Conclusion
IgM AAbs are associated with early-stage colorectal cancer. Combining IgG, IgM and IgA AAbs is a novel strategy to improve early diagnosis of cancers.
Methods
We developed a novel protein array comprising 492 antigens seropositive in CRC. The array was used to profile IgG, IgM and IgA antibody signatures in 99 CRC patients and 99 sex- and age-matched non-cancer controls. A receiver operating curve (ROC), Kaplan-Meier survival analysis and univariate and multivariate Cox regression analyses were conducted.
Results
We identified a panel of 16 multi-isotype AAbs with a cumulative sensitivity of 91% and specificity of 74% (AUC 0.90, 95% CI: 0.850-0.940) across all CRC stages. IgM and IgG isotypes were conversely associated with disease stage with IgM contributing significantly to improved stage I and II sensitivity of 96% at 78% specificity (AUC 0.928, 95% CI: 0.884-0.973). A single identified IgA AAb reached an overall sensitivity of 5% at 99% specificity (AUC 0.520, 95% CI: 0.440-0.601) balanced across all CRC stages. Kaplan-Meier analysis revealed that se33-1 (ZNF638) IgG AAbs were associated with reduced 5-year overall survival (log-rank test, P = 0.012), whereas cumulative IgM isotype signatures were associated with improved 5-year overall survival (log-rank test, P = 0.024).