IGFBP - 3甲基化在早期胃癌患者中的临床意义
Clinical Significance of IGFBP-3 Methylation in Patients with Early Stage Gastric Cancer.
作者信息
Kim Seung Tae, Jang Hye-Lim, Lee Jeeyun, Park Se Hoon, Park Young Suk, Lim Ho Yeong, Choi Min Gew, Bae Jae Moon, Sohn Tae Sung, Noh Jae Hyung, Kim Sung, Kim Kyoung-Mee, Kang Won Ki, Park Joon Oh
机构信息
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; Samsung Biomedical Research Institute, Seoul, Korea.
出版信息
Transl Oncol. 2015 Aug;8(4):288-94. doi: 10.1016/j.tranon.2015.06.001.
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.
背景
胰岛素样生长因子结合蛋白3（IGFBP-3）是一种多功能蛋白，可抑制癌细胞生长并诱导其凋亡。启动子的高甲基化会抑制IGFBP-3基因的表达。我们开展本研究以评估IGFBP-3甲基化对早期胃癌患者生存的影响。
方法
在482例接受根治性手术的胃癌患者的组织样本中，对138例IB/II期胃癌患者检测了IGFBP-3甲基化情况。我们还分析了26种胃癌细胞系中的IGFBP-3甲基化情况。通过甲基化特异性聚合酶链反应（MethyLight）评估IGFBP-3甲基化。进行双侧统计分析以研究IGFBP-3启动子甲基化状态对各种临床参数的预后影响。
结果
138例IB/II期胃癌患者中，26例（19%）存在IGFBP-3高甲基化。年龄、劳伦分类、性别、肿瘤浸润、淋巴结转移和组织学分级等临床病理因素与IGFBP-3启动子甲基化状态无统计学显著关联。IGFBP-3启动子高甲基化的患者与未发生IGFBP-3启动子高甲基化的患者相比，8年无病生存率相似（73%对75%，P = 0.78）。在亚组分析中，与未发生IGFBP-3甲基化的患者相比，IGFBP-3甲基化患者亚组中的女性而非男性，无病生存和总生存预后似乎较差（8年无病生存率：55.6%对71.6%，P = 0.3694；8年总生存率：55.6%对68.4%，P = 0.491），即使无统计学意义。
结论
通过甲基化特异性聚合酶链反应检测的IGFBP-3甲基化状态提示，其在预测接受根治性手术的早期胃癌特定亚组患者生存方面作用不大。然而，这需要进一步研究。
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