title: Dual Specificity Phosphatase 6 (DUSP6) Polymorphism Predicts Prognosis of Inoperable Non-Small Cell Lung Cancer after Chemoradiotherapy.
abstract: BACKGROUND
  Dual-specificity phosphatase 6 (DUSP6) inactivates different target kinases to regulate cell proliferation and differentiation. Altered DUSP6 expressions or gene polymorphisms are associated with human cancer development including non-small cell lung cancer (NSCLC). DNA topoisomerase II alpha (TOP2A) regulates chromosome condensation and chromatid separation, and altered TOP2A expressions are associated with drug resistance development. This study assessed DUSP6 and TOP2A single nucleotide polymorphisms (SNPs) associated with NSCLC patient survival.
  
  
  METHODS
  This study included 152 surgically resected NSCLC patients and 277 chemoradiotherapy treated inoperable cases. DNA samples from each patient were genotyped for DUSP6 and TOP2A SNPs. Kaplan-Meier survival analysis, log-rank test, and Cox proportional hazard model were used to evaluate the association between these variants and NSCLC overall survival.
  
  
  RESULTS
  DUSP6 rs2279574 A/A genotype was associated with significantly poor inoperable NSCLC patient overall survival (A/A vs. C/C, adjusted HR = 1.549, 95% CI = 1.019-2.355). Stratification analysis against clinical stage, histology, weight loss, and ECOG performance status revealed that the DUSP6 rs2279574 A/A variant homozygous genotype is associated with a decrease in survival of stage IV NSCLC patients compared to those with the C/C genotype (log-rank, p = 0.003). No association was found among histology, weight loss, and ECOG performance status. Moreover, there was no association of TOP2A SNPs between clinicopathological and survival data.
  
  
  CONCLUSIONS
  Data obtained from the current study demonstrated that functional DUSP6 rs2279574 polymorphism was able to predict inoperable NSCLC patient survival after chemoradiotherapy.
authors.forename: Tian-Lu
authors.initials: TL
authors.lastname: Wang
authors.forename: Ying-Qiu
authors.initials: YQ
authors.lastname: Song
authors.forename: Yang-Wu
authors.initials: YW
authors.lastname: Ren
authors.forename: Bao-Sen
authors.initials: BS
authors.lastname: Zhou
authors.forename: He-Tong
authors.initials: HT
authors.lastname: Wang
authors.forename: Lu
authors.initials: L
authors.lastname: Bai
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.forename: Yu-Xia
authors.initials: YX
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D059248:Chemoradiotherapy; D054642:Dual Specificity Phosphatase 6 / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: C517035:DUSP6 protein, human; D054642:Dual Specificity Phosphatase 6