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

Abstract

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.

• Authors: Yoko Azuma, Takehiko Yokobori, Akira Mogi, Bolag Altan, Toshiki Yajima, Takayuki Kosaka, Ryoichi Onozato, Ei Yamaki, Takayuki Asao, Masahiko Nishiyama, Hiroyuki Kuwano
• Journal: Journal of surgical oncology (J Surg Oncol) Vol. 112 Issue 2 Pg. 231-7 (Aug 2015) ISSN: 1096-9098 [Electronic] United States
• PMID: 26180037 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 Wiley Periodicals, Inc.

Chemical References

• Biomarkers, Tumor
• SIRT6 protein, human
• Sirtuins

Topics

• Adenocarcinoma (chemistry, drug therapy)
• Adenocarcinoma of Lung
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers, Tumor (analysis)
• Blotting, Western
• Carcinoma, Non-Small-Cell Lung (chemistry, drug therapy, pathology)
• Cell Line, Tumor
• Chemotherapy, Adjuvant
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Lung Neoplasms (chemistry, drug therapy, pathology)
• Male
• Middle Aged
• Neoplasm Staging
• Predictive Value of Tests
• Prognosis
• Radiotherapy, Adjuvant
• Sirtuins (analysis)