@article{61a350f0febd45899416c979b5064ef6,
title = "Epigenetic loss of heparan sulfate 3-O-sulfation sensitizes ovarian carcinoma to oncogenic signals and predicts prognosis",
abstract = "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.",
keywords = "DNA methylation, epithelial ovarian cancer, heparan sulfation, HS3ST2, prognosis, targeted therapy",
author = "Huang, {Rui Lan} and Chen, {Hsiang Ju} and Chen, {Lin Yu} and Chao, {Tai Kuang} and Lin, {Wei Yu} and Liew, {Phui Ly} and Su, {Po Hsuan} and Weng, {Yu Chun} and Wang, {Yu Chi} and Liao, {Chi Chun} and Hsu, {Yaw Wen} and Wang, {Hui Chen} and Lai, {Hung Cheng}",
note = "Funding Information: We thank Tien-Shuo Huang for technical support. Conflict of interest: The authors declare no competing financial interests. Author Contributions: R.L.H. performed clinical experiments, wrote the manuscript and analyzed data. H.J.C. planned and performed the experiments for in vitro studies. L.Y.C. helped with in vitro studies. Y.W.H. helped with discussion and western blotting experiments. T.K.C. and P.L.L. performed and managed the histopathological and immunochemical analysis. W.Y.L. helped with the data analysis. P.H.S. helped with in vitro studies design. Yu-Chun W. helped with in vitro studies. Yu-Chi W. and C.C.L. reviewed the clinical evaluations. H.C.W. helped with DNA preparation and bisulfite pyrosequencing. H.C.L. initiated the study, formulated the hypothesis and wrote the manuscript. Publisher Copyright: {\textcopyright} 2018 UICC",
year = "2018",
month = oct,
day = "15",
doi = "10.1002/ijc.31580",
language = "English",
volume = "143",
pages = "1943--1953",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "John Wiley and Sons Inc.",
number = "8",
}
