] In addition, a third aspect of the present invention relates to a composition for preventing anticancer drug resistance comprising a STAT3 inhibitor, wherein the expression of a gene expressed in a group of cancer cells is suppressed by said STAT3 inhibitor.

[0018] According to one embodiment of the present invention, the composition for preventing anticancer drug resistance may additionally include a gene inhibitor selected from the group consisting of AXL inhibitors, EKR 1 inhibitors, EKR 2 inhibitors, AKT inhibitors, NF-kB inhibitors, and combinations thereof, but is not limited thereto.

[0019] According to one embodiment of the present invention, the gene may include, but is not limited to, one selected from the group consisting of ABCG1, p-STAT3, STAT3, p-AKT, AKT, p-ERK, ERK, β-actin, ACTA2, GAS6, FAP, PDPN, COL1A1, AXL, and combinations thereof.

[0020] According to one embodiment of the present invention, the gene may include ABCG1, but is not limited thereto.

[0021] According to one embodiment of the present invention, the cancer cell group may include cancer cells and cancer-associated fibroblasts (CAFs) formed around the cancer cells, but is not limited thereto.

[0022] In addition, a fourth aspect of the present invention relates to a method for providing information for predicting resistance to anticancer drug treatment, comprising the steps of: measuring a gene expressed in a group of cancer cells; measuring the resistance to an anticancer drug in said group of cancer cells; and analyzing the correlation between the degree of expression of said measured gene and said measured resistance to the anticancer drug.

[0023] According to one embodiment of the present invention, the method may further include, but is not limited to, the step of administering a gene inhibitor to a group of cancer cells; the step of measuring a gene expressed in the group of cancer cells administered the gene inhibitor; the step of measuring the anticancer drug resistance of the group of cancer cells administered the gene inhibitor; and the step of analyzing the correlation between the degree of expression of the measured gene and the measured anticancer drug resistance.

[0024] According to one embodiment of the present invention, the correlation between the measured degree of gene expression and the measured anticancer drug resistance may have a positive correlation, but is not limited thereto.

[0025] The means for solving the problem described above are merely exemplary and should not be interpreted as intended to limit the present invention. In addition to the exemplary embodiments described above, additional embodiments may exist in the drawings and the detailed description of the invention. Effects of the invention

[0026] During the conventional treatment of hepatocellular carcinoma (HCC), it was confirmed that the expression of ABCG1 increased upon treatment with Src tyrosine kinase inhibitors (TKIs) and the chemotherapy drug oxaliplatin, which was confirmed by RNA sequencing as the Wnt signaling pathway was activated. At this time, genetically knocking down ABCG1 expression significantly reduced tumor size in a mouse in vivo model, but the mechanism by which the Wnt signaling pathway increases ABCG1 expression is unknown.

[0027] In addition, resistance to the chemotherapy drug cisplatin has been confirmed in lung adenocarcinoma, and it has been confirmed that this is because HOXB13 directly binds to the ABCG1 promoter and is involved in cancer metastasis and drug resistance; however, no studies have been conducted to identify the cause of the increase in HOXB13 upon cisplatin treatment, the signaling pathway, and what phenomena occur in a mouse model by controlling the expression of ABCG1.

[0028] In addition, it has been confirmed that resistance to 5-fluorouracil and oxaliplatin develops in colorectal cancer (CRC), and it is known that ABCG1, an ATP transporter, increases the role of effluxing drugs out of the cell via the Hedgehog-GLI signaling pathway and that GLI transcription factors regulate ABC transporters transcriptionally; however, no studies have been conducted to confirm what happens in a mouse in vivo model by controlling the expression of ABCG1.

[0029] However, the researchers of the present invention confirmed through proteomic analysis that ABCG1 is increased in cancer-associated fibroblasts and co-cultured cancer cells, and identified this as a novel resistance mechanism that causes anticancer drug resistance that was previously unknown. Through this, a method to suppress anticancer drug resistance can be proposed using the biomarker for measuring anticancer drug resistance according to the present invention.

