title: Mutations of EGFR or KRAS and expression of chemotherapy-related genes based on small biopsy samples in stage IIIB and IV inoperable non-small cell lung cancer.
abstract: OBJECTIVE
  Epidermal growth factor receptor (EGFR) and KRAS mutations may predict the outcome of targeted drug therapy and also may be associated with the efficacy of chemotherapy in patients with non-small cell lung cancer (NSCLC). This report investigated the relation of EGFR or KRAS mutation and expression of chemotherapy-related genes, including excision repair cross-complementing 1 (ERCC1), thymidylate synthetase (TYMS), ribonucleotide reductase subunit M1 (RRM1) and class III β-tubulin (TUBB3), as a potential explanation for these observations.
  
  
  METHODS
  A total of 143 patients with stage IIIB and IV NSCLC from bronchoscopy or percutaneous lung biopsy obtained tumor samples were analyzed concurrently for EGFR or KRAS mutations, and mRNA expression of ERCC1, TYMS, RRM1 and TUBB3. EGFR or KRAS mutations were detected with xTAG liquidchip technology (xTAG-LCT), and mRNA expression levels of four genes were detected by branched DNA-liquidchip technology (bDNA-LCT).
  
  
  RESULTS
  Of 143 patients, 63 tumors were positive for EGFR-activating mutations, and 16 tumors were positive for KRAS mutations. EGFR-activating mutations are more frequent in females, adenocarcinoma and non-smokers patients, and KRAS mutations are more frequent in smoking patients. ERCC1 mRNA levels were significantly associated with histological type and tumor differentiation, whereas TYMS levels were significantly associated with age. NSCLC specimens that harboring EGFR-activating mutations are more likely to express low ERCC1 and high TUBB3 mRNA levels, whereas tumors from patients with NSCLC harboring KRAS mutation are more likely to express high ERCC1 mRNA levels.
  
  
  CONCLUSIONS
  Mutations and expression of chemotherapy-related genes may provide a basis for the selection of suitable molecular markers for individual treatment in a population with stage IIIB and IV NSCLC.
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, Heilongjiang, People's Republic of China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Deng
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Deng
authors.forename: Chang-Lian
authors.initials: CL
authors.lastname: Lu
authors.forename: Yang
authors.initials: Y
authors.lastname: Guo
authors.forename: Di
authors.initials: D
authors.lastname: Wang
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Yan
authors.forename: Xing
authors.initials: X
authors.lastname: Lv
authors.forename: Yu-Xia
authors.initials: YX
authors.lastname: Shao
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics; D004720:Endonucleases / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012333:RNA, Messenger / Q000032:analysis; D012262:Ribonucleoside Diphosphate Reductase; D013940:Thymidylate Synthase / Q000235:genetics; D014404:Tubulin / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D018631:ras Proteins / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C498585:TUBB3 protein, human; D014404:Tubulin; D025521:Tumor Suppressor Proteins; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; D013940:Thymidylate Synthase; D066246:ErbB Receptors; C071447:ERCC1 protein, human; D004720:Endonucleases; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins