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

作     者：Yang, Ju Dong Sun, Zhifu Hu, Chunling Lai, Jinping Dove, Rebecca Nakamura, Ikuo Lee, Ju-Seog Thorgeirsson, Snorri S. Kang, Koo Jeong Chu, In-Sun Roberts, Lewis R. 

作者机构：Mayo Clin Miles Shirley Fiterman Ctr Digest Dis Coll Med Rochester MN 55905 USA Mayo Clin Ctr Canc Rochester MN 55905 USA Mayo Clin Dept Biomed Stat & Informat Coll Med Rochester MN 55905 USA Univ Texas MD Anderson Canc Ctr Dept Syst Biol Houston TX 77030 USA NCI Expt Carcinogenesis Lab Bethesda MD 20892 USA Keimyung Univ Sch Med Taegu South Korea Korea Res Inst Biosci & Biotechnol Korean Bioinformat Ctr Taejon South Korea 

出 版 物：《GENES CHROMOSOMES & CANCER》 (基因、染色体和癌)

年 卷 期：2011年第50卷第2期

页      面：122-135页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：National Institutes of Health [CA100882, CA128633] Mayo Clinic Center for Cell Signaling in Gastroenterology [NIDDK P30DK084567] Mayo Clinic Cancer Center Mayo Foundation 21C Frontier Functional Human Genome Project [MEST FG-4-2] KRIBB 

主　　题：Association (Psychology) Cell Adhesion signalling network Hepatocarcinogenesis TGFB1 gene Survival Hepatocellular Cancer HNF4A gene SULF2 gene Signal Pathways Neoplastic Processes Human-centered computing SULF1 gene 

摘      要：The heparin-degrading endosulfatases sulfatase 1 (SULF1) and sulfatase 2 (SULF2) have opposing effects in hepatocarcinogenesis 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 phenotype 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/beta-catenin and epithelial mesenchymal transition signaling pathways. Genes uniquely correlated with SULF2 were more associated with neoplastic processes than genes uniquely correlated 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 associations 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. (C) 2010 Wiley-Liss, Inc.