title: Poor response to platinum-based chemotherapy is associated with KRAS mutation and concomitant low expression of BRAC1 and TYMS in NSCLC.
abstract: OBJECTIVE
  To evaluate treatment response, survival, and the associations between KRAS mutation status and tumour expression levels of BRCA1, TYMS and SRC retrospectively in a cohort of patients with non-small cell lung cancer (NSCLC), treated exclusively with conjunctive platinum-based doublet chemotherapy.
  
  
  METHODS
  KRAS mutation status was determined via amplification refractory mutation and multiple quantitative polymerase chain reaction (PCR) analysis. Tumour expression levels of BRCA1, TYMS and SRC were determined via real time quantitative PCR.
  
  
  RESULTS
  Patients with KRAS mutations (n = 3) had significantly shorter survival duration than patients with wild type KRAS (n = 42). Tumour expression levels of BRCA1 and TYMS, but not SRC, were significantly lower in patients with, than in those without, KRAS mutations. Tumour expression level of BRCA1 was positively correlated with survival duration.
  
  
  CONCLUSIONS
  KRAS mutation status and BRCA1 tumour expression are potential biomarkers for tailoring chemotherapy and predicting clinical outcome.
authors.affiliation: Department of Oncology, Liyang People's Hospital, Liyang, Jiangsu, China.
authors.forename: Hongxuan
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Liyang People's Hospital, Liyang, Jiangsu, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Department of Surgery, Liyang People's Hospital, Liyang, Jiangsu, China.
authors.forename: Liqun
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Oncology, Liyang People's Hospital, Liyang, Jiangsu, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Oncology, Liyang People's Hospital, Liyang, Jiangsu, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Fei
authors.affiliation: Department of Oncology, Liyang People's Hospital, Liyang, Jiangsu, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Pan
authors.affiliation: Department of Oncology, Liyang People's Hospital, Liyang, Jiangsu, China.
authors.forename: Juxiang
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Oncology, Liyang People's Hospital, Liyang, Jiangsu, China.
authors.forename: Xianqing
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Oncology, Liyang People's Hospital, Liyang, Jiangsu, China.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Oncology, Liyang People's Hospital, Liyang, Jiangsu, China.
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Tao
authors.affiliation: Department of Surgery, Liyang People's Hospital, Liyang, Jiangsu, China sph@sina.com.
authors.forename: Pinghuai
authors.initials: P
authors.lastname: Shi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics* / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics*; D003710:Demography; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010984:Platinum / Q000494:pharmacology / Q000627:therapeutic use*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013940:Thymidylate Synthase / Q000235:genetics* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; C117307:KRAS protein, human; D012333:RNA, Messenger; D010984:Platinum; C000600377:TYMS protein, human; D013940:Thymidylate Synthase; D016283:Proto-Oncogene Proteins p21(ras)
keywords: BCA1; KRAS; Nonsmall cell lung cancer (NSCLC); TYMS; drug response; overall survival; platinum doublets