Mapping Epitopes Recognised by Autoantibodies Shows Potential for the Diagnosis of High-Grade Serous Ovarian Cancer and Monitoring Response to Therapy for This Malignancy
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 p...
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| Format: | Article |
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MDPI AG
2021-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/16/4201 |
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| author | Rhiane Moody Kirsty Wilson Nirmala Chandralega Kampan Orla M. McNally Thomas W. Jobling Anthony Jaworowski Andrew N. Stephens Magdalena Plebanski |
| author_facet | Rhiane Moody Kirsty Wilson Nirmala Chandralega Kampan Orla M. McNally Thomas W. Jobling Anthony Jaworowski Andrew N. Stephens Magdalena Plebanski |
| author_sort | Rhiane Moody |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T08:56:44Z |
| format | Article |
| id | doaj.art-a60410754c1f405cbd751c249e9fcdc7 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T08:56:44Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-a60410754c1f405cbd751c249e9fcdc72023-11-22T07:05:18ZengMDPI AGCancers2072-66942021-08-011316420110.3390/cancers13164201Mapping Epitopes Recognised by Autoantibodies Shows Potential for the Diagnosis of High-Grade Serous Ovarian Cancer and Monitoring Response to Therapy for This MalignancyRhiane Moody0Kirsty Wilson1Nirmala Chandralega Kampan2Orla M. McNally3Thomas W. Jobling4Anthony Jaworowski5Andrew N. Stephens6Magdalena Plebanski7School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, AustraliaSchool of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, AustraliaDepartment of Obstetrics and Gynaecology, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur 56000, MalaysiaGynaeoncology Unit, Royal Women’s Hospital, Parkville, VIC 3052, AustraliaDepartment of Gynaecological Oncology, Monash Medical Centre, Bentleigh East, VIC 3165, AustraliaSchool of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, AustraliaHudson Institute of Medical Research, Clayton, VIC 3168, AustraliaSchool of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, AustraliaAutoantibodies 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.https://www.mdpi.com/2072-6694/13/16/4201HSF1epitope mappingovarian cancer peptidesIgAbiomarkers |
| spellingShingle | Rhiane Moody Kirsty Wilson Nirmala Chandralega Kampan Orla M. McNally Thomas W. Jobling Anthony Jaworowski Andrew N. Stephens Magdalena Plebanski Mapping Epitopes Recognised by Autoantibodies Shows Potential for the Diagnosis of High-Grade Serous Ovarian Cancer and Monitoring Response to Therapy for This Malignancy Cancers HSF1 epitope mapping ovarian cancer peptides IgA biomarkers |
| title | Mapping Epitopes Recognised by Autoantibodies Shows Potential for the Diagnosis of High-Grade Serous Ovarian Cancer and Monitoring Response to Therapy for This Malignancy |
| title_full | Mapping Epitopes Recognised by Autoantibodies Shows Potential for the Diagnosis of High-Grade Serous Ovarian Cancer and Monitoring Response to Therapy for This Malignancy |
| title_fullStr | Mapping Epitopes Recognised by Autoantibodies Shows Potential for the Diagnosis of High-Grade Serous Ovarian Cancer and Monitoring Response to Therapy for This Malignancy |
| title_full_unstemmed | Mapping Epitopes Recognised by Autoantibodies Shows Potential for the Diagnosis of High-Grade Serous Ovarian Cancer and Monitoring Response to Therapy for This Malignancy |
| title_short | Mapping Epitopes Recognised by Autoantibodies Shows Potential for the Diagnosis of High-Grade Serous Ovarian Cancer and Monitoring Response to Therapy for This Malignancy |
| title_sort | mapping epitopes recognised by autoantibodies shows potential for the diagnosis of high grade serous ovarian cancer and monitoring response to therapy for this malignancy |
| topic | HSF1 epitope mapping ovarian cancer peptides IgA biomarkers |
| url | https://www.mdpi.com/2072-6694/13/16/4201 |
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