Loss of the clock gene PER2 is associated with cancer development and altered expression of important tumor-related genes in oral cancer

Abstract

Recent studies have demonstrated that abnormal expression of the clock gene PER2 is closely associated with the development of a variety of cancer types. However, the expression of PER2 in oral squamous cell carcinoma (OSCC), a common malignant tumor in humans, and its correlations with the clinicopathological parameters and survival time of OSCC patients and the altered expression of important tumor-related genes remain unclear. In the present study, we detected the mRNA and protein expression levels of PER2, PIK3CA, PTEN, P53, P14ARF and caspase‑8 in OSCC tissues and cancer-adjacent oral mucosa by reverse transcription-quantitative PCR (RT-qPCR), western blotting and immunohistochemistry. The results showed that the PER2, PTEN, P53, P14ARF and caspase‑8 mRNA and protein expression levels in OSCC were significantly reduced compared with those in cancer-adjacent tissues. Additionally, the PIK3CA protein expression level was significantly increased in OSCC tissues, whereas the mRNA level was not. Decreased expression of PER2 was significantly associated with advanced clinical stage and the presence of lymphatic metastasis in OSCC patients. Patients with PER2‑negative expression had a significantly shorter survival time than those with PER2‑positive expression. PER2 expression was negatively correlated with PIK3CA and P53 levels, and positively correlated with PTEN, P14ARF and caspase‑8 levels. In summary, the results of this study suggest that loss of PER2 expression is closely associated with the genesis and development of OSCC and that PER2 may be an important prognostic biomarker in OSCC. PER2 may serve an antitumor role via the P53/P14ARF, PIK3CA/AKT and caspase‑8 pathways.