Objective: Both activin A, a member of transforming growth factor superfamily, and its inhibitor follistatin have been shown to be overexpressed in various cancers. We examined the expression of activin A and follistatin in tissue and blood samples from patients with oral squamous cell carcinoma.

Methods: The study population comprises 92 patients with oral squamous cell carcinoma. activin A and follistatin levels in tissues and sera were examined by qRT-PCR, immunohistochemistry and ELISA, respectively. Effects of activin A on oral cancer cells were investigated by trans-well migration/invasion assays and RNA interference.

Results: Overexpression of immunohistochemically detected activin A was correlated with positive N stage, poor histological differentiation, and perineural invasion (P = 0.029, 0.002, and 0.014, respectively). Statistical significant correlations between activin A and FST were observed in both mRNA and immunohistochemical expression (Pearson's correlation r = 0.507, P = 0.008 and r = 0.354 and P = 0.0005, respectively). In survival analyses, patients with oral squamous cell carcinoma whose tumors overexpressed activin A had a worse prognosis for overall survival and disease-free survival (P = 0.009 and 0.007). However, expression of follistatin in tumor was not correlated with overall survival or disease-free survival. Serum activin A and follistatin levels in 111 untreated patients were neither significantly different from those of 91 control samples nor associated with any clinicopathological manifestations. In vitro suppression of activin A expression in OC3 cells using specific interfering RNA attenuated cell proliferation, migration, and invasiveness.

Conclusion: These findings suggest that activin A overexpression in oral squamous cell carcinomas is associated with patients survival and may contribute to tumor progression and metastasis.

Citation Information: Clin Cancer Res 2010;16(7 Suppl):A16