[0030] In addition, by measuring the expression of the biomarker for measuring anticancer drug resistance, resistance to anticancer drug treatment can be predicted, and thereby the anticancer drug to be administered to the patient can be adjusted.

[0031] However, the effects obtainable from this invention are not limited to those described above, and other effects may exist. Brief explanation of the drawing

[0033] FIG. 1 is a schematic diagram showing the mechanism of action of a gene according to one embodiment of the present invention. Figure 2 is the result of immunochemical staining of a group of cancer cells according to one embodiment of the present invention. Figure 3 is the result of immunochemical staining of a group of cancer cells according to one embodiment of the present invention. Figure 4 is a result showing the degree of inhibition of gene expression according to one embodiment of the present invention. FIGS. 5A and 5B show the cell viability of a cancer cell group according to one embodiment of the present invention. Figures 6a and 6b show RT-PCR of a cancer cell group according to one embodiment of the present invention. FIGS. 7a and 7b show the cell viability of a cancer cell group according to one embodiment of the present invention. FIGS. 8a and 8b compare the expression between cancer-related fibroblast markers and genes according to one embodiment of the present invention. FIGS. 9a and 9b compare the expression between cancer-related fibroblast markers and genes according to one embodiment of the present invention. FIG. 10 is an image confirming gene expression within a group of cancer cells according to one embodiment of the present invention. Specific details for implementing the invention

[0034] Below, embodiments of the present invention are described in detail with reference to the attached drawings so that those skilled in the art can easily implement them.

[0035] However, the present invention may be implemented in various different forms and is not limited to the embodiments described herein. Furthermore, in order to clearly illustrate the present invention in the drawings, parts unrelated to the description have been omitted, and similar parts throughout the specification have been given similar reference numerals.

[0036] Throughout this specification, when a part is described as being "connected" to another part, this includes not only cases where they are "directly connected," but also cases where they are "electrically connected" with other elements interposed between them.

[0037] Throughout the entire specification, when a component is described as being located "on," "on top," "on top," "under," "on bottom," or "on bottom" of another component, this includes not only cases where the component is in contact with the other component but also cases where another component exists between the two components.

[0038] Throughout this specification, when a part is described as "comprising" a certain component, this means that, unless specifically stated otherwise, it does not exclude other components but may include additional components.

[0039] As used herein, terms of degree such as “about,” “substantially,” etc., are used to mean at or near the stated value when inherent manufacturing and material tolerances are presented in the stated meaning, and are used to prevent unscrupulous infringers from unfairly exploiting the disclosure in which precise or absolute values ​​are mentioned to aid in understanding the present invention. Furthermore, throughout this specification, “a step of” or “a step of” does not mean “a step for”.

[0040] Throughout this specification, the term “combination thereof” included in the Markush-type expression means one or more mixtures or combinations selected from the group consisting of the components described in the Markush-type expression, and means including one or more selected from the group consisting of said components.

[0041] Throughout the entire specification, the description "A and / or B" means "A or B, or, A and B".

[0042] Hereinafter, the biomarker for measuring anticancer drug resistance and the method for providing anticancer drug resistance prediction information using the same according to the present invention will be described in detail with reference to embodiments, examples, and drawings. However, the present invention is not limited to these embodiments, examples, and drawings.

[0043] As a technical means for achieving the above-mentioned technical problem, the first aspect of the present invention relates to a biomarker for measuring anticancer drug resistance, comprising a gene expressed in a group of cancer cells, wherein the gene releases an anticancer drug that has penetrated into the group of cancer cells to the outside of the group of cancer cells, wherein the gene comprises a gene selected from the group consisting of ABCG1, p-STAT3, STAT3, p-AKT, AKT, p-ERK, ERK, β-actin, ACTA2, GAS6, FAP, PDPN, COL1A1, AXL, and combinations thereof.

