Identification and Validation of a Hypoxia-Immune-Based Prognostic mRNA Signature for Oral Squamous Cell Carcinoma

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a commonly encountered head and neck malignancy. Increasing evidence shows that there are abnormal immune response and chronic cell hypoxia in the development of OSCC. However, there is a lack of a reliable hypoxia-immune-based gene signature that may serve to accurately prognosticate OSCC. METHODS: The mRNA expression data of OSCC patients were extracted from the TCGA and GEO databases. Hypoxia status was identified using the t-distributed Stochastic Neighbor Embedding (t-SNE) algorithm. Both ESTIMATE and single-sample gene-set enrichment analysis (ssGSEA) were used for further evaluation of immune status. The DEGs in different hypoxia and immune status were determined, and univariate Cox regression was used to identify significantly prognostic genes. A machine learning method, least absolute shrinkage and selection operator (LASSO) Cox regression analysis, allowed us to construct prognostic gene signature to predict the overall survival (OS) of OSCC patients. RESULTS: A total of 773 DEGs were identified between hypoxia high and low groups. According to immune cell infiltration, patients were divided into immune high, medium, and low groups and immune-associated DEGs were identified. A total of 193 overlapped DEGs in both immune and hypoxia status were identified. With the univariate and LASSO Cox regression model, eight signature mRNAs (FAM122C, RNF157, RANBP17, SOWAHA, KIAA1211, RIPPLY2, INSL3, and DNAH1) were selected for further calculation of their respective risk scores. The risk score showed a significant association with age and perineural and lymphovascular invasion. In the GEO validation cohort, a better OS was observed in patients from the low-risk group in comparison with those in the high-risk group. High-risk patients also demonstrated different immune infiltration characteristics from the low-risk group and the low-risk group showed potentially better immunotherapy efficacy in contrast to high-risk ones. CONCLUSION: The hypoxia-immune-based gene signature has prognostic potential in OSCC.