Downregulated Expression of RIPOR3 Correlated with Immune Infiltrates Predicts Poor Prognosis in Oral Tongue Cancer

Background: Tongue cancer is the most prevalent of head and neck squamous cell carcinomas, including base of tongue cancer (BOT) and oral squamous cell carcinoma of the mobile tongue (OTSCC). We aimed to investigate the role of RIPOR3 in tumorigenesis and its development as a potential prognostic biomarker for tongue cancer, especially OTSCC. Material/Methods: Associations of expression, clinical pathologic features, and overall survival were analyzed by logistic regression, multivariate Cox analysis, and Kaplan-Meier methods. Gene set enrichment analysis (GSEA) and the CIBERSORT algorithm were performed to determine the correlation between RIPOR3 and tumor immune infiltration. cBioPortal was used for methylation and copy number variation (CNV) analysis. The Human Protein Atlas (HPA) and GSE31056 dataset were used for further external validation. Results: RIPOR3 expression in OTSCC was significantly associated with various clinicopathological parameters. Kaplan Meier survival analysis showed that OTSCC with low RIPOR3 expression had a worse prognosis than that with high RIPOR3 expression. Multivariate analysis revealed that lower RIPOR3 expression was an independent prognostic factor for poor prognosis. GSEA and Neighbor Gene Network analysis showed RIPOR3 expression was related with the modulation and function of the immune-related pathway. Methylation level and CNV analysis showed that the downregulated expression of RIPOR3 was significantly related to hypermethylation but not to CNV. Finally, high RIPOR3 expression was validated at the protein level using the HPA database and GSE31056 dataset. Conclusions: These findings suggested that RIPOR3 might serve as a promising prognostic biomarker and is related to the immune cell infiltration of OTSCC.