[0044] A biomarker according to the present invention refers to an indicator that can detect changes within the body using proteins, DNA, RNA, metabolites, etc. That is, through genes expressed in the cancer cell population, it is possible to determine whether the cancer cell population is disappearing, proliferating, or interacting with anticancer drugs, and such genes can be referred to as biomarkers.

[0045] According to one embodiment of the present invention, the gene may include ABCG1, but is not limited thereto.

[0046] According to one embodiment of the present invention, the cancer cell group may include cancer cells and cancer-associated fibroblasts (CAFs) formed around the cancer cells, but is not limited thereto.

[0047] According to one embodiment of the present invention, the expression level of the gene may be proportional to the degree of culture of the cancer cell group, but is not limited thereto.

[0048] ABCG1 according to the present invention was known to be expressed in cancer cells. However, when cancer-associated fibroblasts were taken from a group of cancer cells and cultured, and the expression of ABCG1 was measured, it was confirmed that ABCG1 was also expressed in the cancer-associated fibroblasts.

[0049] According to one embodiment of the present invention, the gene can release an anticancer agent that has infiltrated into the cancer cell group to the outside of the cancer cell group, but is not limited thereto.

[0050] FIG. 1 is a schematic diagram showing the mechanism of action of a gene according to one embodiment of the present invention.

[0051] Generally, chemotherapy used to eliminate cancer cell populations can do so by acting directly on DNA after the anticancer drug has penetrated the cell population, thereby blocking DNA replication, transcription, and translation processes, interfering with the synthesis of nucleic acid precursors in metabolic pathways, and inhibiting cell division. However, it was observed that in some cancer patients, the degree of cancer cell elimination was low even after the administration of a standard dose of anticancer drug; investigation revealed that this was because the aforementioned gene facilitated the expulsion of the anticancer drug that had penetrated the cancer cell population to the outside.

[0052] Referring to Figure 1, the anticancer agent Rhodamine 123 located inside the cancer cell group can be expelled to the outside of the cancer cell group through a channel formed by ABCG1.

[0053] As will be described later, the increase in expression of the above-mentioned gene ABCG1 can be suppressed through AXL and STAT3 transcription factor inhibitors corresponding to the upstream regulatory pathway.

[0054] In addition, a second aspect of the present invention relates to a kit for measuring anticancer drug resistance, comprising a biomarker for measuring anticancer drug resistance according to the first aspect.

[0055] As described above, the biomarker for measuring anticancer drug resistance includes a gene that expels the anticancer drug that has infiltrated the cancer cell population to the outside. In other words, the degree of resistance to the anticancer drug can be measured by measuring the expression level of the said gene.

[0056] In addition, a third aspect of the present invention relates to a composition for preventing anticancer drug resistance comprising a STAT3 inhibitor, wherein the expression of a gene expressed in a group of cancer cells is suppressed by said STAT3 inhibitor.

[0057] In this regard, the above composition for preventing anticancer drug resistance is intended to suppress the expression of a biomarker for measuring anticancer drug resistance according to the first aspect of the present invention, and when the expression of the biomarker is suppressed, the expression of the gene in the cancer cell population is suppressed, thereby reducing the resistance of the cancer cell population to the anticancer drug.

[0058] According to one embodiment of the present invention, the composition for preventing anticancer drug resistance may additionally include a gene inhibitor selected from the group consisting of AXL inhibitors, EKR 1 inhibitors, EKR 2 inhibitors, AKT inhibitors, NF-kB inhibitors, and combinations thereof, but is not limited thereto.

[0059] According to one embodiment of the present invention, the gene may include, but is not limited to, one selected from the group consisting of ABCG1, p-STAT3, STAT3, p-AKT, AKT, p-ERK, ERK, β-actin, ACTA2, GAS6, FAP, PDPN, COL1A1, AXL, and combinations thereof.

