Prognostic Impact of DNA Repair Protein Expression in Non-Small Cell Lung Cancers Treated with Platinum-Based Chemotherapy and Subsequent Curative Lung Resection

Oncology. 2018;95(1):20-30. doi: 10.1159/000488201. Epub 2018 Apr 25.

Abstract

Objective: Multimodal treatments that include preoperative platinum-based chemotherapy are fundamental to the treatment of advanced non-small cell lung cancer (NSCLC). This study aimed to investigate the predictive value of DNA repair protein expression in surgically resected NSCLCs in terms of prognosis and responses to platinum-containing chemotherapy.

Methods: This retrospective study included 136 patients with NSCLC who were treated with preoperative platinum-based chemotherapy, followed by curative lung resection. ATM, RAD51, LKB1, H2AX, and SIRT1 expression levels were analyzed in resected tumor specimens via immunostaining and were used to classify patients and compare survival and responses to chemotherapy.

Results: SIRT1 expression correlated significantly with improved responses to platinum-based chemotherapy (odds ratio, 2.28; p = 0.024), progression-free survival (hazard ratio [HR], 0.74; p = 0.036), overall survival (HR, 0.63; p = 0.006), and tumor-bearing survival (HR, 0.62; p = 0.014). After adjusting for clinical variables, the HR of SIRT1 expression remained significant for overall survival (HR, 0.59; p = 0.039) but not for progression-free survival (HR, 0.74; p = 0.183). No prognostic stratification was observed for the other 4 markers.

Conclusion: Patients with SIRT1-expressing NSCLC had superior responses to chemotherapy and longer survival durations than those with SIRT1-negative cancer.

Keywords: Biomarker; Non-small cell lung cancer; Platinum chemotherapy; Prognostic factor.

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Ataxia Telangiectasia Mutated Proteins / biosynthesis
  • Ataxia Telangiectasia Mutated Proteins / genetics
  • Biomarkers, Tumor / genetics*
  • Carboplatin / adverse effects
  • Carboplatin / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Cisplatin / adverse effects
  • Cisplatin / therapeutic use*
  • Combined Modality Therapy / methods
  • DNA Damage / drug effects
  • DNA Damage / genetics
  • DNA Repair / genetics
  • Disease-Free Survival
  • Female
  • Histones / biosynthesis
  • Histones / genetics
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Protein Serine-Threonine Kinases / biosynthesis
  • Protein Serine-Threonine Kinases / genetics
  • Rad51 Recombinase / biosynthesis
  • Rad51 Recombinase / genetics
  • Retrospective Studies
  • Sirtuin 1 / biosynthesis*
  • Sirtuin 1 / genetics*
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • H2AX protein, human
  • Histones
  • Carboplatin
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein Serine-Threonine Kinases
  • STK11 protein, human
  • AMP-Activated Protein Kinase Kinases
  • RAD51 protein, human
  • Rad51 Recombinase
  • SIRT1 protein, human
  • Sirtuin 1
  • Cisplatin