p16 and p53 can Serve as Prognostic Markers for Head and Neck Squamous Cell Carcinoma.

OBJECTIVE: The present study aimed to explore the expression and clinical significance of human papilloma virus-related pathogenic factors (p16, cyclin D1, p53) in patients with head and neck squamous cell carcinoma (HNSCC) and construct a predictive model. METHODS: The Cancer Genome Atlas was used to obtain clinical data for 112 patients with HNSCC. Expression of p16, p53, and cyclin D1 was quantified. We used the survival package of the R program to set the cut-off value. Values above the cut-off were considered positive, while values below the cut-off were negative. Kaplan-Meier analysis and univariate and multivariate Cox regression analyses were performed to investigate prognostic clinicopathological indicators and the expression of p16, p53, and cyclin D1. A predictive model was constructed based on the results of multifactor Cox regression analysis, and the accuracy of the predictive model was verified through final calibration analysis. Follow-up of patients with HNSCC at the Affiliated Hospital of Binzhou Medical University was conducted from 2015 to 2017, and reliability of the predictive model was validated based on follow-up data and molecular expression levels. RESULTS: According to the results, expression of p16 and p53 was significantly associated with prognosis (P < .05). The predictive model constructed based on the expression levels of p16 and p53 was useful for evaluating the prognosis of patients with HNSCC. The predictive model was validated using follow-up data obtained from the hospital, and the trend of the follow-up results was consistent with the predictive model. CONCLUSION: p16 and p53 can be used as key indicators to predict the prognosis of HNSCC patients and as critical immunohistochemical indicators in clinical practice. The survival model constructed based on p16 and p53 expression levels reliably predicts patient prognosis.

Proliferation-associated 2G4 P48 is stabilized by malignant T-cell amplified sequence 1 and promotes the proliferation of head and neck squamous cell carcinoma.

Background/purpose: Proliferation-associated protein 2G4 (PA2G4) has alternative transcriptional and translational initiation. One dominant transcript ENST00000303305 could be translated into two protein isoforms (PA2G4-P42 and PA2G4-P48). In this study, we aimed to explore the effects of PA2G4-P42 and PA2G4-P48 on the proliferation of head and neck squamous cell carcinoma (HNSCC) and the mechanisms regulating PA2G4-P48 stability. Materials and methods: HNSCC cell lines HSC2 and SCC25 with relatively low PA2G4 expression were used for in-vitro cell studies. PA2G4-P42 and PA2G4-P48 overexpression lentiviruses were generated. In vitro cell proliferation was assessed by CCK-8 and colony formation. In vivo tumor cell proliferation was assessed by HSC2 cell-derived xenograft tumors. Liquid chromatography-mass spectrometry (LC-MS)/MS and co-immunoprecipitation (co-IP) assays were applied to check PA2G4-P48 interacting partners. Cycloheximide (CHX) chase and ubiquitin-based co-IP assays were also performed. Results: PA2G4-P48 was the dominant isoform, with substantially higher expression than PA2G4-P42 in HNSCC. PA2G4-P48 overexpression enhanced HNSCC cell proliferation, but PA2G4-P42 overexpression slowed the proliferation. MCTS1 interacted with PA2G4-P48, but not PA2G4-P42. PA2G4 protein but not its mRNA expression was decreased in cells with MCTS1 knockdown. MG132 treatment abrogated this alteration. MCTS1 overexpression significantly elevated the half-life of PA2G4-P48, while its knockdown drastically reduced the half-life compared with the control cells. In addition, MCTS1 overexpression significantly decreased the polyubiquitination of exogenous flag-tagged PA2G4-P48. MCTS1 overexpression-induced cell proliferation was hampered by knocking down of PA2G4-P48. Conclusion: PA2G4-P42 and PA2G4-P48 exert growth-suppressive and growth-promoting effects in HNSCC, respectively. MCTS1 can interact with PA2G4-P48 and prolong its half-life by reducing its poly-ubiquitination.