An Autoantibody Against Human DNA-Topoisomerase I Is a Novel Biomarker for Non-Small Cell Lung Cancer

Ann Thorac Surg. 2018 Jun;105(6):1664-1670. doi: 10.1016/j.athoracsur.2018.01.036. Epub 2018 Feb 14.

Abstract

Background: We previously reported a novel tumor-associated antigen with a molecular weight of approximately 48 kDa that was a fragment derived from human DNA-topoisomerase I. The aim of this study is to further investigate the clinical significance of the autoantibody in patients with non-small cell lung cancer (NSCLC).

Methods: We determined serum levels of the autoantibody in 127 NSCLC patients, 127 age-, sex-, and smoking history-matched healthy control subjects, and 38 patients with pulmonary benign tumors by using a specific enzyme linked immunosorbent assay for the autoantibody. We then statistically evaluated its clinical application value.

Results: Serum levels of the autoantibody in NSCLC patients were significantly higher than in healthy control subjects and patients with benign tumors (p = 0.001). The percentage of sera with a positive level of the autoantibody was 71.8%, 65.6%, 41.9%, and 48.0% in stages I, II, III, and IV of the cancer, respectively (p = 0.049). The area under the receiver-operating characteristics curve was 0.971 (95% confidence interval: 0.953 to 0988) for healthy controls and patients with benign tumors versus early stage NSCLC patients. Moreover, the overall survival rate of the patients in stages I, II, and IV with negative levels of the autoantibody was significantly lower than that of patients with positive levels of the autoantibody (p = 0.013, 0.023, and 0.047 for stages I, II, and IV, respectively).

Conclusions: Our results indicate that the autoantibody can be used as a novel biomarker for the early diagnosis and prognosis of NSCLC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Autoantibodies / blood*
  • Autoantibodies / immunology
  • Biomarkers, Tumor / blood*
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / immunology*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Case-Control Studies
  • DNA Topoisomerases, Type I / blood*
  • DNA Topoisomerases, Type I / immunology
  • Disease-Free Survival
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / blood
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Prognosis
  • ROC Curve
  • Reference Values
  • Risk Assessment
  • Statistics, Nonparametric
  • Survival Analysis

Substances

  • Autoantibodies
  • Biomarkers, Tumor
  • DNA Topoisomerases, Type I