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.

Serum samples from healthy, benign and HGSOC patients.