Abstract B224: HPV-stratified analysis of prognostic role of miR-21 in oropharyngeal squamous cell carcinoma.

Background: Both smoking and human papillomavirus (HPV) infection play an significant role in the development and progression of oropharyngeal squamous cell carcinoma (OSCC). MicroRNAs are short noncoding RNAs that regulate multiple mRNAs and are frequently dysregulated in cancer. The miR-21 microRNA is overexpressed in a wide variety of cancers and has been causally related to cellular proliferation and apoptosis. In this study, we investigated the association between the expression of miR-21 and the clinicopathologic features by stratified analysis based on HPV infection status. Patients and Methods: The expression of miR-21 in the OSCC tissues of 137 patients was evaluated by in situ hybridization method. In addition, PDCD4 and PTEN were also examined by immunohistochemistry using tissue microarray. The clinicopathological implications of these molecules were analyzed statistically. Results: The up-regulation of miR-21 expression was 22.7% for HPV negative group and 42.1% for HPV positive group (P = 0.081), and significantly correlated with advanced lymph node metastasis and extracapsular extension (P = 0.005 and P = 0.014, respectively). There was a significant association between miR-21 and cytoplasmic PDCD4 overexpression (P = 0.027). Kaplan-Meier analysis showed that up-regulation of miR-21 was significantly related with shorter overall survival (OS; 77.0 v 193.0 months; P =0.05) in HPV-negative OSCC, but not in HPV-positive OSCC (P =0.95). At HPV-stratified multivariate analysis, up-regulation of miR-21 was independent prognostic factor for both relapse-free survival (RFS; HR, 2.681; 95% CI, 1.090 to 6.591; P = 0.032) and OS (HR, 6.286; 95% CI, 2.047 to 19.302; P = 0.001). Conclusion: Up-regulation of miR-21 expression is closely associated with poor prognosis in HPV-negative OSCC, but not in HPV-positive OSCC, suggesting that miR-21 may have a different role according to the HPV infection status. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B224. Citation Format: Yoon Ho Ko, Ho Jung An, Der Sheng Sun, Hye Sung Won, Jin Hyoung Kang, Chan-Kwon Jung. HPV-stratified analysis of prognostic role of miR-21 in oropharyngeal squamous cell carcinoma. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B224.