title: 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.
  
  
  CONCLUSIONS
  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.affiliation: Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Azuma
authors.affiliation: Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan.|Department of Pharmacology and Oncology, Graduate School of Medicine, Gunma University, Maebashi, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Yokobori
authors.affiliation: Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Mogi
authors.affiliation: Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan.
authors.forename: Bolag
authors.initials: B
authors.lastname: Altan
authors.affiliation: Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Yajima
authors.affiliation: Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kosaka
authors.affiliation: Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Onozato
authors.affiliation: Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan.
authors.forename: Ei
authors.initials: E
authors.lastname: Yamaki
authors.affiliation: Department of Oncology Clinical Development, Gunma University, Maebashi, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Asao
authors.affiliation: Department of Pharmacology and Oncology, Graduate School of Medicine, Gunma University, Maebashi, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Nishiyama
authors.affiliation: Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kuwano
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000188:drug therapy; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry* / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D017024:Chemotherapy, Adjuvant; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D037761:Sirtuins / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; C516592:SIRT6 protein, human; D037761:Sirtuins
keywords: autophagy; chemoresistance; sirtuin; sirtuin 6