Circulating anti-p16a IgG autoantibodies as a potential prognostic biomarker for non-small cell lung cancer

It has been reported that p16 protein is overexpressed in many types of solid cancer and its aberrant expression may trigger the immune response, leading to the secretion of anti-p16 antibodies. Here, we developed an in-house ELISA with three p16-derived linear peptide antigens to examine plasma anti-p16 antibody levels in patients with non-small cell lung cancer (NSCLC). Blood samples were taken from 200 control subjects and 211 patients with NSCLC prior to anticancer therapy. A Mann-Whitney U test demonstrated that plasma anti-p16a IgG levels were significantly higher in NSCLC patients than in control subjects (Z = -11.14, P < 0.001). However, neither plasma anti-p16b nor plasma anti-p16c IgG levels showed significant differences in patients with NSCLC as compared to control subjects. Moreover, further analysis indicated that anti-p16a IgG levels increased with tumor stages, and patients with late stage NSCLC, namely group IV, had the highest IgG levels among four subgroups. Receiver operating characteristic analysis revealed that the anti-p16a IgG assay had a sensitivity of 32.7% against a specificity of 95.0% in group IV, while Kaplan-Meier survival analysis revealed no significant difference in overall survival between patients with high anti-p16a IgG levels and those with low anti-p16a IgG levels (χ²  = 0.24, P = 0.63). In conclusion, anti-p16a IgG may be suitable for use as a prognostic biomarker for NSCLC.