Circulating autoantibody to FOXP3 may be a potential biomarker for esophageal squamous cell carcinoma
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RESEARCH ARTICLE
Circulating autoantibody to FOXP3 may be a potential biomarker for esophageal squamous cell carcinoma Leiguang Ye & Songlei Guan & Cong Zhang & Kuang-Hui Lee & Shilong Sun & Jun Wei & Baogang Liu
Received: 14 January 2013 / Accepted: 27 February 2013 / Published online: 13 March 2013 # International Society of Oncology and BioMarkers (ISOBM) 2013
Abstract The present study was undertaken to develop a relatively quantitative enzyme-linked immunosorbent assay (ELISA) in-house using human leukocyte antigen class IIrestricted epitopes in order to test circulating autoantibodies to human forkhead/winged helix transcription factor (FOXP3) as a biomarker for esophageal cancer. A total of 97 patients with esophageal squamous cell carcinoma (ESCC) and 227 healthy subjects were recruited for this study, and their plasma samples were collected for antibody analysis with the ELISA approach. Student’s t test showed that the anti-FOXP3 IgG antibody levels were significantly higher in the patient group than the control group (t=6.23, P95 % specificity was 22.7 % for the IgG assay with an inter-assay deviation of 13.35 %. This work suggests that circulating IgG autoantibody to FOXP3 may be a potential biomarker for early diagnosis of esophageal cancer. Keywords Autoantibodies . FOXP3 . Tumor immunity . Esophageal squamous cell carcinoma
Introduction Esophageal cancer is an aggressive and lethal malignancy of the esophagus. Its incidence rates vary between countries, with a cumulative risk of 0.8 % in more developed areas and 1.4 % in less developed areas [1]. It is the sixth most frequent cause of cancer death worldwide [2] and the fourth leading cause of cancer death in China [3]. There are two common subtypes of esophageal cancer, squamous cell carcinoma that accounts for approximately 90 % of all esophageal cancer and adenocarcinoma that accounts for less than 10 %. The prognosis of esophageal cancer is quite poor, and 5-year survival rates range between 15 and 34 % [4]. Accordingly, there is an urgent need for identification of biomarkers for early diagnosis of esophageal cancer and for development of effective therapy. Forkhead/winged helix transcription factor (FOXP3) is a member of the forkhead/winged helix family of transcriptional factors [5]. FOXP3 is involved in regulating the immunosuppressive function of regulatory T lymphocytes (Treg) in autoimmune response [6]. Treg cells largely express FOXP3 and the alpha chain of interleukin 2 receptor, also known as CD25. It has long been noted that Treg cells play an important role in tumor immunity, and their recruitment is
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involved in promoting cancer cells to escape from host protective immunity [7]. Increased CD4+CD25+ cell numbers and FOXP3 mRNA expression have been found in advanced esophageal cancer [8]. Interestingly, a number of recent studies have revealed that FOXP3 is expressed not only by Treg cells but also by a range of human cancer cells [9–14], suggesting that FOXP3 expressed in cancer cells may act as a tumor-associated antigen (TAA)
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