Multi-omic profiling identifies KRT1 as a predictor of immune infiltration and prognosis in gastroesophageal junction cancer

Gastroesophageal junction cancer (GEJ) is typically investigated alongside gastric or esophageal cancers. However, separate molecular profiles and immune cell infiltration of GEJ remain largely unknown. This study screened for hub genes in GEJ, studied their function and regulation in biological processes, and investigated their relationship with the infiltration of immune cells into tumors. Datasets were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus public databases. Molecular profiling revealed significant down-regulated expression of key genes in GEJ and enrichment in pathways related to epithelial cell differentiation and development, and structural constituents of skin epidermis. Prognostic analysis showed that patients with low KRT1, Desmocollin 2, and Envoplakin expression had a worse prognosis. There was a strong correlation between the levels of KRT1 and both the tumor mutational burden and immune cell infiltration. Single gene pathway enrichment analysis and in vitro experiments confirmed that cancer cell proliferation, migration, and invasion were suppressed by KRT1 via the AKT/mTOR pathway. In conclusion, this multi-dimensional study analyzed the molecular alterations and oncological mechanisms underlying the progression of GEJ. KRT1 is a promising candidate biomarker for the molecular and immunological characterization of GEJ and for prognosis prediction.