Abstract LB407: Enhancing sensitivity and specificity of the CA15-3 (MUC1) breast cancer assay by detection of N-glycolylneuraminic acid (Neu5Gc) using the lectin SubB2M

Abstract Introduction: The aim of this study was to test the hypothesis that the diagnostic performance (as defined by the classification accuracy, sensitivity and specificity) of CA15-3 to detect breast cancer is increased by detection of the cancer-associated Neu5Gc sialic acids on the mucin MUC1 using the novel lectin, SubB2M. Methods A genetically engineered lectin (SubB2M) that binds Neu5Gc was used as a detection reagent in a sandwich ELISA format CA15-3 assay. In a case : control cohort equivalence study the classification accuracy for the SubB2M-based CA15-3 assay (neuCA15-3) was determined and compared to an FDA-approved CA15-3 IVD test (Elecsys CA15-3 II, Roche Diagnostics). Results Classification accuracy and AUC for neuCA15-3 were 81% and 0.886 ± 0.015 (standard error, n=567) and for Elecsys Ca15-3 II, 55% and 0.642 ± 0.023 (n=558), respectively. At a threshold cut-off serum concentration of 23.6 Units/ml, overall breast cancer classification accuracy of the neuCA15-3 was 81% (compared to 55% for the comparator assay, p < 0.001). At 95% specificity, the sensitivity of the NeuCA15-3 assay was 69.5%, significantly greater than the competitor assay (11.9%, p<0.001). NeuCA15-3 concentrations did not vary significantly with breast cancer receptor subtype. Conclusions The diagnostic performance of the neuCA15-3 assay was substantially improved over the classical CA15-3 sandwich assay that detects all forms of MUC1. The reporter signal generated for the neuCA15-3 assay depends on capture of the MUC1 protein and the presence of the aberrant Neu5Gc sialic acid residues on the MUC1 protein, thus increasing the assay specificity. The presence of multiple Neu5Gc lectin binding sites per glycoprotein molecule increases signal generation and assay sensitivity. The inclusion of additional cancer biomarkers in a multivariate index assay format may further increase diagnostic performance for breast cancer. Citation Format: Sara Nikseresht, Ramin Khanabdali, Lucy Shewell, Christopher Day, Amy McCart Reed, Michael Jennings, Haarika Haarika, Sunil Sunil, Peter Simpson, Romina Nabiee, Mathew Moore, Leearne Hinch, Gregory Rice. Enhancing sensitivity and specificity of the CA15-3 (MUC1) breast cancer assay by detection of N-glycolylneuraminic acid (Neu5Gc) using the lectin SubB2M [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB407.