Abstract 732: Overexpression of the basic helix-loop-helix protein DEC1 induces cellular senescence and is related to better survival in esophageal squamous cell carcinoma

Abstract

Abstract Objective: Human differentiated embryo chondrocyte expressed gene 1 (Dec1), also known as Bhlhb2/Stra13/Sharp-2, is a basic helix-loop-helix transcription factor that involves in cell proliferation, differentiation, apoptosis, and cellular senescence. In this study, the expression, function, diagnosis and prognostic impact of DEC1 in normal esophageal epithelia, esophageal squamous cell carcinoma (ESCC) and its precursor lesions (intraepithelial neoplasia) were investigated. Methods: ESCC combined with adjacent precursor tissues from 241 patients were collected to construct tissue microarray (TMA) blocks. DEC1 expression among normal epithelia, introepithelial neoplasia and ESCC was analyzed by immunohistochemistry (IHC), and the correlations between Dec1 and clinicopathological parameters were also analyzed statistically. In vitro study, DEC1 was transient transfected into ESCC cell line EC9706, and then cellular senescence was analyzed by senescence associated β-galactosidase (SA-α-Gal) activity. Fresh esophagectomy tissues from ESCC patients were embedded and fixed, and tissue sections were detected by immunohistochemistry of DEC1 and SA-α-Gal activity. Results: Compared with normal epithelia, DEC1 expression was significantly increased in intraepithelial neoplasia and DEC1 expression was significantly decreased in ESCC in comparison with intraepithelial neoplasia. DEC1 overexpression both induced cellular senescence in EC9706 cell line and correlated to more senescent cells in fresh tissue sections. Kaplan - Meier method analysis revealed that DEC1 expression levels were significantly correlated with the survival of ESCC patients after surgery. The expression levels of DEC1 were also correlated with the tumor embolus, depth of invasion of ESCC, lymph metastasis status and pTNMs. Conclusions: These results suggest that DEC1 overexpression is a protective mechanism by inducing cellular senescence in ESCC progression, and DEC1 is a potential prognostic marker of ESCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 732. doi:1538-7445.AM2012-732