Proteomics

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Discovery and validation of serum glycoprotein biomarker panel for detection of high grade serous ovarian cancer


ABSTRACT: We aimed to discover and validate a panel of serum biomarkers for high grade serous ovarian cancer (HGSOC) using our lectin-magnetic bead array-coupled proteomics platform. Serum from age-matched women with HGSOC, benign tumours or healthy controls were analysed in discovery (UKCTOCS, n=30 and UKOPS, n=30) and validation (Australian Ovarian Cancer Study, n=95) cohorts using shotgun and targeted proteomics, respectively. A 7-lectin discovery screen shortlisted 60 candidate proteins and 3 lectins for validation, which revealed elevated levels of AAL, SNA or STL-binding FIBB, CO9, ITIH3, HPT, A1AT, AACT in HGSOC, while IBP3, A2MG, PON1, CHLE and ALS were reduced. Multimarker panels were developed using generalized regression with lasso estimation and leave-one-out cross-validation. The best performing panel comprised of 13 peptides from Solanum Tuberosum lectin (STL)-binding proteins with 96.3% area under the receiver operating curve, 97.7% specificity and 78.6% sensitivity for distinguishing HGSOC from benign and healthy groups. The peptides robust in cross-validations were from IBP3, KNG1, CO9, THRB, HPTR, HPT, FINC, FA10, GELS. The validated serum biomarkers show promise for early detection of HGSOC and should be further evaluated.

ORGANISM(S): Homo Sapiens

SUBMITTER: Mriga Dutt  

PROVIDER: PXD033108 | panorama | Tue Aug 06 00:00:00 BST 2024

REPOSITORIES: PanoramaPublic

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Discovery and validation of serum glycoprotein biomarkers for high grade serous ovarian cancer.

Dutt Mriga M   Hartel Gunter G   Richards Renee S RS   Shah Alok K AK   Mohamed Ahmed A   Apostolidou Sophia S   Gentry-Maharaj Aleksandra A   Hooper John D JD   Perrin Lewis C LC   Menon Usha U   Hill Michelle M MM  

Proteomics. Clinical applications 20230601 4


<h4>Purpose</h4>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.<h4>Experimental design</h4>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 p  ...[more]

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