Contralateral upper tract urothelial carcinoma after nephroureterectomy: the predictive role of DNA methylation.
Contralateral upper tract urothelial carcinoma after nephroureterectomy: the predictive role of DNA methylation.
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肾输尿管切除术后对侧上尿路上皮癌：DNA 甲基化的预测作用
DOI：
10.1186/s13046-015-0120-2
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发表时间：
2015-01-22
期刊：
影响因子：
--
通讯作者：
Zhou L
中科院分区：
文献类型：
--
作者：
Zhang L;Xiong G;Fang D;Li X;Liu J;Ci W;Zhao W;Singla N;He Z;Zhou L
背景基因异常甲基化是尿路上皮癌发生发展中最常见的表观遗传修饰之一。然而，甲基化对根治性肾输尿管切除术（RNU）后对侧新发上尿路上皮癌（UTUC）的预测作用尚不清楚。我们回顾性研究的预测作用的DNA甲基化和其他临床病理因素在对侧上尿路上皮癌（UTUC）复发后，根治性肾输尿管切除术（RNU）在一个大的单中心cohort of patients.MethodsIn回顾性设计，10个基因的甲基化进行了分析，属于664个连续的原发性UTUC患者接受RNU治疗的肿瘤标本。中位随访时间为48个月（范围：3-144个月）。通过甲基化敏感的聚合酶链反应检测基因甲基化，并计算甲基化指数（MI），反映甲基化的程度。对数秩检验和考克斯回归被用来确定预测对侧UTUC recurrence.ResultsThirty（4.5%）患者开发了随后的对侧UTUC后，中位随访时间为27.5（范围：2-139）个月。88.9%的UTUC存在至少一个基因启动子位点的甲基化。对侧UTUC复发的肿瘤甲基化程度和MI均低于对侧无复发的肿瘤（P = 0.001）。高MI（P = 0.007）与癌症特异性生存率低显著相关。多因素分析表明，未甲基化的RASSF 1A（P = 0.039），对侧UTUC前无膀胱复发（P = 0.009），肾移植史（P < 0.001），术前肾功能不全（P = 0.002）是RNU后对侧UTUC复发的独立危险因素。结论我们的数据表明DNA甲基化在预测UTUC复发中的潜在作用。RNU后对侧UTUC复发。这些信息可以帮助识别RNU后新的对侧UTUC复发的高风险患者，这些患者在随访期间需要密切监测。
BackgroundAberrant methylation of genes is one of the most common epigenetic modifications involved in the development of urothelial carcinoma. However, it is unknown the predictive role of methylation to contralateral new upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). We retrospectively investigated the predictive role of DNA methylation and other clinicopathological factors in the contralateral upper tract urothelial carcinoma (UTUC) recurrence after radical nephroureterectomy (RNU) in a large single-center cohort of patients.MethodsIn a retrospective design, methylation of 10 genes was analyzed on tumor specimens belonging to 664 consecutive patients treated by RNU for primary UTUC. Median follow-up was 48 mo (range: 3–144 mo). Gene methylation was accessed by methylation-sensitive polymerase chain reaction, and we calculated the methylation index (MI), a reflection of the extent of methylation. The log-rank test and Cox regression were used to identify the predictor of contralateral UTUC recurrence.ResultsThirty (4.5%) patients developed a subsequent contralateral UTUC after a median follow-up time of 27.5 (range: 2–139) months. Promoter methylation for at least one gene promoter locus was present in 88.9% of UTUC. Fewer methylation and lower MI (P = 0.001) were seen in the tumors with contralateral UTUC recurrence than the tumors without contralateral recurrence. High MI (P = 0.007) was significantly correlated with poor cancer-specific survival. Multivariate analysis indicated that unmethylated RASSF1A (P = 0.039), lack of bladder recurrence prior to contralateral UTUC (P = 0.009), history of renal transplantation (P < 0.001), and preoperative renal insufficiency (P = 0.002) are independent risk factors for contralateral UTUC recurrence after RNU.ConclusionsOur data suggest a potential role of DNA methylation in predicting contralateral UTUC recurrence after RNU. Such information could help identify patients at high risk of new contralateral UTUC recurrence after RNU who need close surveillance during follow up.
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DOI：
10.1073/pnas.93.18.9821
发表时间：
1996-09-03
影响因子：
11.1
作者：
Herman, JG;Graff, JR;Baylin, SB
通讯作者：
Baylin, SB
影响因子：
6.6
作者：
Miyake, H;Hara, I;Eto, H
通讯作者：
Eto, H
影响因子：
23.4
作者：
Li, Ching-Chia;Chang, Tu-Hao;Huang, Chun-Hsiung
通讯作者：
Huang, Chun-Hsiung
影响因子：
6.2
作者：
Kang, CH;Yu, TJ;Shiue, YL
通讯作者：
Shiue, YL
影响因子：
11.5
作者：
Costa, Vera L.;Henrique, Rui;Lind, Guro E.
通讯作者：
Lind, Guro E.