[0060] According to one embodiment of the present invention, the gene may include ABCG1, but is not limited thereto.

[0061] The expression of the above gene can be inhibited through AXL and STAT3 transcription factor inhibitors corresponding to the upstream regulatory pathway. Specifically, the expression of the above gene can be regulated by inhibiting the activation of AXL and STAT3, which control the expression level of ABCG1.

[0062] According to one embodiment of the present invention, the cancer cell group may include cancer cells and cancer-associated fibroblasts (CAFs) formed around the cancer cells, but is not limited thereto.

[0063] Cancer-associated fibroblasts according to the present invention are fibroblasts that promote tumor initiation, growth, and progression through signals that promote the proliferation, angiogenesis, and inflammation of cancer cells, and it was confirmed that genes that impair the performance of the anticancer agent are expressed not only in cancer cells but also in cancer-associated fibroblasts.

[0064] In this regard, it was confirmed that the aforementioned gene, specifically the gene that releases anticancer drugs from within the cancer cell population to the outside, is expressed not only in cancer cells but also in cancer-associated fibroblasts.

[0065] In addition, a fourth aspect of the present invention relates to a method for providing information for predicting resistance to anticancer drug treatment, comprising the steps of: measuring a gene expressed in a group of cancer cells; measuring the resistance to an anticancer drug in said group of cancer cells; and analyzing the correlation between the degree of expression of said measured gene and said measured resistance to the anticancer drug.

[0066] In this regard, the gene expressed in the above-mentioned cancer cell group refers to a biomarker according to the first aspect of the present invention. In this case, the biomarker includes a gene that releases an anticancer drug from within the cancer cell group to the outside, and the higher the expression level of said gene, the more the said anticancer drug is released to the outside, which means that said cancer cell group has high resistance to the anticancer drug.

[0067] According to one embodiment of the present invention, the method may further include, but is not limited to, the step of administering a gene inhibitor to a group of cancer cells; the step of measuring a gene expressed in the group of cancer cells administered the gene inhibitor; the step of measuring the anticancer drug resistance of the group of cancer cells administered the gene inhibitor; and the step of analyzing the correlation between the degree of expression of the measured gene and the measured anticancer drug resistance.

[0068] The expression levels of genes expressed in the above-mentioned cancer cell group and the measured values ​​of anticancer drug resistance in the above-mentioned cancer cell group may have a positive correlation. In this case, after administering a gene inhibitor to the above-mentioned cancer cell group, when the expression levels of genes expressed in the above-mentioned cancer cell group and the measured values ​​of anticancer drug resistance in the above-mentioned cancer cell group are compared with the values ​​of a cancer cell group that was not previously administered the gene inhibitor, it can be confirmed that the gene expression levels decreased in the group administered the gene inhibitor, and consequently, anticancer drug resistance also decreased.

[0069] The above gene inhibitor is intended to inhibit the expression of the gene of the above biomarker and preferably includes a STAT3 inhibitor, and may additionally include an AXL inhibitor, but is not limited thereto.

[0070] According to one embodiment of the present invention, the correlation between the measured degree of gene expression and the measured anticancer drug resistance may have a positive correlation, but is not limited thereto.

[0071] Specifically, when analyzing the publicly available data of GSE62254 and GSE84437, it was confirmed that the expression of ABCG1 in gastric cancer patients had a positive correlation with cancer-associated fibroblast markers, and when the expression of ABCG1 and cancer-associated fibroblasts was high, the prognosis of gastric cancer was poor. However, the expression level of ABCG1 can be controlled by AXL and STAT3 transcription factor inhibitors, which correspond to the upstream regulatory pathways that regulate the action of ABCG1.

[0072] The means for solving the problem described above are merely exemplary and should not be interpreted as intended to limit the present invention. In addition to the exemplary embodiments described above, additional embodiments may exist in the drawings and the detailed description of the invention.

