title: Clinical and biological significance of hepatoma-derived growth factor in Ewing's sarcoma.
abstract: We sought to investigate the clinicopathological significance and biological function of hepatoma-derived growth factor (HDGF) in Ewing's sarcoma. Our results showed that HDGF expression is up-regulated in Ewing's sarcoma. Nuclear HDGF expression is significantly associated with tumour volume (p < 0.001), metastases at diagnosis (p < 0.001), low overall survival rate (p < 0.001) and low disease-free survival rate (p < 0.001). HDGF knock-down results in significant reduction of Ewing's sarcoma cell growth, proliferation and enhances tumourigenesis, both in vitro and in vivo. Meanwhile, HDGF knock-down causes cell cycle arrest and enhanced sensitization to serum starvation-induced apoptosis. Furthermore, recombinant HDGF promotes proliferation and colony formation of Ewing's sarcoma cells. Ninety-eight candidate HDGF downstream genes were identified in Ewing's sarcoma cells using cDNA microarray analysis. In addition, we found that HDGF knock-down inhibited FLI1 expression in Ewing's sarcoma cells at the mRNA and protein levels. Our findings suggest that HDGF exhibits oncogenic properties and may be a novel prognostic factor in Ewing's sarcoma. Targeting HDGF might be a potential therapeutic strategy for Ewing's sarcoma.
authors.affiliation: Department of Pathology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Fenfen
authors.initials: F
authors.lastname: Zhang
authors.forename: Huijuan
authors.initials: H
authors.lastname: Shi
authors.forename: Tiantian
authors.initials: T
authors.lastname: Zhen
authors.forename: Sujuan
authors.initials: S
authors.lastname: Dai
authors.forename: Lili
authors.initials: L
authors.lastname: Kang
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Liang
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.forename: Anjia
authors.initials: A
authors.lastname: Han
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D034622:RNA Interference; D012512:Sarcoma, Ewing / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D036341:Intercellular Signaling Peptides and Proteins; C051610:hepatoma-derived growth factor
keywords: Ewing's sarcoma; biological significance; clinicopathology; hepatoma-derived growth factor