Abstract
COL12A1, a collagen type XII alpha 1 chain, has an instrumental role in the extracellular matrix (ECM), but its effect on gastric cancer (GC) and clinical significance remain unclear. In this study, co-expressed differentially expressed genes (co-DEGs) were identified using Venn diagrams based on datasets from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) for gastric cancer RNA sequencing. Intersections between co-DEGs and TCGA prognosis-related genes were used to pinpoint genes that were differentially associated with prognosis. COL12A1 emerged as a key candidate gene. We analyzed COL12A1 expression in human GC tissues and explored its association with various clinicopathological parameters. Survival analysis, including overall survival (OS) and disease-free survival (DFS), was conducted using TCGA data, and a prognostic nomogram was constructed. The relative protein-encoding gene expression was assessed via immunohistochemistry (IHC) analysis of four downloaded datasets, along with PCR experiments. COL12A1-related DEGs were further identified using the LinkedOmics database, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Multiple databases were analysed for the relationship between COL12A1 and methylation. Immune cell infiltration was evaluated through CIBERSORT and TIMER databases, revealing a strong correlation between COL12A1 expression and immune cell presence in the tumor microenvironment. Single-cell expression analysis using TISCH provided further insights into the cellular context of COL12A1 expression. TISCH was used to analyse the single-cell expression of COL12A1. Finally, this work examined the correlation of COL12A1 with drug sensitivity via the RNAactDrug database. COL12A1 overexpression in gastric cancer was detected and foundto be closely related to clinicopathological features. GO/KEGG functional enrichment analysis revealed that COL12A1 was associated with pathways such as extracellular structure organization, extracellular matrix organization and the collagen-containing extracellular matrix. Analysis of several databases revealed that COL12A1 was associated with gene mutation and methylation. Additionally, as revealed by CIBERSORT profiling and TIMER database analysis, COL12A1 expression is related to immune cell infiltration. Correlation analysis via the RNAactDrug website revealed that COL12A1 is associated with drug sensitivity. In conclusion, COL12A1 is significantly overexpressed in gastric cancer and is associated with tumor progression, immune infiltration, and drug sensitivity. These findings suggest that COL12A1 may serve as a potential diagnostic and therapeutic biomarker for gastric cancer.