IGFBP7 downregulation is associated with tumor progression and clinical outcome in hepatocellular carcinoma

Yoshito Tomimaru, Hidetoshi Eguchi, Hiroshi Wada, Shogo Kobayashi, Shigeru Marubashi, Masahiro Tanemura, Koji Umeshita, Tonsok Kim, Kenichi Wakasa, Yuichiro Doki, Masaki Mori, Hiroaki Nagano

Research output: Contribution to journalArticle

31 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)319-327
Number of pages9
JournalInternational Journal of Cancer
Volume130
Issue number2
DOIs
Publication statusPublished - Jan 15 2012

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Hepatocellular Carcinoma
Down-Regulation
Neoplasms
Apoptosis
Small Interfering RNA
Transfection
insulin-like growth factor binding protein-related protein 1
Cell Cycle
Annexin A5
Growth
Caspase 3
Cell Line

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Tomimaru, Y., Eguchi, H., Wada, H., Kobayashi, S., Marubashi, S., Tanemura, M., ... Nagano, H. (2012). IGFBP7 downregulation is associated with tumor progression and clinical outcome in hepatocellular carcinoma. International Journal of Cancer, 130(2), 319-327. https://doi.org/10.1002/ijc.25994

IGFBP7 downregulation is associated with tumor progression and clinical outcome in hepatocellular carcinoma. / Tomimaru, Yoshito; Eguchi, Hidetoshi; Wada, Hiroshi; Kobayashi, Shogo; Marubashi, Shigeru; Tanemura, Masahiro; Umeshita, Koji; Kim, Tonsok; Wakasa, Kenichi; Doki, Yuichiro; Mori, Masaki; Nagano, Hiroaki.

In: International Journal of Cancer, Vol. 130, No. 2, 15.01.2012, p. 319-327.

Research output: Contribution to journalArticle

Tomimaru, Y, Eguchi, H, Wada, H, Kobayashi, S, Marubashi, S, Tanemura, M, Umeshita, K, Kim, T, Wakasa, K, Doki, Y, Mori, M & Nagano, H 2012, 'IGFBP7 downregulation is associated with tumor progression and clinical outcome in hepatocellular carcinoma', International Journal of Cancer, vol. 130, no. 2, pp. 319-327. https://doi.org/10.1002/ijc.25994
Tomimaru, Yoshito ; Eguchi, Hidetoshi ; Wada, Hiroshi ; Kobayashi, Shogo ; Marubashi, Shigeru ; Tanemura, Masahiro ; Umeshita, Koji ; Kim, Tonsok ; Wakasa, Kenichi ; Doki, Yuichiro ; Mori, Masaki ; Nagano, Hiroaki. / IGFBP7 downregulation is associated with tumor progression and clinical outcome in hepatocellular carcinoma. In: International Journal of Cancer. 2012 ; Vol. 130, No. 2. pp. 319-327.
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