A transmembrane protein family gene signature for overall survival prediction in osteosarcoma

Abstract

The transmembrane (TMEM) protein family is constituted by a large number of proteins that span the lipid bilayer. Dysregulation of TMEM protein genes widely occurs and is associated with clinical outcomes of patients with multiple tumors. Nonetheless, the significance of TMEM genes in the prognosis prediction of patients with osteosarcoma remains largely unclear. Here, we comprehensively analyzed TMEM protein family genes in osteosarcoma using public resources and bioinformatics methods. Prognosis-related TMEM protein family genes were identified by the univariate Cox regression analysis and were utilized to construct a signature based on six TMEM protein family genes (TMEM120B, TMEM147, TMEM9B, TMEM8A, TMEM59, and TMEM39B) in osteosarcoma. The prognostic signature stratified patients into high- and low-risk groups, and validation in the internal and external cohorts confirmed the risk stratification ability of the signature. Functional enrichment analyses of differentially expressed genes between high- and low-risk groups connected immunity with the prognostic signature. Moreover, we found that M2 and M0 macrophages were the most abundant infiltrated immune cell types in the immune microenvironment, and samples of the high-risk group showed a decreased proportion of M2 macrophages. Single-sample gene set enrichment analysis revealed that the scores of neutrophils and Treg were markedly lower in the high-risk group than these in the low-risk group in The Cancer Genome Atlas and GSE16091 cohorts. As for the related immune functions, APC co-inhibition and cytolytic activity exhibited fewer active levels in the high-risk group than that in the low-risk group in both cohorts. Of the six TMEM genes, the expression of TMEM9B was lower in the high-risk group than in the low-risk group and was positively associated with the overall survival of osteosarcoma patients. In conclusion, our TMEM protein family gene-based signature is a novel and clinically useful prognostic biomarker for osteosarcoma patients, and TMEM9B might be a potential therapeutic target in osteosarcoma.

Prognostic value of TMEM147 in hepatocellular carcinoma correlates with immune infiltration of hepatocellular carcinoma

“…Based on the current study showing a signi cant increase in TMEM147 expression in colon cancer, it may be substantially involved in the pathogenesis of colon cancer [19]. In osteosarcoma, TMEM147 expression was negatively correlated with patient prognosis [20]. Several studies have shown that the function of the endoplasmic reticulum is closely related to hepatocellular carcinoma, but TMEM147 has not been reported in hepatocellular carcinoma.…”

“…It has been shown experimentally that TMEM147 has a broader effect on transmembrane proteins in the endoplasmic reticulum and nuclear envelope, and turns TMEM147 into many additional putative regulator processes and a potential therapeutic target for a range of diseases [34]. Although not all the functions of TMEM147 are understood, in the current literature it has been shown that TMEM147 plays an important role in colon cancer pathogenesis [19] and osteosarcoma prognosis [20].…”

Transmembrane protein 147, as a potential Sorafenib target, could expedite cell cycle process and confer adverse prognosis in hepatocellular carcinoma

“…Increased TMEM147 expression was reported in colon cancer and osteosarcoma as a potential prognostic factor 20,30 . Xiang Rui Li et al found TMEM147 was expressed in goat PBMC and could mediate cell proliferation, apoptosis, and secretion of cytokines 31 .…”

“…However, its cancer‐involving roles have not received sufficient attention. Wei Xie et al constructed a prognostic model composed of six TMEM protein family genes for osteosarcoma patients, but TMEM147 as the least important variable in the LASSO equation presented no significant difference between the tumor and normal groups 30 . Zhi Chen et al confirmed the prognostic implication and altered expression of TMEM147 in colon cancer, but the interpretation of functional enrichment analyses remained speculative 20 .…”

“…Increased TMEM147 expression was reported in colon cancer and osteosarcoma as a potential prognostic factor. 20,30 Xiang Rui Li et al…”