Comprehensive analysis of COMMD10 as a novel prognostic biomarker for gastric cancer.

BACKGROUND

COMMD10 has an important role in the development of certain tumors, but its relevance to gastric cancer (GC) is unclear. The purpose of this study is to investigate the difference of COMMD10 expression in gastric adenocarcinoma (STAD) and analyze the correlation between COMMD10 expression and prognosis of STAD patients.

METHODS

The expression levels of COMMD10 between STAD and normal tissues were explored using the The Cancer Genome Atlas (TCGA) database. In addition, the expression of COMMD10 in GC was further validated by immunohistochemistry (IHC) staining, qRT-PCR and Western blot. Dot blot experiments were used for exploring m6A expression levels in tissues with high and low COMMD10 expression. Kaplan-Meier analysis and COX regression analysis were used to explore the relationship between COMMD10 and STAD prognosis. A nomogram was constructed to predict the survival probability of STAD patients. GO and KEGG functional enrichment of COMMD10-related genes were performed. The Corrlot software package was used to analyze the correlation between COMMD10 expression levels and m6A modifications in STAD. An analysis of immune infiltration based on the CIBERSOFT and the single-sample GSEA (ssGSEA) method was performed.

RESULTS

COMMD10 expression was significantly associated with multiple cancers, including STAD in TCGA. COMMD10 expression was elevated in STAD cancer tissues compared to paracancerous tissues. COMMD10 upregulation was associated with poorer overall survival (OS), clinical stage, N stage, and primary treatment outcome in STAD. Functional enrichment of COMMD10-related genes was mainly involved in biological processes such as RNA localization, RNA splicing, RNA transport, mRNA surveillance pathways, and spliceosomes. The dot blot experiment showed that m6A levels were higher in cancer tissues with high COMMD10 expression compared with paracancerous tissues. COMMD10 was significantly correlated with most m6A-related genes. COMMD10 was involved in STAD immune cells infiltration, correlated with macrophage cells expression.

CONCLUSION

High COMMD10 expression was significantly associated with poor prognosis in STAD patients, and its functional realization was related to m6A modification. COMMD10 involved in STAD immune infiltration.