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Sulfatase 1 and Sulfatase 2 in Hepatocellular Carcinoma: Associated Signaling Pathways, Tumor Phenotypes, and Survival

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Author(s)
Ju Dong YangZhifu SunChunling HuJinping LaiRebecca DoveIkuo NakamuraJu-Seog LeeSnorri S. ThorgeirssonKoo Jeong KangIn-Sun ChuLewis R. Roberts
Keimyung Author(s)
Kang, Koo Jeong
Department
Dept. of Surgery (외과학)
Journal Title
Genes, Chromosomes and Cancer
Issued Date
2011
Volume
50
Issue
2
Abstract
The heparin-degrading endosulfatases sulfatase 1 (SULF1) and sulfatase 2 (SULF2) have opposing effects in hepatocarcino-
genesis despite structural similarity. Using mRNA expression arrays, we analyzed the correlations of SULF expression with
signaling networks in human hepatocellular carcinomas (HCCs) and the associations of SULF expression with tumor phe-
notype and patient survival. Data from two mRNA microarray analyses of 139 and 36 HCCs and adjacent tissues were
used as training and validation sets. Partek and Metacore software were used to identify SULF correlated genes and their
associated signaling pathways. Associations between SULF expression, the hepatoblast subtype of HCC, and survival were
examined. Both SULF1 and 2 had strong positive correlations with periostin, IQGAP1, TGFB1, and vimentin and inverse
correlations with HNF4A and IQGAP2. Genes correlated with both SULFs were highly associated with the cell adhesion,
cytoskeletal remodeling, blood coagulation, TGFB, and Wnt/b-catenin and epithelial mesenchymal transition signaling path-
ways. Genes uniquely correlated with SULF2 were more associated with neoplastic processes than genes uniquely corre-
lated with SULF1. High SULF expression was associated with the hepatoblast subtype of HCC. There was a bimodal effect
of SULF1 expression on prognosis, with patients in the lowest or highest tertile having a worse prognosis than those in
the middle tertile. SULFs have complex effects on HCC signaling and patient survival. There are functionally similar associ-
ations with cell adhesion, ECM remodeling, TGFB, and WNT pathways, but also unique associations of SULF1 and SULF2.
The roles and targeting of the SULFs in cancer require further investigation
Keimyung Author(s)(Kor)
강구정
Publisher
School of Medicine
Citation
Ju Dong Yang et al. (2011). Sulfatase 1 and Sulfatase 2 in Hepatocellular
Carcinoma: Associated Signaling Pathways, Tumor
Phenotypes, and Survival. Genes, Chromosomes and Cancer, 50(2), 122–135. doi: 10.1002/gcc.20838
Type
Article
ISSN
1045-2257
DOI
10.1002/gcc.20838
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35774
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Surgery (외과학)
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