Identifcation and Validation of EMT-immune-related Prognostic Biomarkers CMTM3 and LTBP2 in Gastric Cancer

Abstract Background. Gastric carcinoma (GC) is a common gastrointestinal tumor with high morbidity and mortality. The interaction between epithelial-mesenchymal transition (EMT) and immune microenvironment has important clinical significance. We aim to identify EMT-immune-related biomarkers in GC. Methods. We used GEO2R to calculate the differential expression genes (DEGs) between GC and normal mucosa. Immport, InnateDB and EMTome databases were used to define EMT-immune-related DEGs. We conducted batch prognostic analysis by GEPIA 2.0 and Kaplan-Meier plotter databases. The expression patterns were verified by multiple datasets and lab experiments. TCGA data, GEPIA, TIMER 2.0 and Tumor-immune system interaction database (TISIDB) databases were utilized to analyze the correlation of the hub genes with EMT markers and immune infiltration. Cancer Cell Line Encyclopedia(CCLE) database was used for co-expression and GO, KEGG, GSEA were used for enrichment analysis. Finally, the therapeutic sensitivity was analyzed. CMTM3, LTBP2 were up-regulated in GC and correlated with poor survival in different databases. Results. CMTM3 and LTBP2 were positively correlated with immune cell infiltration and immune checkpoints by the TIMER algorithm. By using the CIBERSORT algorithm, CMTM3 was positively correlated with the infiltration of macrophages (M2) and negatively correlated with dendritic cells activated, plasma cells. LTBP2 was negatively correlated with macrophages (M1), T cells CD4 + memory activated. Moreover, CMTM3 and LTBP2 were correlated with the EMT process. CMTM3 and LTBP2 could participate in the PI3K − Akt signaling pathway, TGF-β pathway and so forth. The expression of CMTM3 and LTBP2 may be judgments of the therapeutic sensitivity. Conclusion. Our work suggested the roles of CMTM3 and LTBP2 on prognosis, drug resistance, immune microenvironment and EMT process. They may be promising prognostic biomarkers and potential therapeutic targets in gastric carcinoma which deserves further study.