Over-expression of Transmembrane Protein 158 Predicts Aggressive Tumor Behavior and Poor Prognosis in Lung Cancer

Background/Aim: Transmembrane protein 158 (TMEM158) has emerged as a potential contributor to cancer progression. While TMEM158 has been studied in various cancer types, its role in lung cancer remains unclear. Materials and Methods: Kaplan–Meier curves were used to evaluate the association between TMEM158 expression and overall survival rates. Gene set enrichment analysis (GSEA) was performed to explore pathways related to TMEM158, and sequence analysis was conducted to identify putative hypoxia-responsive element (HRE) sites in the TMEM158 promoter region. Hypoxic conditions were induced, and TMEM158 expression levels were measured by qPCR. The effect of hypoxia-inducible factor-1α (HIF-1α) depletion on TMEM158 expression was also examined. Additionally, lung cancer cells with either over-expressed or reduced TMEM158 levels were analyzed for epithelial-mesenchymal transition (EMT) and cell migration. Results: Analysis of clinical datasets revealed elevated TMEM158 expression in tumors, particularly in patients with advanced stages. High TMEM158 expression was correlated with lower overall survival. TMEM158 was associated with EMT, hypoxia, and other tumor-promoting pathways. Under hypoxic conditions, TMEM158 expression was at least partially induced in a HIF-1α-dependent manner. Functional studies showed that over-expression of TMEM158 promoted EMT and increased lung cancer cell migration, while depletion of TMEM158 reduced these effects, indicating its role in aggressive tumor behavior. Conclusion: TMEM158 is highly expressed in lung cancer, is associated with hypoxia, and promotes EMT and cell migration. These findings suggest TMEM158 as a potential target for lung cancer therapies.