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Article

Proteomic Discovery of Biomarkers to Predict Prognosis of High-Grade Serous Ovarian Carcinoma

1
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul 03080, Korea
2
Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Korea
3
Proteomics Core Facility, Biomedical Research Institute, Seoul National University Hospital, Seoul 03082, Korea
4
Center for Precision Medicine, Seoul National University Hospital, Seoul 03080, Korea
*
Authors to whom correspondence should be addressed.
These two authors contributed equally as first authors.
Cancers 2020, 12(4), 790; https://doi.org/10.3390/cancers12040790
Received: 30 January 2020 / Revised: 21 March 2020 / Accepted: 24 March 2020 / Published: 26 March 2020
(This article belongs to the Special Issue The Cancer Proteome)
Initial identification of biomarkers predicting the exact prognosis of high-grade serous ovarian carcinoma (HGSOC) is important in precision cancer medicine. This study aimed to investigate prognostic biomarkers of HGSOC through proteomic analysis. We conducted label-free liquid chromatography-mass spectrometry using chemotherapy-naïve, fresh-frozen primary HGSOC specimens, and compared the results between a favorable prognosis group (progression-free survival (PFS) ≥ 18 months, n = 6) and a poor prognosis group (PFS < 18 months, n = 6). Among 658 differentially expressed proteins, 288 proteins were upregulated in the favorable prognosis group and 370 proteins were upregulated in the poor prognosis group. Using hierarchical clustering, we selected α1-antitrypsin (AAT), nuclear factor-κB (NFKB), phosphomevalonate kinase (PMVK), vascular adhesion protein 1 (VAP1), fatty acid-binding protein 4 (FABP4), platelet factor 4 (PF4), apolipoprotein A1 (APOA1), and α1-acid glycoprotein (AGP) for further validation via immunohistochemical (IHC) staining in an independent set of chemotherapy-naïve primary HGSOC samples (n = 107). Survival analyses revealed that high expression of AAT, NFKB, and PMVK were independent biomarkers for favorable PFS. Conversely, high expression of VAP1, FABP4, and PF4 were identified as independent biomarkers for poor PFS. Furthermore, we constructed models predicting the 18-month PFS by combining clinical variables and IHC results. Through leave-one-out cross-validation, the optimal model was based on initial serum CA-125, germline BRCA1/2 mutations, residual tumors after surgery, International Federation of Gynecology and Obstetrics (FIGO) stage, and expression levels of the six proteins. The present results elucidate the proteomic landscape of HGSOC and six protein biomarkers to predict the prognosis of HGSOC. View Full-Text
Keywords: ovarian neoplasms; high-grade serous carcinoma; proteomics; immunohistochemistry; prognosis ovarian neoplasms; high-grade serous carcinoma; proteomics; immunohistochemistry; prognosis
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MDPI and ACS Style

Kim, S.I.; Jung, M.; Dan, K.; Lee, S.; Lee, C.; Kim, H.S.; Chung, H.H.; Kim, J.-W.; Park, N.H.; Song, Y.-S.; Han, D.; Lee, M. Proteomic Discovery of Biomarkers to Predict Prognosis of High-Grade Serous Ovarian Carcinoma. Cancers 2020, 12, 790. https://doi.org/10.3390/cancers12040790

AMA Style

Kim SI, Jung M, Dan K, Lee S, Lee C, Kim HS, Chung HH, Kim J-W, Park NH, Song Y-S, Han D, Lee M. Proteomic Discovery of Biomarkers to Predict Prognosis of High-Grade Serous Ovarian Carcinoma. Cancers. 2020; 12(4):790. https://doi.org/10.3390/cancers12040790

Chicago/Turabian Style

Kim, Se I., Minsun Jung, Kisoon Dan, Sungyoung Lee, Cheol Lee, Hee S. Kim, Hyun H. Chung, Jae-Weon Kim, Noh H. Park, Yong-Sang Song, Dohyun Han, and Maria Lee. 2020. "Proteomic Discovery of Biomarkers to Predict Prognosis of High-Grade Serous Ovarian Carcinoma" Cancers 12, no. 4: 790. https://doi.org/10.3390/cancers12040790

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