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启动子甲基化与肺腺癌患者预后不良相关。

Promoter Methylation is Associated with Poor Prognosis in Lung Adenocarcinoma Patients.

机构信息

Department of Thoracic Surgery, School of Medicine, Kyungpook National University, Daegu 702-422, Korea.

Department of Preventive Medicine, School of Medicine, Kyungpook National University, Daegu 702-422, Korea.

出版信息

Mol Cells. 2019 Feb 28;42(2):161-165. doi: 10.14348/molcells.2018.0322. Epub 2019 Jan 24.

DOI:10.14348/molcells.2018.0322
PMID:30726660
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6399005/
Abstract

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide and has high rates of metastasis. Transforming growth factor beta-inducible protein (TGFBI) is an extracellular matrix component involved in tumour growth and metastasis. However, the exact role of TGFBI in NSCLC remains controversial. Gene silencing via DNA methylation of the promoter region is common in lung tumorigenesis and could thus be used for the development of molecular biomarkers. We analysed the methylation status of the promoter in 138 NSCLC specimens via methylation-specific PCR and evaluated the correlation between methylation and patient survival. promoter methylation was detected in 25 (18.1%) of the tumours and was demonstrated to be associated with gene silencing. We observed no statistical correlation between methylation and clinicopathological characteristics. Univariate and multivariate analyses showed that methylation is significantly associated with poor survival outcomes in adenocarcinoma cases (adjusted hazard ratio = 2.88, 95% confidence interval = 1.19-6.99, = 0.019), but not in squamous cell cases. Our findings suggest that methylation in the promoter may be associated with pathogenesis of NSCLC and can be used as a predictive marker for lung adenocarcinoma prognosis. Further large-scale studies are needed to confirm these findings.

摘要

非小细胞肺癌(NSCLC)是全球癌症相关死亡的主要原因,且具有较高的转移率。转化生长因子β诱导蛋白(TGFBI)是一种细胞外基质成分,参与肿瘤生长和转移。然而,TGFBI 在 NSCLC 中的确切作用仍存在争议。通过启动子区域的 DNA 甲基化进行基因沉默在肺癌发生中很常见,因此可用于开发分子生物标志物。我们通过甲基化特异性 PCR 分析了 138 个 NSCLC 标本中的启动子甲基化状态,并评估了甲基化与患者生存之间的相关性。在 25 个(18.1%)肿瘤中检测到 启动子甲基化,且与基因沉默相关。我们观察到甲基化与临床病理特征之间无统计学相关性。单因素和多因素分析表明,在腺癌病例中, 甲基化与不良生存结果显著相关(调整后的危险比=2.88,95%置信区间=1.19-6.99,=0.019),但在鳞癌病例中无相关性。我们的研究结果表明, 启动子中的甲基化可能与 NSCLC 的发病机制有关,并可用作肺腺癌预后的预测标志物。需要进一步的大规模研究来证实这些发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc38/6399005/f148c00cde8a/molce-42-2-161f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc38/6399005/683ed4ee433d/molce-42-2-161f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc38/6399005/f148c00cde8a/molce-42-2-161f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc38/6399005/683ed4ee433d/molce-42-2-161f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc38/6399005/f148c00cde8a/molce-42-2-161f2.jpg

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