Aberrant methylation of H-Cadherin (CDH13) promoter is associated with tumor progression in primary nonsmall cell lung carcinoma
Aberrant methylation of H-Cadherin (CDH13) promoter is associated with tumor progression in primary nonsmall cell lung carcinoma
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作者：
Kim, JS;Han, JH;Kim, DH
背景。h -钙粘蛋白基因的异常在包括非小细胞肺癌（NSCLC）在内的几种人类恶性肿瘤中都有报道。h -钙粘蛋白启动子的异常甲基化在非小细胞肺癌中也有报道，但其临床意义仍有待阐明。作者对305例NSCLC患者的H-cadherin甲基化进行了研究，以进一步了解H-cadherin甲基化在NSCLC患者中的临床病理和预后意义。采用甲基化特异性聚合酶链式反应分析305例NSCLC患者石蜡块中H-cadherin基因的甲基化状态。免疫组织化学染色检测Ki-67表达。所有统计分析均为双侧分析，I型错误率为5%。H-cadherin。305例肿瘤样本中有130例（43%）出现甲基化。h -钙粘蛋白甲基化的患病率与病理分期显著相关，在44%的I期患者、23%的11期患者、59%的111期患者和88%的IV期患者中均存在h -钙粘蛋白甲基化（P = 0.001）。H-cadherin甲基化在T2肿瘤中的发生率是T1肿瘤的2.71倍（95%可信区间[95% CI]， 1.21-6.09; P = 0.01），在T3肿瘤中的发生率是T1肿瘤的3.78倍（95% Cl, 1.05-13.59; P = 0.04）。然而，淋巴结转移与H-cadherin甲基化呈负相关（优势比= 0.51;95% Cl, 0.28-0.95; P = 0.03）， H-cadherin甲基化与Ki-67标记指数（P = 0.53）和肿瘤大小（P = 0.89）无关。在I期NSCLC患者（P = 0.51）和11期NSCLC患者（P = 0.46）中，H-cadherin甲基化与生存率无相关性。目前的研究结果表明，H-cadherin甲基化与非小细胞肺癌的肿瘤进展有关，但对早期非小细胞肺癌患者没有预后意义。此外，h -钙粘蛋白甲基化可能是早期检测非小细胞肺癌的一个有价值的候选分子标志物。
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 11 disease, in 59% of patients with Stage 111, 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% Cl, 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% Cl, 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 11 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.