| Title: |
Discovery and validation of serum glycoprotein biomarkers for high grade serous ovarian cancer |
| Authors: |
Dutt, Mriga; Hartel, Gunter; Richards, Renee S; Shah, Alok K; Mohamed, Ahmed; Apostolidou, Sophia; Gentry-Maharaj, Aleksandra; Australian Ovarian Cancer Study Group, .; Hooper, John D; Perrin, Lewis C; Menon, Usha; Hill, Michelle M |
| Source: |
Proteomics: Clinical Applications , Article 2200114. (2023) (In press). |
| Publisher Information: |
Wiley |
| Publication Year: |
2023 |
| Collection: |
University College London: UCL Discovery |
| Subject Terms: |
high grade serous ovarian cancer; lectin magnetic bead array (LeMBA); mass spectrometry; ovarian cancer screening; serum glycoprotein biomarker |
| Description: |
Purpose: This study aimed to identify serum glycoprotein biomarkers for early detection of high-grade serous ovarian cancer (HGSOC), the most common and aggressive histotype of ovarian cancer./ Experimental design: The glycoproteomics pipeline lectin magnetic bead array (LeMBA)-mass spectrometry (MS) was used in age-matched case-control serum samples. Clinical samples collected at diagnosis were divided into discovery (n = 30) and validation (n = 98) sets. We also analysed a set of preclinical sera (n = 30) collected prior to HGSOC diagnosis in the UK Collaborative Trial of Ovarian Cancer Screening./ Results: A 7-lectin LeMBA-MS/MS discovery screen shortlisted 59 candidate proteins and three lectins. Validation analysis using 3-lectin LeMBA-multiple reaction monitoring (MRM) confirmed elevated A1AT, AACT, CO9, HPT and ITIH3 and reduced A2MG, ALS, IBP3 and PON1 glycoforms in HGSOC. The best performing multimarker signature had 87.7% area under the receiver operating curve, 90.7% specificity and 70.4% sensitivity for distinguishing HGSOC from benign and healthy groups. In the preclinical set, CO9, ITIH3 and A2MG glycoforms were altered in samples collected 11.1 ± 5.1 months prior to HGSOC diagnosis, suggesting potential for early detection./ Conclusions and clinical relevance: Our findings provide evidence of candidate early HGSOC serum glycoprotein biomarkers, laying the foundation for further study in larger cohorts. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10171913/1/Discovery%20and%20validation%20of%20serum%20glycoprotein%20biomarkers%20for%20high%20grade%20serous.pdf; https://discovery.ucl.ac.uk/id/eprint/10171913/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10171913/1/Discovery%20and%20validation%20of%20serum%20glycoprotein%20biomarkers%20for%20high%20grade%20serous.pdf; https://discovery.ucl.ac.uk/id/eprint/10171913/ |
| Rights: |
open |
| Accession Number: |
edsbas.10DE840F |
| Database: |
BASE |