Bioinformatics Unveils Key Genes in the MAPK Pathway in Colorectal Cancer and Predicts Prognosis, Immune...

The Mitogen-Activated Protein Kinase (MAPK) signaling pathway is significant in clinical practice for its potential to impede tumor proliferation and migration and to enhance patient prognosis. Yet, the specific contributions of MAPK-related genes to the prognosis of colorectal cancer (CRC) are not clear.

CRC data was retrieved from TCGA and GEO databases, with the MAPK pathway genes being identified from Kyoto Encyclopedia of Genes and Genomes (KEGG). A risk signature model for CRC associated with the MAPK pathway was formulated using regression analysis. The tumor immune microenvironment of high- and low-risk groups was assessed using single sample gene set enrichment analysis (ssGSEA) and CIBERSORT algorithms. We also looked into the potential differential response to immunotherapy by comparing immune checkpoints, immunophenoscore (IPS) scores, and Tumor Immune Dysfunction and Exclusion (TIDE) scores between the two groups. Moreover, the sensitivity to CRC treatment drugs in high- and low-risk groups was probed by forecasting drug IC50 values with the pRRophetic R package.

A risk model was established using eight distinct genes (CDC42, CACNA1D, EREG, TRAF2, MAPKAPK3, DDIT3, NGF, TGFB2) identified from the differential expression of MAPK-related genes. The analysis highlighted that patients in the high-risk group had a higher degree of immune cell infiltration but were less sensitive to immunotherapy (indicated by higher TIDE and lower IPS scores). Drug sensitivity predictions suggested that the high-risk group, despite their poor immunotherapy response, had an increased sensitivity to drugs such as Pazopanib, WH-4-023, and WZ-1-84.

To encapsulate our findings, we have determined eight MAPK pathway-associated CRC prognostic biomarkers and developed a prognostic model accordingly. This model has proven effective in stratifying the risk levels among CRC patients.