Abstract
Background: The prognosis of patients with advanced cervical cancer remains unsatisfactory. A study indicated that transmembrane protein 33 (TMEM33) was implicated in tumor recurrence, while its role in cervical cancer has not been elucidated. Methods: TMEM33 expression in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) was primarily screened in The Cancer Genome Atlas (TCGA), and further validated in Gene Expression Omnibus (GEO) database. The Kaplan-Meier plotter analysis and Cox regression were constructed to evaluate the prognostic value of TMEM33 in CESC. Functional enrichment analysis was performed with GO, KEGG and GSEA tools. CCK-8 assay and colony formation assay were performed to investigate the carcinogenesis role of TMEM33 in cervical cancer cell proliferation. Results: TMEM33 expression was significantly elevated in CESC compared with normal tissues. High expression of TMEM33 was associated with poor prognostic clinical characteristics in CESC patients. KM-plotter analysis revealed that patients with increased TMEM33 had shorter overall survival (OS), progress free interval (PFI), and disease specific survival (DSS). Moreover, Multivariate Cox analysis confirmed that high TMEM33 expression was an independent risk factor for OS in patients with CESC. TMEM33 was associated with immune infiltrates, and its expression was correlated with tumorigenesis-related genes RNF4, OCIAD1, TMED5, DHX15, MED28 and LETM1. More importantly, knockdown of TMEM33 in cervical cancer cells decreased the expression of those genes and inhibited cell proliferation. Conclusion: Increased TMEM33 in cervical cancer can serve as an independent prognostic marker and might play a role in tumorigenesis by promoting cell proliferation.