甲基化印记:癌症诊疗、预后的重要指标

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甲基化印记:癌症诊疗、预后的重要指标 (原创文章www.777n.com)


(原文来自www.777n.com)

甲基化印记:癌症诊疗、预后的重要指标

(原创文章www.777n.com)


PNAS》期刊在线发表一篇题为“DNA methylation markers for diagnosis and prognosis of commoncancers”的文章,揭示DNA甲基化可以作为常见癌症的诊断和预后的重要标记物。

 

来自于加州大学圣地亚哥分校医学院、中山大学肿瘤防治中心、西京医院等研究机构的科研团队发现,DNA甲基化至少可以为4种常见癌症提供有效的分子标记,不仅仅可以准确诊断肿瘤组织,还可以作为预后的重要指标

 

DNA甲基化是指在DNA甲基化转移酶(Dnmt)的作用下将甲基(—CH3)选择性地添加至DNA上的过程,是一种基本的表观遗传学修饰。在不改变DNA序列的前提下控制基因的表达,在多个生物学过程中发挥重要作用,包括癌症的发生和发展。

 

“选择合适的治疗方案、争取最大的康复和生存几率,很大程度上依赖于精准确定癌症类型或亚型。”加州大学圣地亚哥分校基因组医学研究所创始主任Kang Zhang博士表示,“微创活检与DNA甲基化检测结合将会给癌症精准医学带来重要影响。以DNA甲基化为分子标签有望为癌症诊疗、预后提供更为精准的指标。”

 

研究团队在3种不同的数据库中分析4种常见癌症(肺癌、乳腺癌、结肠癌和肝癌)与正常人的DNA甲基化信息差异,并进行3组列队分析。他们发现,DNA甲基化检测能够检测癌症,且准确率达到95%。此外,甲基化检测还能够准确识别97%大肠癌肝转移和94%的大肠癌肺转移病例。

 

“由于10%的癌症属于转移性病变或者来源不明,所以癌组织的来源鉴定是选择有效治疗手段的关键。借助DNA甲基化检测,,有望解决10%的未知,确定肿瘤来源。”文章作者、加州大学圣地亚哥分校药理学教授Michael Karin解释。

 

研究人员认为,DNA甲基化可以通过更准确的诊断改善预后,特别是相对惰性或者侵袭性肿瘤。虽然这一研究只选取了4种常见癌症,但是他们认为,DNA甲基化检测可以应用于更多不同种类的癌症诊疗中。它的最大优势在于只需要少量的组织获得足够的DNA就可以完成检测。

 

参考文献:

DNA methylation markers for diagnosis andprognosis of common cancers

doi: 10.1073/pnas.1703577114

 

The ability to identify a specific cancerusing minimally invasive biopsy holds great promise for improving thediagnosis, treatment selection, and prediction of prognosis in cancer. Usingwhole-genome methylation data from The Cancer Genome Atlas (TCGA) and machinelearning methods, we evaluated the utility of DNA methylation fordifferentiating tumor tissue and normal tissue for four common cancers (breast,colon, liver, and lung). We identified cancer markers in a training cohort of1,619 tumor samples and 173 matched adjacent normal tissue samples. Wereplicated our findings in a separate TCGA cohort of 791 tumor samples and 93matched adjacent normal tissue samples, as well as an independent Chinesecohort of 394 tumor samples and 324 matched adjacent normal tissue samples. TheDNA methylation analysis could predict cancer versus normal tissue with morethan 95% accuracy in these three cohorts, demonstrating accuracy comparable totypical diagnostic methods. This analysis also correctly identified 29 of 30colorectal cancer metastases to the liver and 32 of 34 colorectal cancermetastases to the lung. We also found that methylation patterns can predictprognosis and survival. We correlated differential methylation of CpG sitespredictive of cancer with expression of associated genes known to be importantin cancer biology, showing decreased expression with increased methylation, asexpected. We verified gene expression profiles in a mouse model ofhepatocellular carcinoma. Taken together, these findings demonstrate theutility of methylation biomarkers for the molecular characterization of cancer,with implications for diagnosis and prognosis.

 

 

甲基化印记:癌症诊疗、预后的重要指标

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甲基化印记:癌症诊疗、预后的重要指标
甲基化印记:癌症诊疗、预后的重要指标



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