METTL7A as a New Candidate Biomarker in Gastric Cancer by Genomics and Data-Independent Acquisition Proteomic Analysis.

Background: Early diagnosis and intervention are essential for improving the prognosis and survival of gastric cancer (GC) patients. However, specific biomarkers for early GC diagnosis are still unavailable.

Methods: Data-independent acquisition (DIA) proteomics was employed to identify differentially expressed proteins (DEPs) between GC and adjacent non-tumor tissues. Functional and pathway enrichment analyses were conducted, with subsequent genomic-level validation. Methyltransferase-like 7A (METTL7A) expression in GC versus adjacent tissues was confirmed via tissue microarray analysis. Correlations between METTL7A expression, clinical characteristics, and immune infiltration were also explored. Additionally, co-expressed genes related to METTL7A were analyzed, and gene set variation analysis (GSVA) was performed.

Results: DIA proteomics identified 84 DEPs, mainly involved in protein binding and enriched in complement and coagulation pathways. Eight DEPs overlapped with results from the gene expression omnibus (GEO) dataset. METTL7A expression was significantly lower in GC tissues compared to adjacent tissues, confirmed at the genomic level. The cancer genome atlas (TCGA) analysis revealed an area under the receiver operating characteristic (ROC) curve (AUC) of 0.81, with METTL7A expression inversely correlated with age (p = 7.307e-05). Tissue microarray analysis further confirmed reduced METTL7A expression in GC tissues (p = 0.000). METTL7A expression was positively correlated with activated B cells and negatively correlated with activated CD4 T cells.

Conclusions: METTL7A is a promising biomarker for early GC diagnosis.