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Epigenetic loss of heparan sulfate 3-O-sulfation sensitizes ovarian carcinoma to oncogenic signals and predicts prognosis

Lookup NU author(s): Dr Wei-Yu Lin

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This is the final published version of an article that has been published in its final definitive form by Wiley-Liss Inc., 2018.

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Abstract

© 2018 UICC Precision medicine requires markers for therapeutic guidance. The purpose of this study was to determine whether epithelial ovarian cancer (EOC) epigenetics can lead to the identification of biomarkers for precision medicine. Through integrative methylomics, we discovered and validated the epigenetic signature of NEFH and HS3ST2 as an independent prognostic factor for type II EOC in our dataset (n = 84), and two independent methylomics datasets (total n = 467). Integrated transcriptomics dataset (n = 1147) and tissue microarrays (n = 54) of HS3ST2 also related to high-methylation statuses and the EOC prognosis. Mechanistic explorations of HS3ST2 have assessed responses to oncogenic stimulations such as IL-6, EGF, and FGF2 in cancer cells. The combination of HS3ST2 and various oncogenic ligands also confers the worse outcome. 3-O-sulfation of heparan sulfate by HS3ST2 makes ovarian cancer cells intrinsically sensitive to oncogenic signals, which sheds new light on the application of HS3ST2 as a companion diagnostic for targeted therapy using kinase inhibitors or therapeutic antibodies.


Publication metadata

Author(s): Huang R-L, Chen H-J, Chen L-Y, Chao T-K, Lin W-Y, Liew P-L, Su P-H, Weng Y-C, Wang Y-C, Liao C-C, Hsu Y-W, Wang H-C, Lai H-C

Publication type: Article

Publication status: Published

Journal: International Journal of Cancer

Year: 2018

Volume: 143

Issue: 8

Pages: 1943-1953

Print publication date: 15/10/2018

Online publication date: 07/05/2018

Acceptance date: 23/04/2018

Date deposited: 01/10/2018

ISSN (print): 0020-7136

ISSN (electronic): 1097-0215

Publisher: Wiley-Liss Inc.

URL: https://doi.org/10.1002/ijc.31580

DOI: 10.1002/ijc.31580


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