Exploration of mRNA-modifying METTL3 oncogene as momentous prognostic biomarker responsible for colorectal cancer development.

Abstract

Background: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, emphasizing the need for improved prognostic biomarkers. Recent studies have identified the mRNA-modifying METTL3 oncogene as a potential biomarker in CRC progression.

Objective: This study aimed to investigate the expression patterns of METTL3 in CRC, assess its association with clinical outcomes, identify interacting proteins and biological pathways, and explore its correlation with immune cell infiltration.

Methods: Comprehensive analyses were conducted using public datasets, including transcriptome profiles from The Cancer Genome Atlas and the GSE103512 dataset. Protein-protein interaction (PPI) networks, pathway enrichment, and immune infiltration analyses were performed to elucidate METTL3's role in CRC progression.

Results: METTL3 expression was significantly higher in CRC tissues compared to normal tissues (p < 0.001). Mutations in METTL3 were detected in approximately 6% of CRC cases, with fusion events involving the SRPK2 gene. PPI analysis identified ten interacting proteins, including METTL4, EIF3H, RBM15B1, CBLL1, WTAP, NCBP1, RBM15, ZC3H13, METTL14, and KIAA1429. METTL3 expression showed a positive correlation with METTL4, METTL14, NCBP1, and WTAP expression (R > 0.5, p < 0.001). Higher METTL3 expression was associated with immunosuppressive phenotypes, such as increased infiltration of tumor-associated macrophages, regulatory T cells, and cancer-associated fibroblasts (p < 0.001). Pathway enrichment analysis revealed METTL3's involvement in crucial pathways, including the cell cycle and renal cell carcinoma (p < 0.01). Gene ontology analysis highlighted its role in mRNA and RNA-related processes.

Conclusion: The study supports the potential of METTL3 as a prognostic biomarker in CRC and highlights its involvement in immune modulation and cancer progression. These findings lay the groundwork for future studies aimed at developing targeted therapies and improving patient outcomes.