Overexpression of CDK7 is associated with unfavourable prognosis in oral squamous cell carcinoma.

Increased expression of cyclin-dependent kinase 7 (CDK7), an ubiquitous kinase associated with cell cycle and transcription, contributes to human tumourigenesis and associates with patients' prognosis. In the present study, we sought to investigate the expression pattern of CDK7 and its clinicopathological significance in primary oral squamous cell carcinoma (OSCC). The expression of CDK7 mRNA in OSCC was determined by data mining and interrogation using the Oncomine database. Its protein expression was measured by immunohistochemistry in clinical samples from a retrospective cohort of 113 patients with primary OSCC which were treated at our institution from January 2006 to December 2016. The potential associations between CDK7 abundance and multiple clinicopathological parameters as well as patients' survival were assessed. The 4-nitroquinoline 1-oxide (4NQO)-induced OSCC mouse model was developed to monitor CDK7 expression during cancer initiation and progression. The bioinformatics analyses revealed higher CDK7 mRNA in OSCC samples compared to normal counterparts. Our immunohistochemical staining data revealed significant aberrant overexpression of CDK7 in a large subset of OSCC. Elevated CDK7 expression was found to be significantly associated with higher T-stage (p = 0.009) and reduced overall and disease-free survival (Log-rank test, p = 0.022, 0.010, respectively). Both univariate and multivariate Cox regression analysis identified the expression status of CDK7 as an important independent prognostic factor for patients' survival. Increased CDK7 expression was parallel with OSCC development in the 4NQO-induced animal model. Our findings indicate that aberrant CDK7 overexpression associates with T-stage and reduced survival in OSCC, thus suggesting that it might play critical roles underlying oral tumourigenesis and also serve as a novel biomarker with diagnostic and prognostic significance.

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