A protein fragment derived from DNA-topoisomerase I as a novel tumour-associated antigen for the detection of early stage carcinoma

Br J Cancer. 2016 Dec 6;115(12):1555-1564. doi: 10.1038/bjc.2016.369. Epub 2016 Nov 22.

Abstract

Background: The production of autoantibodies against tumour-associated antigens (TAAs) is believed to reflect greater immunologic reactivity in cancer patients and enhanced immune surveillance for cancer cells. Over the past few decades, a number of different TAAs and their corresponding autoantibodies have been investigated. However, positive frequency of autoantibody detection in cancer patients has been relatively low. Here we describe a novel TAA that was a fragment derived from human DNA-topoiomerase I and an autoantibody against the novel TAA with relatively high positive frequency in the sera of early-stage non-small-cell lung cancer (NSCLC), gastric cancer (GC), colorectal cancer (CRC) and oesophageal squamous cell carcinoma (ESCC).

Methods: Serologic enzyme-linked immunosorbent assay (ELISA) and western blot were used to discover a novel TAA with a molecular weight of 48 kDa separated by ion exchange chromatography. Autoantibody ELISA, immnohistochemistry and immunofluorescent staining, recombinant protein cloning/expression and western blot were used to identify the novel TAA. The association of the autoantibody against the novel TAA with early-stage carcinoma was explored by screening 203 stage I/II patients and 170 stage III/IV patients with NSCLC, GC, CRC or ESCC.

Results: We identified the novel TAA as a fragment derived from human DNA-topoiomerase I (TOP1). We found that the novel TAA induced specific autoantibodies with a high prevalence that ranged from 58 to 72% in some of the most common types of cancer. We observed that the immune response against the novel TAA was associated with early stage ESCC, GC, CRC and NSCLC.

Conclusions: The findings in this study suggest that the autoantibody against the novel TAA may be a potential biomarker for use in the early detection and diagnosis of cancer.

MeSH terms

  • Antigens, Neoplasm / immunology*
  • DNA Topoisomerases, Type I / metabolism*
  • Early Diagnosis
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Neoplasms / diagnosis*
  • Neoplasms / immunology

Substances

  • Antigens, Neoplasm
  • DNA Topoisomerases, Type I