E-Poster Presentation 33rd Lorne Cancer Conference 2021

An engineered lectin, SubB2M, can detect N-glycolylneuraminic acid biomarkers in sera from breast cancer patients (#198)

Lucy K Shewell 1 , Jamie R Kutasovic 2 , Jodie L Abrahams 1 , Jackie Wang 1 , Colleen Niland 2 , Kaltin Ferguson 2 , Jodi M Saunus 2 , Sunil R Lakhani 2 3 , James C Paton 4 , Adrienne W Paton 4 , Christopher J Day 1 , Michael P Jennings 1
  1. Institute for Glycomics, Griffith University, GOLD COAST, QLD, Australia
  2. UQ Centre for Clinical Research, The University of Queensland, Herston, QLD, Australia
  3. Pathology Queensland, The Royal Brisbane and Women’s Hospital, Herston, QLD, Australia
  4. Research Centre for Infectious Diseases, University of Adelaide, Adelaide, SA, Australia

Background

N-glycolylneuraminic acid (Neu5Gc) is an aberrant glycosylation found in human tumour cells and has been proposed as a cancer biomarker. Until our recent work, no progress has been made towards the development of a Neu5Gc biomarker-based assay for cancer detection and monitoring. Using our purpose-engineered Neu5Gc-specific, lectin, SubB2M, we detected elevated Neu5Gc in sera from ovarian cancer patients. Here we use SubB2M to detect Neu5Gc tumour biomarkers in sera from breast cancer patients.

Methods

Using a surface plasmon resonance (SPR)-based assay with SubB2M for detection, we analyzed serum samples from 96 patients with Stage I - IV breast cancer, as well as 22 cancer-free controls. In addition, we analyzed serum samples from a cohort of patients with high-risk breast cancer collected prospectively over time.

Results

Significantly elevated mean levels of Neu5Gc glycans were detected in serum from patients with all stages of breast cancer compared to cancer-free controls (P value = <0.0001 for all stages). Receiver operating characteristic analyses showed that serum Neu5Gc levels can discriminate Stage I patients from cancer-free individuals with 95.83% sensitivity and 100% specificity, while Stage II, Stage III and Stage IV patients can be distinguished from cancer-free individuals with 100% sensitivity and 100% specificity. Analysis of a series of serum samples collected prospectively, post-diagnosis from a cohort of high-risk breast cancer patients showed a trend for a decrease in Neu5Gc levels immediately following treatment.

Conclusions

Detection of Neu5Gc-glycans using SubB2M may be useful for early detection of breast cancer and as a tool for monitoring treatment and progression in late stage disease.

Impact

A blood-based biomarker test for early detection and accurate monitoring of disease progression in breast cancer would drastically improve patient outcomes.