Potential prognostic and predictive biomarkers: METTL5, METTL7A, and METTL7B expression in gastrointestinal cancers

The methyltransferase gene family is known for its diverse biological functions and critical role in tumorigenesis. This study aimed to identify these family genes in common gastrointestinal (GI) cancers using comprehensive methodologies.

Gene identification involved analysis of scientific literature and insights from The Cancer Genome Atlas (TCGA) database. RNA sequencing (RNA-seq) data for colon, gastric, pancreatic, esophageal, and liver cancers were collected, processed, and normalized. Differential expression analysis was conducted using R software with the Limma package. Additionally, real-time PCR analysis was performed on 30 tumor and 30 normal tissue samples from patients with colon and gastric cancer. Pathway analysis was conducted via the EnrichR web tool, while survival analysis used Cox regression methods, and biomarker potential was assessed with the pROC package. Prognostic significance was evaluated by examining associations between gene expression, patient survival, and recurrence rates. The study also investigated diagnostic potential through receiver operating characteristic (ROC) analysis, and assessed how small molecules affect gene expression, with implications for drug resistance and sensitivity, analyzed via CCLE and GDSC datasets.

Findings revealed METTL5 overexpression in colon, liver, esophagus, and pancreas cancers, while METTL7A was underexpressed in gastric, esophagus, liver, and colon cancers. METTL7B expression varied, being higher in gastric and esophagus cancers but lower in liver and colon cancers. Enrichment analysis identified pathways related to these genes, and survival analysis associated altered METTL7A and METTL5 expressions with poor prognosis and higher recurrence rates.

These findings suggest that METTL genes could serve as predictive biomarkers in GI cancers, offering potential implications for patient prognosis and treatment response.