MSACL 2026 Abstract

Cross-Population Validation of LC–MS Glycoprotein Biomarker Panels for High-Sensitivity Detection of Early-Stage Ovarian Cancer

Michelle M Hill (1), Thomas Stoll (1), Idris Mohd Najib (1), Cheng Siang Lee (2), Thin Thin Aye (2), Adli Bin Ali (3), Fakhrul Syamil Bin Paridul Adras (4), Stefani N Thomas (5), Leo Bolero (1)
(1) Proseek Bio Pty Ltd, Brisbane, Australia; (2) Arcadia Life Sciences, Kuala Lumpur, Malaysia; (3) Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia; (4) Hospital Canselor, Tuanku Muhriz Cheras, Malaysia; (5) University of Minnesota, Minneapolis, MN

Michelle Hill, PhD, BSc (Hon I), BA (Presenter) ProSeek Bio Pty Ltd

Presenter Bio: Michelle Hill, PhD is a biomedical scientist and entrepreneur specializing in clinical proteomics and glycoprotein biomarker translation. She is Founder and CEO of Proseek Bio, developing LC–MS-based clinical blood tests, starting with ovarian cancer presurgical triage. She has authored over 140 publications and is an inventor on multiple diagnostics patents. Michelle previously held research leadership roles, and served as Secretary General of the Human Proteome Organization (HUPO).

Relevant Financial Disclosures (within past 24 months, reported on Apr 20, 2026) Salary Proseek Bio Pty Ltd Ownership Interest Proseek Bio Pty Ltd Discussing Products? NO, presenter will NOT present educational content related to products/services of the ineligible company(ies) listed above. Conflict mitigation NOT REQUIRED.

INTRODUCTION:
Ovarian cancer (OC) remains the most lethal gynecological malignancy, largely due to late diagnosis and the lack of accurate, non-invasive tests to guide pre-surgical decision-making. Current biomarkers have limited sensitivity for early-stage disease and across diverse histological subtypes. Lectin magnetic bead–based mass spectrometry (LeMBA-MS) has previously enabled the discovery of glycoprotein biomarkers associated with high-grade serous ovarian cancer (HGSOC) in United Kingdom (UK) specimens (n=60), with subsequent confirmation in an independent Australian cohort (n=95) [1]. However, validation across additional subtypes and geographically diverse populations is required to support clinical translation.

OBJECTIVES:
To evaluate glycoprotein biomarkers across multiple international cohorts and assess their performance as a high-sensitivity liquid chromatography-mass spectrometry (LC–MS) panel for differentiating early-stage ovarian cancer (across subtypes) from benign conditions.

METHODS:
Previously biobanked serum samples from OC and benign conditions were retrieved from collaborators in Malaysia (n=137), Australia (n=204), and the United States. LeMBA-MS analysis was performed as previously described [1,2], using a scheduled multiple reaction monitoring (MRM) assay measuring 233 peptides. Samples were analyzed within a single laboratory in the country of origin to reflect real-world implementation and assess transferability across sites.

Initial analyses were conducted within individual cohorts to evaluate biomarker performance across OC subtypes and populations prior to pooled modelling.

RESULTS:
Interim analysis of the Malaysian cohort comprised non-HGSOC ovarian cancer subtypes from a multi-ethnic Asian population not represented in prior UK discovery or Australian validation cohorts.
A preliminary biomarker panel demonstrated an AUC of 0.85, with 96% sensitivity and 57% specificity, and showed strong discrimination for Grade II and above disease.

To assess early-stage performance, a subset analysis including benign, Stage I, and Stage II samples was performed. The top-performing panel achieved 100% sensitivity for Stage I–II disease at 61% specificity (AUC = 0.88), demonstrating robust detection of early-stage OC across subtypes.

CONCLUSION:
Initial findings from the Malaysian cohort demonstrate cross-population transferability of glycoprotein biomarkers and support the potential of LC–MS panels for high-sensitivity detection of early-stage ovarian cancer beyond HGSOC. This work represents a key step toward clinically deployable, multi-marker LC-MS assays for pre-surgical triage.

IMPLICATIONS:
High-sensitivity LC–MS panels may enable improved triage of women with suspected ovarian cancer, supporting earlier detection, reducing unnecessary surgery for benign conditions, and improving referral to specialist care. From a laboratory perspective, this study highlights the feasibility of translating multiplex glycoprotein assays into reproducible, cross-site workflows, while underscoring the need for robust QC, standardization, and validation frameworks for multi-marker panels.

Ongoing analysis of Australian and U.S. cohorts will further evaluate robustness and generalizability, informing development of scalable diagnostic panels for routine clinical laboratory implementation.

REFERENCES:
1. Dutt M et al., Discovery and validation of serum glycoprotein biomarkers for high grade serous ovarian cancer. Proteomics Clinical Applications, 2023. 17(4): e2200114.
2. Dutt M. et al., Semi-Automated Lectin Magnetic Bead Array (LeMBA) for Translational Serum Glycoprotein Biomarker Discovery and Validation. Serum/Plasma Proteomics: Methods and Protocols, 2023. 395-411.