A Pan-cancer Analysis of the Role of the Transmembrane Protein 91(TMEM91) in Human Tumors

Abstract

Transmembrane protein 91(TMEM91) encodes a protein belonging to the transmembrane protein family which mediates many human physiological processes, such as the regulation of cell migration and invasion, and participates in the immune response. At present, research on the TMEM family members focuses mostly on the field of molecular mechanisms, and the role of TMEM91 in tumor cells is still unrecognized. Using data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, we can analysis the expression of TMEM91 in various tumors. The Kaplan-Meier method was used for the evaluation of the prognostic significance of TMEM91 in patients with pan-cancer. The dif-ferential expression of TMEM91 in diverse cancers with different clinical characteristics was analyzed with the UALCAN database. TIMER was used to explore how TMEM91 correlates with immune infiltration. The correlations between TMEM91 expression immune checkpoint (ICP), tumor mutational burden (TMB), and microsatellite instability (MSI) in human cancers were analyzed via the SangerBox database. Gene Set Cancer Analysis (GSCA) platform was used to investigate the correlation between TMEM91 expression with Copy number variations (CNV) and methylation. Protein-Protein Interaction analysis was performed in the GeneMANIA database. Gene Ontology and Kyoto Encyclopedia of Genes pathway en-richment analyses were further conducted for exploration of TMEM91 function. According to the finding of this study, downregulated TMEM91 expression was observed in numerous tumor tissues. The low TMEM91 expression group showed poor overall survival (OS) and disease-free survival (DFS). TMEM91 was positively correlated with can-cer-associated fibroblast (CAF), and nature killer T cell (NKT), and negatively correlated with CD4 + T cells, B cells and common lymphoid progenitor (CLP). Here, we show that there is a positive relationship between Contingent Negative Variation (CNV) and expression of TMEM91, whereas the correlation of TMEM91 expression with DNA methylation was nega-tive in all cases. Molecular biology experiments were performed to confirm the tumor pro-moting role of TMEM91 in glioma. Function analysis showed that TMEM91 expres-sion-related genes were mainly enriched in response to type I interferon /regulation of viral genome replication/negative regulation of viral process/movement in host environment. In addition, the association between the expression of TMEM91 and the use of the anticancer drug, sensitive anti-tumor drug based on CellMiner were predicted, such as the anticancer drug AS-703569, Hydroxyurea. Our pan-cancer analysis provides a deep understanding of the functions of TMEM91.TMEM91 may affect the oncogenesis and metastasis in different cancers via mediating the immune infiltrating cells and the degree of methylation. This study sheds new light on the mechanism of TMEM family in cancer.