Novel Diagnostic Biomarkers for High-Grade Serous Ovarian Cancer Uncovered by Data-Independent Acquisition Mass Spectrometry

Sunghyun Huh, Chaewon Kang, Ji Eun Park, Dowoon Nam, Se Ik Kim, Aeran Seol, Kyerim Choi, Daehee Hwang, Myeong Hee Yu, Hyun Hoon Chung, Sang Won Lee, Un Beom Kang

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

High-grade serous ovarian cancer (HGSOC) represents the major histological type of ovarian cancer, and the lack of effective screening tools and early detection methods significantly contributes to the poor prognosis of HGSOC. Currently, there are no reliable diagnostic biomarkers for HGSOC. In this study, we performed liquid chromatography data-independent acquisition tandem mass spectrometry (MS) on depleted serum samples from 26 HGSOC cases and 24 healthy controls (HCs) to discover potential HGSOC diagnostic biomarkers. A total of 1,847 proteins were identified across all samples, among which 116 proteins showed differential expressions between HGSOC patients and HCs. Network modeling showed activations of coagulation and complement cascades, platelet activation and aggregation, neutrophil extracellular trap formation, toll-like receptor 4, insulin-like growth factor, and transforming growth factor β signaling, as well as suppression of lipoprotein assembly and Fc gamma receptor activation in HGSOC. Based on the network model, we prioritized 28 biomarker candidates and validated 18 of them using targeted MS assays in an independent cohort. Predictive modeling showed a sensitivity of 1 and a specificity of 0.91 in the validation cohort. Finally, in vitro functional assays on four potential biomarkers (FGA, VWF, ARHGDIB, and SERPINF2) suggested that they may play an important role in cancer cell proliferation and migration in HGSOC. All raw data were deposited in PRIDE (PXD033169).

Original languageEnglish
JournalJournal of Proteome Research
DOIs
Publication statusAccepted/In press - 2022

Bibliographical note

Funding Information:
This work was supported in part by the Bertis Inc. and the Korea Basic Science Institute (KBSI) National Research Facilities and Equipment Center (NFEC) funded by the Korean government (Ministry of Education) (2019R1A6C1010028).

Publisher Copyright:
© 2022 American Chemical Society.

Keywords

  • Data-independent acquisition
  • High-grade serous ovarian cancer
  • Mass spectrometry
  • Proteomics
  • Serum biomarker

ASJC Scopus subject areas

  • General Chemistry
  • Biochemistry

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