title: Thiol/disulfide homeostasis: A prognostic biomarker for patients with advanced non-small cell lung cancer?
abstract: BACKGROUND
  The aim of this study was to investigate oxidative stress and thiol/disulfide status with a novel automated homeostasis assay in advanced non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Thirty-five patients with advanced NSCLC, who had been newly diagnosed and previously untreated, and 35 healthy subjects were chosen for the study. We measured plasma total thiol (-SH+-S-S-), native thiol (thiol) (-SH), and disulfide (-S-S-) levels in the patients with NSCLC and the healthy subjects. The thiol/disulfide (-SH/-S-S-) ratio was also calculated.
  
  
  RESULTS
  Statistically significant differences between the patient group and the control group were detected for the thiol/disulfide parameters. The mean native thiol, total thiol, and disulfide levels were significantly lower in the group with advanced stage NSCLC. The cut-off value was 313 and 13.8 for native thiol and disulfide, respectively. Median overall survival (OS) was significantly shorter in patients with low native thiol and disulfide levels according to the cut-off value (respectively, P = 0.001; P = 0.006). Native thiol, total thiol, and disulfide levels were correlated with Karnofsky performance status (KPS), OS, and age. Additionally, hierarchical regression analyses showed gender, KPS, lung metastases, and plasma native thiol levels were the determinants of OS in the final model.
  
  
  CONCLUSIONS
  These results suggest that in advanced stage NSCLC, the native thiol, total thiol, and disulfide levels decrease, while the native thiol/disulfide ratio does not change. Low levels of thiol/disulfide parameters are related to tumor aggressiveness and may predict a poor outcome for patients with NSCLC.
authors.affiliation: a Department of Chest Diseases, Medical Faculty , Suleyman Demirel University , Isparta , Turkey.
authors.forename: Nigar
authors.initials: N
authors.lastname: Dirican
authors.affiliation: b Department of Medical Oncology , State Hospital , Isparta , Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Dirican
authors.affiliation: c Department of Biochemistry , Ankara Ataturk Training and Research Hospital , Turkey.
authors.forename: Orhan
authors.initials: O
authors.lastname: Sen
authors.affiliation: d Department of Clinical Microbiology , Suleyman Demirel University , Isparta , Turkey.
authors.forename: Ayse
authors.initials: A
authors.lastname: Aynali
authors.affiliation: a Department of Chest Diseases, Medical Faculty , Suleyman Demirel University , Isparta , Turkey.
authors.forename: Sule
authors.initials: S
authors.lastname: Atalay
authors.affiliation: a Department of Chest Diseases, Medical Faculty , Suleyman Demirel University , Isparta , Turkey.
authors.forename: Haci Ahmet
authors.initials: HA
authors.lastname: Bircan
authors.affiliation: a Department of Chest Diseases, Medical Faculty , Suleyman Demirel University , Isparta , Turkey.
authors.forename: Onder
authors.initials: O
authors.lastname: Oztürk
authors.affiliation: e Department of Biochemistry , Ankara Numune Training and Research Hospital , Turkey.
authors.forename: Serpil
authors.initials: S
authors.lastname: Erdogan
authors.affiliation: a Department of Chest Diseases, Medical Faculty , Suleyman Demirel University , Isparta , Turkey.
authors.forename: Munire
authors.initials: M
authors.lastname: Cakir
authors.affiliation: a Department of Chest Diseases, Medical Faculty , Suleyman Demirel University , Isparta , Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Akkaya
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000378:metabolism* / Q000473:pathology*; D004220:Disulfides / Q000097:blood / Q000378:metabolism*; D005260:Female; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology; D011379:Prognosis; D017382:Reactive Oxygen Species / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000097:blood / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D004220:Disulfides; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds
keywords: Disulfide; Lung cancer; Oxidative stress; Prognosis; Thiol