[0073] The present invention is to be explained in more detail through the following examples, but the following examples are for illustrative purposes only and are not intended to limit the scope of the present invention.

[0074] [Example]

[0075] The expression of genes such as ABCG1 was investigated using cancer cells (SNU668, MKN1, GSE62254, GSE84437).

[0076] [Experimental Example 1]

[0077] Figures 2 and 3 are the results of immunohistochemical staining of a group of cancer cells according to one embodiment of the present invention. In this regard, the arrow in Figure 2 indicates the expression of ABCG1, and since ABCG1 is mainly expressed in the cell membrane, the arrow indicates the part where the expression of ABCG1 is prominent.

[0078] Referring to Figures 2 and 3, it can be confirmed that the color development of DAPI and the color development point of ABCG1 coincide.

[0079] [Experimental Example 2]

[0080] FIG. 4 is a result showing the degree of inhibition of gene expression according to one embodiment of the present invention, FIG. 5a, FIG. 5b, FIG. 7a, and FIG. 7b show the cell viability of a cancer cell group according to one embodiment of the present invention, and FIG. 6a and FIG. 6b show the RT-PCR of a cancer cell group according to one embodiment of the present invention.

[0081] Referring to Figures 4 to 7b, it can be seen that the expression of ABCG1 is inhibited by STAT3.

[0082] Specifically, referring to Figure 4, when the gastric cancer cell line SNU668 is co-cultured with CAF, activation of known downstream signaling pathways for AXL occurs in the gastric cancer cell line, which is the result of treating the gastric cancer cell line with inhibitors corresponding to ERK, AKT, STAT3, and NF-kB, respectively. As a result, it means that when the gastric cancer cell line is treated with a STAT3 inhibitor, the expression of ABCG1 can be inhibited in a concentration-dependent manner.

[0083] In addition, referring to Figure 5b, when gastric cancer cell lines and CAF are co-cultured, an increase in the protein and gene levels of ABCG1 can be observed, and even in a normal state without co-culture with CAF, it can be confirmed that ABCG1 performs the anticancer drug efflux function.

[0084] In addition, referring to Figure 7b, it can be confirmed that when gastric cancer cell lines are treated with CAF-CM (CAF conditioned medium) under conditions where the anticancer drug 5-FU is treated, anticancer drug resistance develops and cancer cell survival increases, but when the ABCG1 gene in gastric cancer cell lines is knocked down, anticancer drug resistance can be suppressed.

[0085] [Experimental Example 3]

[0086] FIGS. 8a, FIGS. 8b, FIGS. 9a, and FIGS. 9b compare the expression between cancer-related fibroblast markers and genes according to one embodiment of the present invention. In this case, the table at the bottom of the graph in FIGS. 9a and 9b represents the ABCG1 / ACTA2+ group (top left), ABCG1 / PDPN+ group (top right), ABCG1 / FAP+ group (bottom left), ABCG1 / COL1A1 group (bottom right), and other groups (blue graphs for each graph).

[0087] Referring to Figures 8a to 9b, it can be seen that the expression of ABCG1 in GSE62254 and GSE64437 has a positive correlation with the expression of PDPN and AXL in common.

[0088] In this regard, PDPN is a genetic marker of CAF, and inhibiting the GAS6 protein, which can activate AXL in gastric cancer cell lines, can regulate ABCG1 expression in gastric cancer cell lines rather than inhibiting PDPN in CAF.

[0089] [Experimental Example 4]

[0090] Figure 10 is an image confirming gene expression within a group of cancer cells according to one embodiment of the present invention. In this regard, Figure 10 is an immunohistochemical staining of gastric cancer tissue from a patient who underwent gastric cancer resection surgery, and the red arrow in Figure 10 indicates the expression of ABCG1 in the cancer cell line.

