title: Biomarkers as prognostic factors for cN2 or 3 non-small cell lung cancer treated by induction chemoradiotherapy and surgery.
abstract: BACKGROUND
  We have reported promising results of surgery after induction chemoradiotherapy (carboplatin-taxane, 50 Gy radiation) for cN2,3 non-small cell lung cancer (NSCLC). In order to understand the underlying mechanism, expression of excision repair cross-complementing 1 (ERCC1), class III β-tubulin (tubulin), thymidylate synthase (TYMS), and ribonucleotide reductase M1 (RRM1) were investigated.
  
  
  METHODS
  Immunohistochemistry was performed in 45 patients with cN2,3 NSCLC, but only in twelve pathologically-complete response cases to evaluate intratumoral expression of these biomarkers.
  
  
  RESULTS
  High expression of ERCC1, tubulin, TYMS and RRM1 was observed in 25 (55.6%), 19 (42.2%), 20 (44.4%) and 25 (55.6%) patients, respectively. Low expressions of ERCC1, tubulin, TYMS and RRM1 were favorable prognostic factors (p=0.044, p=0.025, p=0.039 and p=0.037, respectively). The simultaneously low expression of ERCC1 and tubulin was observed to be the most significant prognostic factor, by Cox regression analysis (hazard ratio=2.381; p=0.0059).
  
  
  CONCLUSIONS
  Patients with simultaneous low expression of ERCC1 and tubulin are promising candidates for surgery after carboplatin-taxane chemoradiotherapy. For patients with high expression of ERCC1 and tubulin, uracil-tegafur, pemetrexed, and gemcitabine may be the alternative agents for personalized chemotherapy.
authors.affiliation: Department of General Thoracic Surgery, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. yokomise@kms.ac.jp
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Yokomise
authors.forename: Dage
authors.initials: D
authors.lastname: Liu
authors.forename: Sungsoo
authors.initials: S
authors.lastname: Chang
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Go
authors.forename: Sinya
authors.initials: S
authors.lastname: Ishikawa
authors.forename: Nariyuki
authors.initials: N
authors.lastname: Misaki
authors.forename: Nariyasu
authors.initials: N
authors.lastname: Nakashima
mesh_terms: D000368:Aged; D015415:Biomarkers; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000401:mortality / Q000628:therapy*; D059248:Chemoradiotherapy; D004268:DNA-Binding Proteins / Q000032:analysis; D004720:Endonucleases / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012262:Ribonucleoside Diphosphate Reductase; D013940:Thymidylate Synthase / Q000032:analysis; D014404:Tubulin / Q000032:analysis; D025521:Tumor Suppressor Proteins / Q000032:analysis
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins; D014404:Tubulin; D025521:Tumor Suppressor Proteins; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; D013940:Thymidylate Synthase; C071447:ERCC1 protein, human; D004720:Endonucleases