Concomitant overexpression of Activin A and p63 is associated with poor outcome in oral cancer patients

Background The present study aims to comprehensively analyze expression of Activin signaling components in oral cancer and to determine the predominant Activin expressed and its influence on prognosis. As our preliminary studies indicated regulation of Activin gene by p63, we also propose to assess its correlation with p63/p53 in oral tumors and its impact on outcome. Methods Expression of Activin subunits, receptors, and regulators was assessed by qRT-PCR and Western blotting. Correlation between Activin A and p63/p53 expression was evaluated in oral tumors by immunohistochemistry and their association with clinical outcome was determined by Kaplan-Meier curves and Cox regression. Results Activin beta A transcripts were upregulated (P = .013) in oral dysplastic and cancer cells compared with normal oral mucosa. Expression of Activin receptors and regulators was also altered. Activin beta A protein was significantly upregulated in oral tumors and adjacent normal tissues compared with normal oral mucosa (P < .0001). Expression of Activin beta A and p63 significantly correlated in oral tumors, correlation being stronger in tumors with high p53 (r = -.394,P = .005). Activin beta A overexpression was associated with advanced tumor stage (P = .021), positive nodes (P = .045), poor recurrence-free survival (P = .013), and overall survival (P = .024), while its concomitant overexpression with p63 was a better predictor of recurrence-free survival (HR = 10.66, CI: 1.41-80.19). Conclusions Activin A overexpression is an early event in oral cancer pathogenesis and can independently predict survival. Moreover, in combination with p63 overexpression, it served as a better marker for poor prognosis. Activin A could thus be a promising target for improved outcome in oral cancer patients.