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

Autor: Zhen-bo Hu, Jie Zeng, Shang-mian Yie, Cheng-lu Yang, Mei Cao, Ke Xie, Shang-rong Ye, Jia Zhang, Jian-bo Zhang, Xiao-li Ma, Xu He
Rok vydání: 2016
Předmět:
Zdroj: British Journal of Cancer
ISSN: 1532-1827
0007-0920
DOI: 10.1038/bjc.2016.369
Popis: 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.
Databáze: OpenAIRE
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