Genetic Alterations And Expression Characteristics Of ARID1A Impact Tumor Immune Contexture And Survival In Early-onset Gastric Cancer

Objective: AT-rich domain 1A(ARID1A)is one of the most important subunits of chromatin remodeling complex SWI/SNF,and it is also one of the most frequently mutated genes in gastric cancer.However,there are few studies on the ARID1 A gene in the initial stage of tumorigenesis.There are few young gastric cancer cases(≤40 years old,EOGC)in most databases including TCGA.There is an urgent need to systematically explore the genetic alterations and protein expression of ARID1 A in this unique clinical model of early-onset gastric cancer to reveal the unknown role of ARID1 A.Methods: Deep-targeted high-throughput sequencing technology was used to reveal the precise mutation spectrum of ARID1 A in early-onset gastric cancer.Immunohistochemical staining was used to show the protein levels of ARID1 A in EOGC patients.Multiplex immunohistochemical staining technology was used to demonstrate in depth the potential dynamic effects of ARID1 A protein expression on tumor-infiltrating T cell subsets in the tumor immune microenvironment.16 S r RNA gene sequencing technology was conducted to explore the composition of the intratumor microbiome of EOGC patients and its impact on the prognosis.Results: Comparing the results of targeted sequencing with the existing mutation data archived in databases such as TCGA,Ex Ac,1000 Genomes,and Clin Var revealed a large number of unreported coding mutations and noncoding mutations in the EOGC patients.ARID1 A protein expression was significantly reduced in non-coding mutation EOGC patients.Studies have found that cases with genetic variation of ARID1 A,lower expression of ARID1 A protein,and lower heterogeneous expression have better survival benefits.Multispectral imaging technology revealed that the protein expression and heterogeneous expression of ARID1 A significantly affect the density and spatial distribution of TIL in tumors,and even have a certain impact on the function of cytotoxic T lymphocytes.The tumor microbiota analysis revealed that microbial diversity is related to the poor prognosis of EOGC patients,and there are significant differences in tumor microbiota between favorable prognosis group and unfavorable prognosis group.Conclusion: In short,our results indicate that the genetic variation and protein changes of ARID1 A gene have occurred in the initial stage of tumorigenesis,which will affect future survival benefits.ARID1 A may have an important molecular influence on the formation of tumor immune environment during the initial stage of tumor development.Compared with traditional methods of evaluating tumor ARID1 A expression levels,simultaneously evaluating ARID1 A expression patterns(overall level and heterogeneous expression)in tumor and paratumor tissues may be a potential new strategy for better predicting the molecular impact of ARID1 A protein changes,and more precise stratification of patients before targeted therapy and immunotherapy.