Methylation pattern analysis in prostate cancer tissue: identification of biomarkers using an MS-MLPA approach.

Methylation pattern analysis in prostate cancer tissue: identification of biomarkers using an MS-MLPA approach.
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前列腺癌组织中的甲基化模式分析:使用 MS-MLPA 方法鉴定生物标志物。

DOI:
10.1186/s12967-016-1014-6
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发表时间:
2016-08-30
影响因子:
7.4
通讯作者:
Casadio V
Casadio V
中科院分区:
医学2区
文献类型:
--
作者:
Gurioli G;Salvi S;Martignano F;Foca F;Gunelli R;Costantini M;Cicchetti G;De Giorgi U;Sbarba PD;Calistri D;Casadio V

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由CpG岛甲基化介导的表观遗传沉默是许多癌症的共同特征。表征与前列腺癌发生相关的异常DNA甲基化变化可能会识别肿瘤特异性甲基化模式,从而促进前列腺癌的早期诊断。该研究的目的是评估前列腺癌和健康前列腺组织中40个肿瘤抑制基因的甲基化状态。我们在两个独立的病例系列(训练集和验证集)中使用甲基化特异性多重连接探针扩增(MS-MLPA)测定。训练集包括前列腺癌组织(n = 40)、邻近肿瘤的健康前列腺组织(n = 26)和健康非前列腺组织(n = 23)的样品,总共89个DNA样品;验证集由40个前列腺癌组织样品及其邻近的健康前列腺组织组成,总共80个DNA样品。甲基化特异性聚合酶链反应(MSP)用于确认验证集中获得的结果。我们在前列腺癌中鉴定了5个高度甲基化的基因:GSTP 1、RARB、RASSF 1、SCGB 3A 1、CCND 2(P < 0.0001),ROC曲线下面积在0.89(95%CI 0.82-0.97)和0.95(95%CI 0.90-1.00)之间变化。诊断准确性范围为80%(95%CI 70-88)至90%(95%CI 81-96)。此外,观察到MS-MLPA和MSP之间的一致率范围为83%(95% CI 72-90)至89%(95% CI 80-95)。我们的初步研究结果表明,GSTP 1,RARB,RASSF 1,SCGB 3A 1和CCND 2的高甲基化在前列腺癌组织中具有高度的肿瘤特异性。本文的在线版本(doi:10.1186/s12967-016-1014-6)包含补充材料,可供授权用户使用。
Epigenetic silencing mediated by CpG island methylation is a common feature of many cancers. Characterizing aberrant DNA methylation changes associated with prostate carcinogenesis could potentially identify a tumour-specific methylation pattern, facilitating the early diagnosis of prostate cancer. The objective of the study was to assess the methylation status of 40 tumour suppressor genes in prostate cancer and healthy prostatic tissues. We used methylation specific-multiplex ligation probe amplification (MS-MLPA) assay in two independent case series (training and validation set). The training set comprised samples of prostate cancer tissue (n = 40), healthy prostatic tissue adjacent to the tumor (n = 26), and healthy non prostatic tissue (n = 23), for a total of 89 DNA samples; the validation set was composed of 40 prostate cancer tissue samples and their adjacent healthy prostatic tissue, for a total of 80 DNA samples. Methylation specific-polymerase chain reaction (MSP) was used to confirm the results obtained in the validation set. We identified five highly methylated genes in prostate cancer: GSTP1, RARB, RASSF1, SCGB3A1, CCND2 (P < 0.0001), with an area under the ROC curve varying between 0.89 (95 % CI 0.82–0.97) and 0.95 (95 % CI 0.90–1.00). Diagnostic accuracy ranged from 80 % (95 % CI 70–88) to 90 % (95 % CI 81–96). Moreover, a concordance rate ranging from 83 % (95 % CI 72–90) to 89 % (95 % CI 80–95) was observed between MS-MLPA and MSP. Our preliminary results highlighted that hypermethylation of GSTP1, RARB, RASSF1, SCGB3A1 and CCND2 was highly tumour-specific in prostate cancer tissue. The online version of this article (doi:10.1186/s12967-016-1014-6) contains supplementary material, which is available to authorized users.
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