Gurioli Giorgia, Salvi Samanta, Martignano Filippo, Foca Flavia, Gunelli Roberta, Costantini Matteo, Cicchetti Giacomo, De Giorgi Ugo, Sbarba Persio Dello, Calistri Daniele, Casadio Valentina
Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via P. Maroncelli 40, 47014, Meldola, Italy.
Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via P. Maroncelli 40, 47014, Meldola, Italy.
J Transl Med. 2016 Aug 30;14(1):249. doi: 10.1186/s12967-016-1014-6.
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.
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出肿瘤特异性甲基化模式，有助于前列腺癌的早期诊断。本研究的目的是评估40个肿瘤抑制基因在前列腺癌组织和健康前列腺组织中的甲基化状态。
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）检测。训练集包括前列腺癌组织样本（n = 40）、肿瘤旁健康前列腺组织样本（n = 26）和健康非前列腺组织样本（n = 23），共89个DNA样本；验证集由40个前列腺癌组织样本及其相邻的健康前列腺组织组成，共80个DNA样本。甲基化特异性聚合酶链反应（MSP）用于确认在验证集中获得的结果。
我们在前列腺癌中鉴定出5个高度甲基化的基因：GSTP1、RARB、RASSF1、SCGB3A1、CCND2（P < 0.0001），ROC曲线下面积在0.89（95%CI 0.82 - 0.97）至0.95（95%CI 0.90 - 1.00）之间。诊断准确率在80%（95%CI 70 - 88）至90%（95%CI 81 - 96）之间。此外，MS-MLPA和MSP之间的一致性率在83%（95%CI 72 - 90）至89%（95%CI 80 - 95）之间。
我们的初步结果表明，GSTP1、RARB、RASSF1、SCGB3A1和CCND2的高甲基化在前列腺癌组织中具有高度肿瘤特异性。
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