title: IGFBP7 downregulation is associated with tumor progression and clinical outcome in hepatocellular carcinoma.
abstract: Insulin-like growth factor-binding protein 7 (IGFBP7) functions in several cellular processes including proliferation, senescence and apoptosis. This study analyzed IGFBP7 function in hepatocellular carcinoma (HCC) cells by gene manipulation and investigated the prognostic significance of IGFBP7 expression in clinical HCC samples. In this study, we investigated changes in malignant potential such as cell growth and invasiveness in an HCC cell line, PLC/PRF/5, after transfection with shRNA against IGFBP7. The extent of apoptosis and cell cycle progression were examined after the transfection. The correlation between immunohistochemically determined IGFBP7 expression and long-term postoperative prognosis after curative resection was also investigated in clinical HCC specimens obtained from 104 patients. PLC/PRF/5 cells transfected with shRNA against IGFBP7 showed significantly more rapid growth and stronger invasiveness than control cells. Annexin V assays showed that the IGFBP7-depleted cells were significantly more resistant to apoptosis than the control cells, and showed decreased expression of cleaved caspase-3 and PARP. Cell cycle progression was more rapid in the IGFBP7-suppressed cells. In clinical HCC specimens, IGFBP7 expression was judged as positive in 67 patients (64.4%) and negative in the remaining 37 patients (35.6%). The IGFBP7 downregulation correlated significantly with poor postoperative prognosis, and IGFBP7 status was identified as an independent significant prognostic factor. Our results indicated that IGFBP7 expression correlated significantly with the malignant potential in HCC cells, suggesting that the expression could be a useful prognostic marker for HCC.
authors.affiliation: Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Tomimaru
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Eguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wada
authors.forename: Shogo
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Marubashi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tanemura
authors.forename: Koji
authors.initials: K
authors.lastname: Umeshita
authors.forename: Tonsok
authors.initials: T
authors.lastname: Kim
authors.forename: Kenichi
authors.initials: K
authors.lastname: Wakasa
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nagano
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D018450:Disease Progression; D015536:Down-Regulation; D006801:Humans; D007150:Immunohistochemistry; D018969:Insulin-Like Growth Factor Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D014162:Transfection
chemical_list: D018969:Insulin-Like Growth Factor Binding Proteins; C102529:insulin-like growth factor binding protein-related protein 1