title: Predictive value of APE1, BRCA1, ERCC1 and TUBB3 expression in patients with advanced non-small cell lung cancer (NSCLC) receiving first-line platinum-paclitaxel chemotherapy.
abstract: OBJECTIVE
  Drug resistance is not only one of the major obstacles to treatment but also a poor prognosis in advanced non-small cell lung cancer (NSCLC) patients. The aim of this study was to evaluate the predictive value of APE1, BRCA1, ERCC1 and TUBB3 in advanced NSCLC patients who received platinum-paclitaxel treatment.
  
  
  METHODS
  One hundred and thirty-six advanced NSCLC patients, who were treated with first-line platinum-paclitaxel chemotherapy, were enrolled in this study. The protein expression levels of APE1, BRCA1, ERCC1 and TUBB3 were assessed by immunohistochemistry and analyzed for the association with response to chemotherapy and progression-free survival (PFS) and overall survival (OS).
  
  
  RESULTS
  Patients with negative expression of APE1, ERCC1 or TUBB3 benefited from platinum plus paclitaxel regimen chemotherapy. ERCC1-negative patients had better PFS (P = 0.016) and OS (P = 0.030) compared with positive patients. Similarly, the APE1-negative patients showed better PFS (P = 0.004) and longer OS though statistically insignificant. Multivariate analysis showed that APE1 and ERCC1 were independent predictor for PFS (HR 2.07; P = 0.004 and HR 1.66; P = 0.016) and OS (HR 1.99; P = 0.008 and HR 1.64; P = 0.040). Moreover, patients with both APE1- and ERCC1-negative or both APE1- and TUBB3-negative tumors had significantly higher response rate, longer median PFS and OS following treatment with platinum and paclitaxel (P < 0.05).
  
  
  CONCLUSIONS
  The data indicate that APE1, ERCC1 and TUBB3 could be a useful biomarker to predict clinical outcome in patients with advanced NSCLC receiving first-line platinum-paclitaxel chemotherapy.
authors.affiliation: Cancer Center, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, No. 10 Changjiang Zhi Rd., Yuzhong District, Chongqing, 400042, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Qing
authors.forename: Wei
authors.initials: W
authors.lastname: Guan
authors.forename: Mengxia
authors.initials: M
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Peng
authors.forename: Shiheng
authors.initials: S
authors.lastname: Zhang
authors.forename: Yanli
authors.initials: Y
authors.lastname: Xiong
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols; D019313:BRCA1 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004260:DNA Repair / Q000187:drug effects; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011237:Predictive Value of Tests; D011379:Prognosis; D016896:Treatment Outcome; D014404:Tubulin / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D019313:BRCA1 Protein; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C498585:TUBB3 protein, human; D014404:Tubulin; C071447:ERCC1 protein, human; D004720:Endonucleases; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D017239:Paclitaxel; D002945:Cisplatin