Drug Screening Of CLDN18-ARHGAP26 Fusion Gene And Identification Of Key Gene COL4A1 In Gastric Cancer

Globally,gastric cancer is one of the most common and deadly malignant tumors.In recent years,the treatment of gastric cancer has become increasingly perfect and diversified.However,the 5-year survival rate of gastric cancer patients is still low.The most important reason for the high mortality rate of gastric cancer patients is that the early diagnosis rate of gastric cancer patients is low,and most patients are in the late stage when they are diagnosed.Currently,chemotherapy is the primary treatment for the middle and advanced stages of the disease.Still,treatment failure is often reported due to chemotherapy resistance,and the rapid development of precision treatment mode brings new hope for the treatment of gastric cancer patients.Drugs acting on specific targets can help precise treatment of clinical patients and improve the therapeutic effect while identifying new biomarkers that can be used for early diagnosis and correct management of patients,providing the clinical basis for early diagnosis and late precision treatment of gastric cancer patients.This paper mainly includes the following contents:The CLDN18-ARHGAP26 fusion gene was significantly overexpressed in patients with diffuse gastric cancer through whole-genome sequencing.The CLDN18-ARHGAP26 fusion gene was speculated could be a specific potential therapeutic target.Therefore,we envisaged searching for drugs targeting the CLDN18-ARHGAP26 fusion gene and screening the FDAapproved drug library to find Usnic acid-sensitive to gastric cancer cells overexpressing the CLDN18-ARHGAP26 fusion gene.Further research found that the drug mainly inhibits the migration ability of cells,induces apoptosis of cells,and accelerates cell death.Gastric cancer cells overexpressing the CLDN18-ARHGAP26 fusion gene are not sensitive to chemotherapeutic drugs.However,we found that the cells combined the chemotherapeutic drug 5-FU with Usnic acid.This chapter provides a theoretical basis and guidance for individualized clinical medicine for gastric cancer patients with high expression of the CLDN18-ARHGAP26 gene.In addition to seeking better treatment for gastric cancer patients,early diagnosis is also crucial.There is still a lack of effective methods for the early diagnosis of gastric cancer.Still,it is more important to improve the diagnosis of gastric cancer patients by identifying valuable predictive biomarkers.We used bioinformatics technology to find critical genes in gastric cancer.Firstly,this study used the public datasets TCGA-STAD,GSE13861,and GSE29272 to overlap with the secretome gene data and screened out 25 differentially expressed genes.Secondly,six candidate genes highly expressed in gastric cancer patients were identified using LASSO logistic regression: OLFM4,CEMIP,APOC1,CST1,COL4A1,and CD55.Using TCGA-STAD,GSE62254,and GSE84437 as the validation set,through univariate COX regression and Kaplan-Meier survival analysis,we found that COL4A1 was significantly correlated with the poor prognosis of gastric cancer patients,which may be a gastric cancer-specific marker.The biological role of COL4A1 was determined by pathway analysis of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG).GO study showed that COL4A1 is mainly involved in biological processes such as connective tissue development,collagen fiber organization-related processes,extracellular structure organization,and extracellular matrix organization,which play a significant role in connecting and maintaining cell morphology.KEGG analysis found several biological pathways of interest,such as extracellular matrix(ECM)receptor-related pathways,focal adhesion,PI3K-Akt signaling pathway,Etc.,which are involved in cell proliferation and migration and are closely related to the occurrence and development of cancer.Furthermore,immunohistochemical(IHC)analysis on tissue chips further verified that the protein expression level of COL4A1 in gastric cancer tissues was significantly higher than that in adjacent tissues.Our study shows that COL4A1 may be a new diagnostic and prognostic marker for gastric cancer patients and provides unique research ideas and directions for the study of gastric cancer.