TMEM40 serves as a potential prognostic biomarker and therapeutic target in colorectal cancer

Transmembrane protein 40 (TMEM40) is a transmembrane protein implicated in several tumor types, yet its role in colorectal cancer (CRC) remains unclear. Transcriptomic and clinical data of CRC were obtained from the TCGA cohort and GEO datasets (GSE23878, GSE39582, GSE110225, GSE38832 and GSE37892) to analyze the expression pattern of TMEM40 in CRC. Survival analysis and nomogram modeling were performed to evaluate its prognostic relevance. Subsequently, functional enrichment analysis was conducted to identify key signaling pathways, and immune infiltration analysis was carried out to explore the relationship between TMEM40 and the tumor immune microenvironment. Finally, CCK-8, transwell, and western blot assays were used to validate the biological function and potential molecular mechanisms of TMEM40 in CRC cells. Across all CRC cohorts, TMEM40 expression was markedly elevated and its high expression strongly associated with poorer overall survival, serving as an independent prognostic factor for CRC. Functional analyses indicated that TMEM40 is involved in regulating the Wnt signaling pathway and protein export pathway. Immune profiling revealed that high TMEM40 expression correlates with increased monocyte infiltration and upregulation of immune checkpoint molecules, including CD274, CTLA-4, and CD86. Functional assays further demonstrated that TMEM40 knockdown significantly suppressed CRC cell viability, proliferation, and migration. Mechanistically, TMEM40 may promote CRC progression by activating the Wnt signaling pathway and enhancing exosome-mediated HSPA5 secretion. TMEM40 plays a critical role in the development and progression of CRC and holds promise as a potential diagnostic and prognostic biomarker.