Adenomatous polyposis coli gene promoter hypermethylation in non-small cell lung cancer is associated with survival
Adenomatous polyposis coli gene promoter hypermethylation in non-small cell lung cancer is associated with survival
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DOI：
10.1038/sj.onc.1204455
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发表时间：
2001-06-14
期刊：
影响因子：
8
通讯作者：
Danenberg, PV
中科院分区：
文献类型：
--
作者：
Brabender, J;Usadel, H;Danenberg, PV
启动子和上游编码区的5 ' CpG岛甲基化已被确定为肿瘤抑制基因转录失活的机制。本研究的目的是确定原发性非小细胞肺癌（NSCLC）中是否存在结肠腺瘤性息肉病（APC）基因启动子的高甲基化，以及APC高甲基化是否与生存率有关。使用定量荧光实时PCR（Taqman（（R）系统，在91名NSCLC患者的正常和相应肿瘤组织中以及10名非癌症患者的对照组中测定APC启动子1A甲基化。APC启动子甲基化在91个肿瘤样本中的86个（95%）中可检测到，但在91个NSCLC患者的正常样本中的80个（88%）中也可检测到，并且在对照组的10个正常肺组织中仅2个（20%）中可检测到。APC基因启动子甲基化的中位数在肿瘤组织中为4.75，而在正常肺组织中为1.57（P < 0.001），低甲基化状态患者的生存期明显长于高甲基化状态患者多因素分析显示，APC基因甲基化是影响预后的独立因素（P = 0.041）pT（P = 0.050）和pN（P < 0.001）分级也是如此。本研究表明APC基因启动子甲基化发生在大多数原发性NSCLC中，APC启动子高甲基化与低生存率显著相关，显示出作为NSCLC生物学侵袭性疾病的生物标志物的前景。
Methylation of 5 ' CpG islands in promoter and upstream coding regions has been identified as a mechanism for transcriptional inactivation of tumor suppressor genes. The purpose of this study was to determine whether hypermethylation of the adenomatous polyposis coli (APC) gene promoter occurs in primary non-small cell lung cancer (NSCLC), and whether hypermethylated APC has any relationship with survival. APC promoter 1A methylation was determined in normal and corresponding tumor tissue from 91 NSCLC patients and in a control group of 10 patients without cancer, using a quantitative fluorogenic real-time PCR (Taqman((R))) system. APC promoter methylation was detectable in 86 (95%) of 91 tumor samples, but also in 80 (88%) of 91 normal samples of NSCLC patients, and in only two (20%) of 10 normal lung tissues of the control group. The median level of APC promoter methylation was 4.75 in tumor compared to 1.57 in normal lung tissue (P < 0.001), Patients with low methylation status showed significantly longer survival than did patients with high methylation status (P = 0.041), In a multivariate analysis of prognostic factors, APC methylation was a significant independent prognostic factor (P = 0.044), as were pT (P = 0.050) and pN (P < 0.001) classifications. This investigation shows that APC gene promoter methylation occurs in the majority of primary NSCLCs, High APC promoter methylation is significantly associated with inferior survival, showing promise as a biomarker of biologically aggressive disease in NSCLC.