Translational Oncology (Aug 2015)

Clinical Significance of IGFBP-3 Methylation in Patients with Early Stage Gastric Cancer

  • Seung Tae Kim,
  • Hye-Lim Jang,
  • Jeeyun Lee,
  • Se Hoon Park,
  • Young Suk Park,
  • Ho Yeong Lim,
  • Min Gew Choi,
  • Jae Moon Bae,
  • Tae Sung Sohn,
  • Jae Hyung Noh,
  • Sung Kim,
  • Kyoung-Mee Kim,
  • Won Ki Kang,
  • Joon Oh Park

DOI
https://doi.org/10.1016/j.tranon.2015.06.001
Journal volume & issue
Vol. 8, no. 4
pp. 288 – 294

Abstract

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BACKGROUND: IGFBP-3 is a multifunctional protein that inhibits growth and induces apoptosis of cancer cells. Hypermethylation of the promoter represses expression of the IGFBP-3 gene. We undertook this study to assess the impact of IGFBP-3 methylation on survival of early stage gastric cancer patients. METHODS: Of the 482 tissue samples from gastric cancer patients who underwent curative surgery, IGFBP-3 methylation was tested in 138 patients with stage IB/II gastric cancer. We also analyzed IGFBP-3 methylation in 26 gastric cancer cell lines. IGFBP-3 methylation was evaluated by methylation-specific polymerase chain reaction (MethyLight). Statistical analyses, all two-sided, were performed to investigate the prognostic effects of methylation status of the IGFBP-3 promoter on various clinical parameters. RESULTS: Hypermethylation of IGFBP-3 was observed in 26 (19%) of the 138 stage IB/II gastric cancer patients. Clinicopathological factors such as age, Lauren classification, sex, tumor infiltration, lymph node metastasis, and histologic grade did not show a statistically significant association with the methylation status of the IGFBP-3 promoter. Patients with a hypermethylated IGFBP-3 promoter had similar 8-year disease-free survival compared with those without a hypermethylated IGFBP-3 promoter (73% vs 75%, P = .78). In subgroup analyses, females, but not males, seemed to have poorer prognosis for DFS and OS in the subset of patients with IGFBP-3 methylation as compared with those without IGFBP-3 methylation (8-year DFS: 55.6% vs 71.6%, P = .3694 and 8-year overall survival: 55.6% vs 68.4%, P = .491, respectively) even with no statistical significance. CONCLUSIONS: The status of IGFBP-3 methylation as measured by methylation-specific polymerase chain reaction proposed the modest role for predicting survival in specific subgroups of patients with early-stage gastric cancer who undergo curative surgery. However, this needs further investigation.