Pan-cancer Analysis Of MS4A15 And Verification Of Its Role In Lung Adenocarcinoma Cell

BackgroundMS4A15 belongs to transmembrane proteins and has been recognized as a regulator of various biological events.Existing evidence demonstrates its role in the tumorigenesis of ovarian cancer.However,there still lacks a systematic and comprehensive pan-cancer analysis of the role of MS4A15 in the occurrence and development,prognosis and immunology of other tumors.In this study,we analyzed MS4A15 and explored its possible role in pan-cancer,and verified its functional role in LUAD.MethodsWe explored and validated the mRNA and protein expression levels of MS4A15 in pan-cancer through public databases.The Kaplan-Meier analysis and Univariate/multivariate Cox regression analysis were applied to assess the prognostic value of MS4A15.The correlation between MS4A15 expression and clinical characteristics and immunological features in diverse tumors was also explored.The co-expression genes of MS4A15 were used for GO/KEGG analysis,and GSEA enriched biological functions and participating signal pathways.Additionally,the lung adenocarcinoma cell which was expressed MS4A15 was constructed by lentivirus,and the biological function of MS4A15 in vitro was verified by CCK-8 test,clone formation assay,cell scratch test and transwell.ResultsIn ACC,BLCA,CESC,KIRC and UCEC,the expression of MS4A15 is higher than that in corresponding normal tissues;the high expression of MS4A15 will cause poor survival(progression-free interval/overall survival);the expression of MS4A15 is higher in tumors with later stage,and it is negatively correlated with immune infiltration;MS4A15 may inhibit B cell,dendritic cell and other immune cell infiltration by positively regulating lipid metabolism participated in by EBP,HSD17B7 and LHB,positively regulating monoatomic ion transmembrane transport,potassium ion transmembrane plasma channel,transmembrane transport pathway,or directly inhibiting immune-related pathways such as MHC,CTL,IL-17,etc.In READ,the expression of MS4A15 is higher than that in normal tissues,and the high expression of MS4A15 suggests better overall survival.In UCS,the expression of MS4A15 is higher than that in normal tissues and the high expression of MS4A15 suggests better progression-free interval In BRCA,COAD,ESCA,GBM,HNSC,LIHC,OV,PAAD,PRAD,SKCM,STAD,THCA,THYM,DLBC,the expression of MS4A15 is higher than that in corresponding normal tissues,while in LUSC,LGG,PCPG,TGCT,LAML,the expression of MS4A15 is lower than that in corresponding normal tissues,there is no significant correlation between its expression and survival.In CHOL,KICH,KIRP,MESO,SARC,UVM,there is no significant difference in the expression of MS4A15 between tumor and corresponding normal tissues,and there is no significant correlation between the expression and survival.In LUAD,the expression of MS4A15 is lower than that in corresponding normal tissues;the low expression of MS4A15 is associated with poor survival(progression-free interval/overall survival);the expression of MS4A15 is lower in tumors with later stage,and it is positively correlated with immune infiltration;the expression of MS4A15 is negatively correlated with later tumor stage and lower immune infiltration;MS4A15 may promote the infiltration of immune cells such as CD8+T cells and Thl cells and inhibit the occurrence and development of tumor by positively regulating cell adhesion and negative regulation of cell proliferation,and negatively regulating cell cycle and mitosis.In vitro experiments showed that overexpression of MS4A15 gene could inhibit the proliferation of LUAD,while had no significant effect on the migration of LUAD.ConclusionThis study found that MS4A15 plays a bi-directional regulatory role in the occurrence and development of many kinds of malignant tumors.In tumors with higher expression than normal tissues,MS4A15 may promote tumor development by regulating lipid metabolism and inhibiting immune infiltration,while in tumors with lower expression than normal tissues,MS4A15 may inhibit tumorigenesis by negatively regulating cell cycle and promoting immune infiltration,but its specific mechanism needs to be further studied.It is suggested that MS4A15 may be a potential prognostic marker for some tumors(including LUAD).