Detection of circulating natural antibodies against CD25, MUC1, and VEGFR1 for early diagnosis of non-small cell lung cancer

Abstract

We previously demonstrated that a deficiency of natural antibodies against CD25, Mucin 1 (MUC1), and vascular endothelial growth factor receptor 1 (VEGFR1) could contribute to high risk of non-small cell lung cancer (NSCLC). This study was designed to investigate whether natural IgG antibodies against POU domain class 5 transcription factor 1 (POU5F1), tumor necrosis factor-α (TNF-α), and the combination of CD25, VEGFR1, and MUC1 could play an anti-tumorigenic role against developing NSCLC. An ELISA was developed in-house to examine plasma IgG against peptide antigens derived from POU5F1, TNF-α, and a combination of peptide antigens derived from CD25, MUC1, and VEGFR1 in 211 patients with NSCLC and 200 healthy controls. Mann-Whitney U test demonstrated that plasma IgG levels for the combination of peptide antigens derived from CD25, MUC1, and VEGFR1 were significantly lower in NSCLC patients than control subjects (Z = -12.978, P < 0.001) although plasma levels of IgG antibodies for POU5F1 and TNFα were not significantly changed. The in-house ELISA made with the CD25-MUC1-VEGFR1 combination had a sensitivity of 49.6% against a specificity of 95% to detect early-stage NSCLC. In conclusion, natural antibodies against the combination of CD25, VEGFR1, and MUC1 may be an effective biomarker for early diagnosis of NSCLC.

Keywords: CD25; MUC1; VEGFR1; natural antibody; non-small cell lung cancer.

Fig. 1

Receiver operating characteristic curve analysis of circulating IgG levels in three subgroups of NSCLC. Group I for stages 1 and 2A, group II for stage 2B, and group III for stages 3 and 4. (A) The CD25‐MUC1‐VEGFR1 IgG assay with a specificity of 95% showed an AUC of 0.883 (95% CI 0.844–0.923) with a sensitivity of 49.6% in group I, an AUC of 0.861 (95% CI 0.804–0.918) with a sensitivity of 39.0% in group II, and an AUC of 0.846 (95% CI 0.785–0.907) with a sensitivity of 26.5% in group III. (B) The POU5F1 IgG assay with a specificity of 95% showed an AUC of 0.582 (95% CI 0.516–0.648) with a sensitivity of 10.7% in group I, an AUC of 0.566 (95% CI 0.470–0.663) with a sensitivity of 7.3% in group II, and an AUC of 0.518 (95% CI 0.429–0.607) with a sensitivity of 2.0% in group III.