Pan-cancer analysis of TMEM45A and exploration of its prognostic value and mechanism in gastric cancer.

ABSTRACT

Cancer is a major category of diseases that need to be addressed urgently, bringing a huge burden to the world. Gastric cancer (GC) is a frequent malignant tumor of the digestive system with the highest incidence and mortality rate among all tumors. The purpose of this study was to explore the mechanism of action of TMEM45A in pan-cancer and gastric cancer. First, GEO and TCGA database were employed to analyze the expression of TMEM45A in GC patients. Then, we determined the association between TMEM45A expression and survival of GC patients using the Kaplan-Meier Plotter database and TCGA database and verified the accuracy of TMEM45A in predicting prognosis. Next, we analyzed the effect of CTHRC expression on TIICs in GC tissues. A prognostic model was constructed using immunomodulatory genes associated with TMEM45A. The specificity and accuracy of the model were verified. TMEM45A expression was markedly higher in GC tissue than in normal tissue. GC patients with TMEM45A overexpression had a poor prognosis. The AUC value of 5-year survival on the ROC curve was 0.705, indicating that TMEM45A is a reliable prognostic factor and can be used as a clinicopathological indicator alone to predict patient prognosis. Three high-risk immunomodulatory genes (CXCR4 and TGFB1) and one low-risk immunomodulatory gene (PDCD1) were obtained using both univariate and multivariate COX methods. These three immunomodulatory molecules were used to construct prognostic models. GC patients with TMEM45A overexpression have a poor prognosis and are associated with immune cell infiltration. Hence, TMEM45A is a fairly reliable independent prognostic marker.