Hepatitis B X-interacting protein, involved in increasing proliferation and cell migration, is a prognostic marker in head and neck squamous cell carcinoma

Introduction: Factors associated with prognosis and molecular mechanisms leading to a malignant phenotype in head and neck squamous cell carcinoma (HNSCC) need to be identified. The focus was on the biological function and clinical impact of hepatitis B X-interacting protein (HBXIP) in HNSCC. Methods: mRNA expression profiles of HBXIP were compared between tumor and normal tissues in head and neck cancer cases from an online database. The protein expressions of candidate genes were verified by immunohistochemistry (IHC) with tissue microarray blocks designed with 221 cases. Prognostic significance was analyzed using the Kaplan-Meier method and Cox regression analysis. The molecular function of malignant phenotypes was investigated by generating knockdown cell lines of HNSCC with RNA interference. Results: Analysis of the online database showed that the mRNA of HBXIP was significantly higher in the HNSCC group than in normal specimens. IHC analysis showed significant differences in the protein expression of HBXIP by clinical stage, T status, and recurrence. Multivariate analysis showed that, in HBXIP IHC-positive patients, N status, T status, and neural invasion were significantly associated with overall survival. In addition, downregulation of the HBXIP gene in SAS, a tongue squamous cancer cell line, inhibited proliferation and the invasion phenotype. Conclusions: By increasing the malignant phenotypes of cell proliferation and invasion, upregulation of HBXIP was a prognostic factor in HNSCC.