SIRT6 expression is associated with poor prognosis and chemosensitivity in patients with non-small cell lung cancer

• Published in: Journal of surgical oncology Vol. 112; no. 2; pp. 231 - 237
• Main Authors: Azuma, Yoko, Yokobori, Takehiko, Mogi, Akira, Altan, Bolag, Yajima, Toshiki, Kosaka, Takayuki, Onozato, Ryoichi, Yamaki, Ei, Asao, Takayuki, Nishiyama, Masahiko, Kuwano, Hiroyuki
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.08.2015; Wiley Subscription Services, Inc
• Subjects: Adenocarcinoma - chemistry; Adenocarcinoma - drug therapy; Adenocarcinoma of Lung; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; autophagy; Biomarkers, Tumor - analysis; Blotting, Western; Carcinoma, Non-Small-Cell Lung - chemistry; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Cell Line, Tumor; chemoresistance; Chemotherapy, Adjuvant; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Lung cancer; Lung Neoplasms - chemistry; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Middle Aged; Neoplasm Staging; Predictive Value of Tests; Prognosis; Radiotherapy, Adjuvant; sirtuin; sirtuin 6; Sirtuins - analysis; chemoresistance; autophagy; sirtuin 6; sirtuin
• ISSN: 0022-4790; 1096-9098
• DOI: 10.1002/jso.23975

Background Despite advances in the development of various therapeutic agents, non‐small cell lung cancer (NSCLC) is associated with a poor prognosis. To improve the prognosis of patients with NSCLC, new therapeutic targets for overcoming drug resistance are required. The process of autophagy is required to support the tumorigenesis and drug resistance of cancer cells. We investigated the clinical significance of SIRT6, a member of the NAD+‐dependent deacetylase family, which regulates a variety of cancer‐related processes, including autophagy. Methods Immunohistochemistry analysis of SIRT6 expression and localization in 98 NSCLC clinical specimens and in vitro analysis using SIRT6‐knockout lung carcinoma cell lines were performed. Results Patients with high cytoplasmic expression and low nuclear expression of SIRT6 (n = 33) had more aggressive cancer, shorter overall survival, and shorter recurrence‐free survival than did patients with different SIRT6 expression profiles (P < 0.05). In vitro analysis revealed that SIRT6 knockdown lung adenocarcinoma cell line improved paclitaxel sensitivity (P < 0.05) and reduced the expression levels of both nuclear factor kappaB and autophagy marker Beclin1. Conclusion Our data demonstrated that SIRT6 expression in NSCLC could be a useful prognostic marker and that SIRT6 might represent a novel target gene for predicting sensitivity of chemotherapy in lung adenocarcinoma. J. Surg. Oncol. 2015 111:231–237. © 2015 Wiley Periodicals, Inc.