H-钙黏蛋白（CDH13）启动子的异常甲基化与原发性非小细胞肺癌的肿瘤进展相关。

Aberrant methylation of H-cadherin (CDH13) promoter is associated with tumor progression in primary nonsmall cell lung carcinoma.

作者信息

Kim Jin Seuk, Han Joungho, Shim Young Mog, Park Joobae, Kim Duk-Hwan

机构信息

Center for Genome Research, Samsung Biomedical Research Institute, 50 Ilwon-dong, Kangnam-Ku, Seoul, Korea.

出版信息

Cancer. 2005 Nov 1;104(9):1825-33. doi: 10.1002/cncr.21409.

DOI:10.1002/cncr.21409

PMID:16177988

Abstract

BACKGROUND

Abnormalities in the H-cadherin gene have been reported in several human malignancies, including nonsmall cell lung carcinoma (NSCLC). Aberrant methylation of the H-cadherin promoter also has been reported in NSCLC, but its clinical significance remains to be elucidated.

METHODS

The authors studied H-cadherin methylation in 305 patients with NSCLC to gain a further understanding of the clinicopathologic and prognostic significance of H-cadherin methylation in patients with NSCLC. The methylation status of the H-cadherin gene was investigated by using methylation-specific polymerase chain reaction analysis in paraffin blocks from 305 patients with NSCLC. Ki-67 expression was assessed by immunohistochemical staining. All statistical analyses were 2-sided with a 5% Type I error rate.

RESULTS

H-cadherin methylation was observed in 130 of 305 tumor samples (43%). The prevalence of H-cadherin methylation was associated significantly with pathologic stage and was observed in 44% of patients with Stage I disease, in 23% of patients with Stage II disease, in 59% of patients with Stage III, and in 88% of patients with Stage IV disease (P = 0.001). H-cadherin methylation occurred with a 2.71 times greater prevalence (95% confidence interval [95% CI], 1.21-6.09; P = 0.01) T2 tumors than in T1 tumors and with a 3.78-fold greater prevalence (95% CI, 1.05-13.59; P = 0.04) in T3 tumors than in T1 tumors. However, lymph node metastasis was related inversely with H-cadherin methylation (odds ratio = 0.51; 95% CI, 0.28-0.95; P = 0.03), and H-cadherin methylation was not associated with the Ki-67 labeling index (P = 0.53) or with tumor size (P = 0.89). No relation was found between H-cadherin methylation and survival in patients with Stage I NSCLC (P = 0.51) or in patients with Stage II NSCLC (P = 0.46).

CONCLUSIONS

The current findings suggested an association between H-cadherin methylation and tumor progression in NSCLC but had no prognostic significance in patients with early-stage NSCLC. In addition, H-cadherin methylation may be a valuable candidate molecular marker for the early detection of NSCLC.

摘要

背景

已有报道称，包括非小细胞肺癌（NSCLC）在内的多种人类恶性肿瘤中存在H-钙黏蛋白基因异常。NSCLC中也有H-钙黏蛋白启动子异常甲基化的报道，但其临床意义仍有待阐明。

方法

作者研究了305例NSCLC患者的H-钙黏蛋白甲基化情况，以进一步了解NSCLC患者中H-钙黏蛋白甲基化的临床病理及预后意义。采用甲基化特异性聚合酶链反应分析，对305例NSCLC患者石蜡块中的H-钙黏蛋白基因甲基化状态进行了研究。通过免疫组化染色评估Ki-67表达。所有统计分析均为双侧检验，I型错误率为5%。

结果

305个肿瘤样本中有130个（43%）检测到H-钙黏蛋白甲基化。H-钙黏蛋白甲基化的发生率与病理分期显著相关，I期疾病患者中为44%，II期疾病患者中为23%，III期患者中为59%，IV期患者中为88%（P = 0.001）。H-钙黏蛋白甲基化在T2肿瘤中的发生率比T1肿瘤高2.71倍（95%置信区间[95%CI]，1.21 - 6.09；P = 0.01），在T3肿瘤中的发生率比T1肿瘤高3.78倍（95%CI，1.05 - 13.59；P = 0.04）。然而，淋巴结转移与H-钙黏蛋白甲基化呈负相关（比值比 = 0.51；95%CI，0.28 - 0.95；P = 0.03），且H-钙黏蛋白甲基化与Ki-67标记指数（P = 0.53）或肿瘤大小（P = 0.89）无关。在I期NSCLC患者（P = 0.51）或II期NSCLC患者（P = 0.46）中，未发现H-钙黏蛋白甲基化与生存之间存在关联。