Multiomics Analysis of COL12A1 as a Promising Prognostic Biomarker for Immune-Related Treatment of Gastric Cancer

Abstract

Abstract COL12A1 has an instrumental role in the extracellular matrix (ECM), but its effect on gastric cancer (GC) as well as the clinical significance remains unclear. The co-expression differential genes (co-DEGs) were acquired from Venn diagrams via The Cancer Genome Atlas (TCGA) as well as Gene Expression Omnibus (GEO) stomach RNAseq dataset. Intersection between co-DEGs and TCGA prognosis-related genes was used to to pinpoint genes differentially associated with prognosis. The COL12A1 gene was selected as the key factor for the present work. COL12A1 level within human GC was analyzed in relation to its clinicopathological characteristics, and the TCGA database was adopted for plotting overall survival (OS) together with disease-free survival (DFS) curves, and the prognostic column. The relative protein gene expression was assessed by Human Protein Atlas (HPA) database, four downloaded datasets, along with PCR experiments. Differentially expressed genes (DEGs related to COL12A1 were detected via LinkedOmics, and subject to GO as well as KEGG analysis based on related genes. The cBioPortal and Catalogue of Somatic Mutations in Cancer databases were first utilized for the expression and identification of COL12A1-correlated mutation analysis. Multiple databases were analyzed for the relationship between COL12A1 and methylation. COL12A1 was examined using the Tumor Immune Estimation Resource (TIMER) database for identifying association of COL12A1 gene level with stomach adenocarcinoma-infiltrating immune cells. Finally, this work examined correlation of COL12A1 with drug sensitivity with RNAactDrug database. COL12A1 over-expression within gastric cancer was detected, which was closely related to clinicopathological features. GO/KEGG functional enrichment analysis revealed that COL12A1 was associated with pathways like extracellular structure organization, extracellular matrix organization and collagen-containing extracellular matrix. The analysis of several databases revealed that COL12A1 was associated with gene mutation and methylation. Additionally, as revealed by CIBERSORT profiling and TIMER database, COL12A1 expression related to immune cell infiltration. Correlation analysis through the RNAactDrug website revealed that COL12A1 is associated with drug sensitivity. COL12A1 can be a diagnostic and therapeutic biomarker for GC, which may be associated with tumor immune infiltration and drug sensitivity.