Mapping Epitopes Recognised by Autoantibodies Shows Potential for the Diagnosis of High-Grade Serous Ovarian Cancer and Monitoring Response to Therapy for This Malignancy

• Published in: Cancers Vol. 13; no. 16; p. 4201
• Main Authors: Moody, Rhiane, Wilson, Kirsty, Kampan, Nirmala Chandralega, McNally, Orla M., Jobling, Thomas W., Jaworowski, Anthony, Stephens, Andrew N., Plebanski, Magdalena
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 20.08.2021; MDPI
• Subjects: Antibodies; Autoantibodies; Autoimmunity; Biomarkers; Cancer therapies; Chemotherapy; Clinical trials; Correlation analysis; Diagnosis; Disease; Enzyme-linked immunosorbent assay; Epitope mapping; Gynecology; Heat shock factors; Heat shock proteins; HSF1 protein; Immunoglobulin A; Lymphocytes B; Malignancy; Medical prognosis; Metastasis; Ovarian cancer; Patients; Peptides; Phosphorylation; Proteins; Surgery; Womens health; United States > US
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers13164201

Autoantibodies recognising phosphorylated heat shock factor 1 (HSF1-PO4) protein are suggested as potential new diagnostic biomarkers for early-stage high-grade serous ovarian cancer (HGSOC). We predicted in silico B-cell epitopes in human and murine HSF1. Three epitope regions were synthesised as peptides. Circulating immunoglobulin A (cIgA) against the predicted peptide epitopes or HSF1-PO4 was measured using ELISA, across two small human clinical trials of HGSOC patients at diagnosis. To determine whether chemotherapy would promote changes in reactivity to either HSF1-PO4 or the HSF-1 peptide epitopes, IgA responses were further assessed in a sample of patients after a full cycle of chemotherapy. Anti-HSF1-PO4 responses correlated with antibody responses to the three selected epitope regions, regardless of phosphorylation, with substantial cross-recognition of the corresponding human and murine peptide epitope variants. Assessing reactivity to individual peptide epitopes, compared to HSF1-PO4, improved assay sensitivity. IgA responses to HSF1-PO4 further increased significantly post treatment, indicating that HSF1-PO4 is a target for immunity in response to chemotherapy. Although performed in a small cohort, these results offer potential insights into the interplay between autoimmunity and ovarian cancer and offer new peptide biomarkers for early-stage HGSOC diagnosis, to monitor responses to chemotherapy, and widely for pre-clinical HGSOC research.