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 if 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.
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