N-glycolylneuraminic acid serum biomarker levels are elevated in breast cancer patients at all stages of disease

Lucy K Shewell; Christopher J Day; Jamie R Kutasovic; Jodie L Abrahams; Jing Wang; Jessica Poole; Colleen Niland; Kaltin Ferguson; Jodi M Saunus; Sunil R Lakhani; Mark von Itzstein; James C Paton; Adrienne W Paton; Michael P Jennings

doi:10.1186/s12885-022-09428-0

N-glycolylneuraminic acid serum biomarker levels are elevated in breast cancer patients at all stages of disease

BMC Cancer. 2022 Mar 26;22(1):334. doi: 10.1186/s12885-022-09428-0.

Authors

Affiliations

¹ Institute for Glycomics, Griffith University, Gold Coast campus, Southport, QLD, 4222, Australia.
² UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Herston, QLD, Australia.
³ Present address: Glycosciences Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
⁴ Pathology Queensland, The Royal Brisbane and Women's Hospital, Herston, QLD, Australia.
⁵ Research Centre for Infectious Diseases, Department of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia.
⁶ Institute for Glycomics, Griffith University, Gold Coast campus, Southport, QLD, 4222, Australia. m.jennings@griffith.edu.au.

^# Contributed equally.

Abstract

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, SubB_A12, 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.

Keywords: Biomarker; Breast cancer; Diagnostic; N-glycolylneuraminic acid; Neu5Gc; Ovarian cancer.

MeSH terms

Biomarkers, Tumor
Breast Neoplasms* / diagnosis
Female
Humans
Neoplasm Recurrence, Local
Neuraminic Acids / metabolism

Substances

Biomarkers, Tumor
Neuraminic Acids
N-glycolylneuraminic acid

Abstract

MeSH terms

Substances

Grants and funding