title: Clinical Significance of IGFBP-3 Methylation in Patients with Early Stage Gastric Cancer.
abstract: 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.
authors: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Seung Tae
authors: ST
authors: Kim
authors: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; Samsung Biomedical Research Institute, Seoul, Korea.
authors: Hye-Lim
authors: HL
authors: Jang
authors: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Jeeyun
authors: J
authors: Lee
authors: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Se Hoon
authors: SH
authors: Park
authors: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Young Suk
authors: YS
authors: Park
authors: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Ho Yeong
authors: HY
authors: Lim
authors: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Min Gew
authors: MG
authors: Choi
authors: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Jae Moon
authors: JM
authors: Bae
authors: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Tae Sung
authors: TS
authors: Sohn
authors: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Jae Hyung
authors: JH
authors: Noh
authors: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Sung
authors: S
authors: Kim
authors: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Kyoung-Mee
authors: KM
authors: Kim
authors: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Won Ki
authors: WK
authors: Kang
authors: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. Electronic address: oncopark@skku.edu.
authors: Joon Oh
authors: JO
authors: Park