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首页> 外文期刊>Lung cancer: Journal of the International Association for the Study of Lung Cancer >Promoter hypermethylation of RASSF1A and RUNX3 genes as an independent prognostic prediction marker in surgically resected non-small cell lung cancers.
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Promoter hypermethylation of RASSF1A and RUNX3 genes as an independent prognostic prediction marker in surgically resected non-small cell lung cancers.

机译:RASSF1A基因启动子甲基化和RUNX3作为一个独立的预后预测的基因标记在手术切除非小细胞肺癌症。

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摘要

Aberrant methylation of promoter CpG islands is known to be a major inactivation mechanism of the tumor suppressor and tumor-related genes. Some published studies suggest a relationship to exist between the methylation status of several genes and the prognosis in non-small cell lung cancer (NSCLC); hypermethylation of the specific genes may be expected to serve as a biomarker for the prognosis, after a curative resection of NSCLC. To determine the relationship between the methylation status of the tumor suppressor and the tumor-related genes, and the clinicopathologic characteristics, including the survival rate, in patients with NSCLC after a surgical resection, we studied methylation in 10 genes (DAPK, FHIT, H-cadherin, MGMT, p14, p16, RAR-beta, RASSF1A, RUNX3, and TIMP-3) in 101 NSCLC cases by methylation-specific PCR (MSP). The methylation frequencies of the 10 genes examined in NSCLC were 26% for DAPK, 34% for FHIT, 26% for H-cadherin, 14% for MGMT, 8% for p14, 27% for p16, 38% for RAR-beta, 42% for RASSF1A, 25% for RUNX3, and 12% for TIMP-3. Clinicopathologically, the patients with all stages of disease who had positive RASSF1A, RUNX3, or H-cadherin methylation status were found to have a significantly shorter duration of survival, as compared with the patients with a negative methylation status for those genes (RASSF1A:P=0.023, RUNX3:P=0.035, H-cadherin:P=0.039) in univariate analysis. Thereafter, while limiting our examination to patients with stage I disease, the patients who had a positive RASSF1A or RUNX3 methylation status were found to have a significantly shorter duration of survival, in comparison to the patients with negative methyaltion status for each of those genes (RASSF1A:P=0.022, RUNX3:P<0.01) in univariate analysis. Next, the histological differences were recognized that the patients with RUNX3 methylation had a shorter duration of survival in adenocarcinomas (ACs) (P=0.045), in contrast to those with RASSF1A methylation who had a shorter duration of survival in squamous cell carcinomas (SCCs) (P=0.021). In multivariate analysis, both positive RASSF1A methylation status, and positive RUNX3 methylation status were found to be independent prognostic factors (RASSF1A:P=0.031, RUNX3:P=0.028), as was TNM stage (P=0.004) and pleural involvement (P=0.037). In conclusion, the hypermethylation of RASSF1A or RUNX3 gene is therefore a useful biomarker to predict the prognosis in NSCLC, particularly RASSF1A due to SCCs and RUNX3 due to ACs.
机译:异常的启动子的甲基化CpG岛已知的主要失活机制肿瘤抑制基因和肿瘤。发表的研究显示存在的关系几个基因的甲基化状态之间和非小细胞肺癌的预后(NSCLC);可能将作为生物标志物吗治疗后预后,切除的非小细胞肺癌。确定之间的关系肿瘤抑制基因的甲基化状态肿瘤基因,临床病理的特点,包括与非小细胞肺癌患者的生存率,之后手术切除,我们研究了甲基化在10FHIT基因,基因(DAPK H-cadherin、管理好,p16,RAR-beta RASSF1A基因,RUNX3和TIMP-3)在101年非小细胞肺癌病例由methylation-specific聚合酶链反应(MSP)。10基因的甲基化频率检测在非小细胞肺癌是DAPK为26%,34%管理H-cadherin FHIT基因,26%,14%,8%RAR-beta p16好,27%,38%,42%TIMP-3 RUNX3 RASSF1A基因,25%,12%。临床病理的,所有患者阶段的疾病积极RASSF1A基因,RUNX3或H-cadherin甲基化状态发现有明显更短的时间生存,与患者相比-这些基因甲基化状态在单变量分析H-cadherin: P = 0.039)。此后,同时限制我们的考试I期疾病患者,患者有一个积极的RASSF1A基因甲基化或RUNX3吗地位有明显缩短的生存时间,相比患者负methyaltion状态每一个基因(RASSF1A基因:P = 0.022,在单变量分析RUNX3: P < 0.01)。组织学差异被认识到RUNX3患者甲基化有一个短在腺癌生存时间(ACs)(P = 0.045),而那些RASSF1A基因甲基化的持续时间较短生存在鳞状细胞癌(癌)(P = 0.021)。积极RASSF1A基因甲基化状态和积极的RUNX3甲基化状态被发现独立的预后因素(RASSF1A基因:P = 0.031,RUNX3: P = 0.028), TNM阶段(P = 0.004)胸膜受累(P = 0.037)。RASSF1A基因的甲基化或RUNX3基因因此一个有用的生物标志物来预测的在非小细胞肺癌预后,特别是RASSF1A基因由于癌和RUNX3 ACs。

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