Novel proteomic technologies to address gaps in pre-clinical ovarian cancer biomarker discovery efforts

ABSTRACT

Introduction

An estimated 20,000 women in the United States will receive a diagnosis of ovarian cancer in 2023. Late-stage diagnosis is associated with poor prognosis. There is a need for novel diagnostic biomarkers for ovarian cancer to improve early-stage detection and novel prognostic biomarkers to improve patient treatment.

Areas covered

This review provides an overview of the clinicopathological features of ovarian cancer and the currently available biomarkers and treatment options. Two affinity-based platforms using proximity extension assays (Olink) and DNA aptamers (SomaLogic) are described in the context of highly reproducible and sensitive multiplexed assays for biomarker discovery. Recent developments in ion mobility spectrometry are presented as novel techniques to apply to the biomarker discovery pipeline. Examples are provided of how these aforementioned methods are being applied to biomarker discovery efforts in various diseases, including ovarian cancer.

Expert opinion

Translating novel ovarian cancer biomarkers from candidates in the discovery phase to bona fide biomarkers with regulatory approval will have significant benefits for patients. Multiplexed affinity-based assay platforms and novel mass spectrometry methods are capable of quantifying low abundance proteins to aid biomarker discovery efforts by enabling the robust analytical interrogation of the ovarian cancer proteome.

KEYWORDS:

• Ovarian cancer
• proteomics
• mass spectrometry
• biomarkers
• ion mobility spectrometry

Article highlights

• The fifth highest cause of cancer mortality in the US is ovarian cancer. The disease has a poor prognosis, is often diagnosed at later more severe stages, and has high rates of recurrence.

• This review provides an overview of the clinicopathological features of ovarian cancer and the currently available biomarkers and treatment options.

• Diagnostic biomarkers with high sensitivity and specificity are of critical importance in the setting of ovarian cancer to improve early detection of the disease, consequently improving disease prognosis.

• Two multiplexed, high-throughput affinity-based proteomic techniques, Olink (proximity extension assays) and SomaScan (DNA aptamer assays), have the potential to accelerate biomarker discovery efforts for ovarian cancer.

• Ion mobility spectrometry is poised to facilitate novel biomarker discovery efforts due to its ability to improve the accurate localization of disease-specific protein post-translational modifications.

• The most promising advances in biomarker translation will likely be in the form of multi-biomarker panels.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

HA Jordan and SN Thomas drafted and wrote the manuscript.

Acknowledgments

The authors would like to thank the members of the Thomas lab for helpful discussions regarding the content of the manuscript.

Ethical statements

This manuscript does not involve any clinical studies or human subjects research.

Additional information

Funding

HA Jordan received funding from the United Kingdom Medical Research Council Transition Fund (#MR/N013913/1). SN Thomas acknowledges funding provided by the Minnesota Ovarian Cancer Alliance and the Department of Laboratory Medicine and Pathology of the University of Minnesota.