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前列腺癌诊断的表观遗传学前景。

The epigenetic promise for prostate cancer diagnosis.

机构信息

MDxHealth, Irvine, CA, USA.

出版信息

Prostate. 2012 Aug 1;72(11):1248-61. doi: 10.1002/pros.22459. Epub 2011 Dec 7.

Abstract

BACKGROUND

Prostate cancer is the most common cancer diagnosis in men and a leading cause of death. Improvements in disease management would have a significant impact and could be facilitated by the development of biomarkers, whether for diagnostic, prognostic, or predictive purposes. The blood-based prostate biomarker PSA has been part of clinical practice for over two decades, although it is surrounded by controversy. While debates of usefulness are ongoing, alternatives should be explored. Particularly with recent recommendations against routine PSA-testing, the time is ripe to explore promising biomarkers to yield a more efficient and accurate screening for detection and management of prostate cancer. Epigenetic changes, more specifically DNA methylation, are amongst the most common alterations in human cancer. These changes are associated with transcriptional silencing of genes, leading to an altered cellular biology.

METHODS

One gene in particular, GSTP1, has been widely studied in prostate cancer. Therefore a meta-analysis has been conducted to examine the role of this and other genes and the potential contribution to prostate cancer management and screening refinement.

RESULTS

More than 30 independent, peer reviewed studies have reported a consistently high sensitivity and specificity of GSTP1 hypermethylation in prostatectomy or biopsy tissue. The meta-analysis combined and compared these results.

CONCLUSIONS

GSTP1 methylation detection can serve an important role in prostate cancer managment. The meta-analysis clearly confirmed a link between tissue DNA hypermethylation of this and other genes and prostate cancer. Detection of DNA methylation in genes, including GSTP1, could serve an important role in clinical practice.

摘要

背景

前列腺癌是男性最常见的癌症诊断,也是主要死因之一。改善疾病管理将产生重大影响,而生物标志物的发展可能会为此提供便利,无论是用于诊断、预后还是预测目的。基于血液的前列腺生物标志物 PSA 已经在临床实践中应用了二十多年,尽管它存在争议。虽然关于其有效性的争论仍在继续,但应该探索替代方法。特别是鉴于最近建议反对常规 PSA 检测,现在正是探索有前途的生物标志物以提高前列腺癌检测和管理效率和准确性的好时机。表观遗传变化,特别是 DNA 甲基化,是人类癌症中最常见的变化之一。这些变化与基因转录沉默有关,导致细胞生物学发生改变。

方法

特别是 GSTP1 基因在前列腺癌中得到了广泛研究。因此,进行了荟萃分析来研究该基因和其他基因的作用及其对前列腺癌管理和筛查的潜在贡献。

结果

30 多项独立的同行评审研究报告称,GSTP1 过度甲基化在前列腺切除术或活检组织中具有高度的一致性和特异性。荟萃分析综合并比较了这些结果。

结论

GSTP1 甲基化检测可在前列腺癌管理中发挥重要作用。荟萃分析清楚地证实了组织 DNA 过度甲基化与前列腺癌之间的联系。包括 GSTP1 在内的基因的 DNA 甲基化检测可能在临床实践中发挥重要作用。

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