[0091] Referring to Figure 10, the expression of ABCG1 can be confirmed even after gastric cancer cells have been resected, which means that ABCG1 is expressed not only in gastric cancer cells but also in gastric cancer CAFs surrounding gastric cancer cells.

[0092] The foregoing description of the present invention is for illustrative purposes only, and those skilled in the art will understand that other specific forms can be easily modified without altering the technical concept or essential features of the present invention. Therefore, the embodiments described above should be understood as illustrative in all respects and not restrictive. For example, each component described as a single unit may be implemented in a distributed manner, and components described as distributed may likewise be implemented in a combined form.

[0093] The scope of the present invention is defined by the claims set forth below rather than by the detailed description above, and all modifications or variations derived from the meaning and scope of the claims and the concept of equivalents thereof should be interpreted as being included within the scope of the present invention.

Claims

Claim 1 A biomarker for measuring anticancer drug resistance comprising a gene expressed in a group of cancer cells, wherein the group of cancer cells comprises gastric cancer cells and cancer-associated fibroblasts (CAFs) formed around the gastric cancer cells, and wherein an anticancer drug that has infiltrated into the group of cancer cells by the gene expressed in the gastric cancer cells or the gene expressed in the CAFs is expelled to the outside of the group of cancer cells, wherein the gene expressed in the gastric cancer cells comprises a gene selected from the group consisting of ABCG1, p-STAT3, STAT3, AXL, and combinations thereof, and the gene expressed in the CAFs comprises a gene selected from the group consisting of GAS6, ACTA2, FAP, PDPN, COL1A1, and combinations thereof, and wherein the anticancer drug is a chemotherapy anticancer drug. Claim 2 delete Claim 3 delete Claim 4 A biomarker for measuring anticancer drug resistance according to claim 1, wherein the expression level of the gene is proportional to the degree of culture of the cancer cell group. Claim 5 An anticancer drug resistance measurement kit comprising a biomarker for measuring anticancer drug resistance according to either claim 1 or claim 4. Claim 6 delete Claim 7 delete Claim 8 delete Claim 9 delete Claim 10 delete Claim 11 A step of measuring the expression level of a biomarker for measuring anticancer drug resistance according to claim 1 expressed in a group of cancer cells isolated from the human body; a step of measuring the anticancer drug resistance of the cancer cell group; A method for providing information for predicting resistance to anticancer drug treatment, comprising the step of analyzing the correlation between the expression level of the measured biomarker and the measured anticancer drug resistance, wherein the cancer cell group comprises gastric cancer cells and cancer-associated fibroblasts (CAFs) formed around the gastric cancer cells, the biomarker comprises a gene expressed in the cancer cell group, and an anticancer drug that has penetrated into the cancer cell group by the gene expressed in the gastric cancer cells or the gene expressed in the CAF is expelled to the outside of the cancer cell group, the gene expressed in the gastric cancer cells comprises a gene selected from the group consisting of ABCG1, p-STAT3, STAT3, AXL, and combinations thereof, and the gene expressed in the CAF comprises a gene selected from the group consisting of GAS6, ACTA2, FAP, PDPN, COL1A1, and combinations thereof, and the anticancer drug comprises a chemotherapy anticancer drug. Claim 12 A method for providing information for predicting resistance to anticancer drug treatment, wherein, in claim 11, the step of administering a gene inhibitor onto a group of cancer cells; the step of measuring the expression level of a biomarker for measuring anticancer drug resistance expressed in the group of cancer cells administered the gene inhibitor; the step of measuring the anticancer drug resistance of the group of cancer cells administered the gene inhibitor; and the step of analyzing the correlation between the expression level of the biomarker for measuring anticancer drug resistance measured above and the measured anticancer drug resistance. Claim 13 A method for providing information for predicting resistance to anticancer drug treatment, wherein, in claim 11, the correlation between the expression level of the biomarker for measuring anticancer drug resistance measured above and the measured anticancer drug resistance has a positive correlation.

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