Abstract
Background: Forkhead box P3 (FOXP3) has been found to be overexpressed by a range of cancer cells and correlated with prognosis of tumors. This finding raises the possibility that the development of anti-FOXP3 antibody test may be useful for clinical application. Objective: The present work was designed to test whether circulating autoantibody to FOXP3 was altered in lung cancer. Methods: 271 patients with non-small cell lung cancer (NSCLC) and 227 in control subjects matched in age, gender and smoking history were recruited. Circulating anti-FOXP3 IgG antibody was tested using an in-house enzymelinked immunosorbent assay. Results: Student’s t-test showed that the levels of IgG autoantibody to FOXP3 were significantly higher in patients with NSCLC than control subjects (t = 7.67, P 0.65 - 0.75, SE ± 0.024), in which patients at stage 2 had the highest AUC of 0.75 (95%CI 0.67 - 0.81, SE ± 0.037), with a sensitivity of 31.4% against a specificity of 90.3%. Analysis of quality control samples gave an inter-assay deviation of 13.3% among 45 plates tested. Conclusions: Circulating IgG autoantibody to FOXP3 may be a potential biomarker for lung cancer.
Highlights
A number of recent studies suggest that circulating autoantibodies to a particular tumor-associated antigen (TAA) are positive in some patients with malignant tumors [1-3] the TAAs involved in the specific immune response vary among tumor types and among individuals with a tumor
We developed an enzyme-linked immunosorbent assay (ELISA) inhouse using the human leukocyte antigen class II (HLA-II) restricted epitopes derived from Forkhead box P3 (FOXP3) to detect circulating anti-FOXP3 autoantibody
The levels of IgG autoantibody to FOXP3 were significantly higher in patients with lung cancer than control subjects (t = 4.99, P < 0.0001 for squamous cancer and t = 7.31, P < 0.0001 for adenocarcinoma); both male and female patients contributed to the increased levels of IgG autoantibody to FOXP3 circulating levels of anti-FOXP3 IgG was not significantly higher in female patients with squamous lung cancer (Table 1)
Summary
A number of recent studies suggest that circulating autoantibodies to a particular tumor-associated antigen (TAA) are positive in some patients with malignant tumors [1-3] the TAAs involved in the specific immune response vary among tumor types and among individuals with a tumor. CDTLung was the first autoantibody-based diagnostic tool in lung cancer [9] It was made with a panel of 7 TAAs and the panel antibody positivity has achieved up 50% in patients with lung cancer [9]. While the detection of circulating autoantibodies is a promising way for early diagnosis and prognosis of cancer, the improvement of sensitivity and specificity remains needed. To achieve this goal, it is important to identify new TAAs additive to the current panel. Forkhead box P3 (FOXP3) has been found to be overexpressed by a range of cancer cells and correlated with prognosis of tumors This finding raises the possibility that the development of anti-FOXP3 antibody test may be useful for clinical application. Conclusions: Circulating IgG autoantibody to FOXP3 may be a potential biomarker for lung cancer
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