Abstract
Background: The oncological role of TMC5 in human cancers has only been revealed partially. We performed integrated bioinformatics analysis to provide a thorough and detailed insight of associations between TMC5 and tumorigenesis, cancer progression, and prognosis. Methods: With reference to the accessible online databases, the TMC5 expressions in tumor tissues and corresponding normal tissues, different pathological stages, and various cancer cells were analyzed, while the protein levels of TMC5 in different cancers were also inspected. Meanwhile, the prognostic value of TMC5 expression in multiple cancers as well as in advanced-stage patients was investigated. Furthermore, the mutational data of TMC5 and its correlation with cancer prognosis were assessed. Moreover, the association between the TMC5 level and immune cell infiltration was evaluated. Next, TMC5-related pathway alterations and drug responses were summarized. Finally, the TMC5 based protein network was generated, and relevant enrichment was performed. Results: In our study, the expression level of TMC5 was significantly higher in the tumor tissue than that of the normal tissues in most cancer types. Fluctuations of TMC5 levels were also observed among different pathological stages. In the meantime, the protein level elevated in the tumor tissue in the cancers enrolled. Moreover, the expression of TMC5 was not only prognostic for overall survival (OS) or recurrence free survival (RFS) in various types of cancers but also correlated to OS in patients with more advanced cancers. Additionally, the mutational status of TMC5 is also associated with prognosis in cancer patients. It is worth noting that the TMC5 level was closely related to immune cell infiltrations, especially in ESCA, TGCT, and USC. The TMC5 expression was also identified as an activator for pathways including PI3K/AKT, RAS/MAPK, and TSC/mTOR, proved to be associated with multiple drug responses and assessed to be interactive with the TMEM family. Conclusion: TMC5 might function as a potential marker for cancer survival and immune responses.
Highlights
The transmembrane channel (TMC)–like family includes 8 members (TMC1 to TMC8)
The mutational status of TMC5 is associated with prognosis in cancer patients
TMC7 was identified as a potential prognostic biomarker for pancreatic cancer (Cheng et al, 2019); the same association was discovered between TMC8 and hepatocellular carcinoma (HCC) (Lu et al, 2017), TMC4, and breast cancer (Aushev et al, 2019), TMC3 and colorectal cancer (CRC) (Zhou et al, 2020), TMC8 and head and neck squamous cancer (Lin et al, 2021)
Summary
Various studies demonstrated a close relation between the TMC family and human cancers. As a member of the TMC family, TMC5 was detected to be related to human cancers. TMC5 is correlated with tumor microenvironments in HCC and associated with prognosis in HCC and lung adenocarcinoma (LUAD) (Arroyo et al, 2020; Pan et al, 2020). Whether the oncologic role of TMC5 was limited to certain cancers or broadly applicable is still not clear; we carried out a bioinformatics analysis to offer a comprehensive view. The oncological role of TMC5 in human cancers has only been revealed partially. We performed integrated bioinformatics analysis to provide a thorough and detailed insight of associations between TMC5 and tumorigenesis, cancer progression, and prognosis
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