PT  - JOURNAL ARTICLE
AU  - Lucy K. Shewell
AU  - Christopher J. Day
AU  - Jamie R. Kutasovic
AU  - Jodie L. Abrahams
AU  - Jing Wang
AU  - Jessica Poole
AU  - Colleen Niland
AU  - Kaltin Ferguson
AU  - Jodi M. Saunus
AU  - Sunil R. Lakhani
AU  - Mark von Itzstein
AU  - James C. Paton
AU  - Adrienne W. Paton
AU  - Michael P Jennings
TI  - <em>N</em>-glycolylneuraminic acid serum biomarker levels are elevated in breast cancer patients at all stages of disease
AID  - 10.1101/2021.06.21.449179
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.06.21.449179
4099  - http://biorxiv.org/content/early/2021/08/03/2021.06.21.449179.short
4100  - http://biorxiv.org/content/early/2021/08/03/2021.06.21.449179.full
AB  - Background Normal human tissues do not express glycans terminating with the sialic acid N-glycolylneuraminic acid (Neu5Gc), yet Neu5Gc-containing glycans have been consistently found in human tumor tissues, cells and secretions and have been proposed as a cancer biomarker. We engineered a Neu5Gc-specific lectin called SubB2M, and previously reported elevated Neu5Gc biomarkers in serum from ovarian cancer patients using a Surface Plasmon Resonance (SPR)-based assay. Here we report an optimized SubB2M SPR-based assay and use this new assay to analyse sera from breast cancer patients for Neu5Gc levels.Methods To enhance specificity of our SPR-based assay, we included a non-sialic acid binding version of SubB, SubBA12, to control for any non-specific binding to SubB2M, which improved discrimination of cancer-free controls from early-stage ovarian cancer. We analysed 96 serum samples from breast cancer patients at all stages of disease compared to 22 cancer-free controls using our optimized SubB2M-A12-SPR assay. We also analysed a collection of serum samples collected at 6 monthly intervals from breast cancer patients at high risk for disease recurrence or spread.Results Analysis of sera from breast cancer cases revealed significantly elevated levels of Neu5Gc biomarkers at all stages of breast cancer. We show that Neu5Gc serum biomarker levels can discriminate breast cancer patients from cancer-free individuals with 98.96% sensitivity and 100% specificity. Analysis of serum collected prospectively, post-diagnosis, from breast cancer patients at high risk for disease recurrence showed a trend for a decrease in Neu5Gc levels immediately following treatment for those in remission.Conclusions Neu5Gc serum biomarkers are a promising new tool for early detection and disease monitoring for breast cancer that may complement current imaging- and biopsy-based approaches.Competing Interest StatementThe following authors (JCP, AWP, CJD and MPJ) declare that they are named inventors on a patent on the SubB2M technology (WO2018085888A1) and a second patent (JCP, AWP, CJD, LKS and MPJ) for improvements to the SubB2M test (2021901444). Both of these patents were licensed to BARD1 Life Sciences, VIC, Australia in 2020.