A Novel DNA Methylation Signature as an Independent Prognostic Factor in Muscle-Invasive Bladder Cancer.
A Novel DNA Methylation Signature as an Independent Prognostic Factor in Muscle-Invasive Bladder Cancer.
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DOI：
10.3389/fonc.2021.614927
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发表时间：
2021
影响因子：
4.7
通讯作者：
Liang G
中科院分区：
文献类型：
--
作者：
Xu Z;Gujar H;Fu G;Ahmadi H;Bhanvadia S;Weisenberger DJ;Jin B;Gill PS;Gill I;Daneshmand S;Siegmund KD;Liang G
肌肉浸润性膀胱癌（MIBC）在诊断时约占所有尿路上皮膀胱癌（UBC）的20%，并且随着时间的推移，高达30%的非肌肉浸润性UBC患者将进展为MIBC。越来越多的证据表明，DNA甲基化异常与MIBC的肿瘤发生之间存在很强的相关性。使用413例患者的癌症基因组图谱（TCGA）分子数据，我们描述了一种基于DNA甲基化的标记作为MIBC患者总生存期（OS）的预后因素。通过使用最小绝对收缩和选择算子（LASSO）模型，首先使用多个标准鉴定差异甲基化区域，然后通过生存和LASSO分析鉴定与OS相关的DNA甲基化探针，并建立分类器对MIBC患者进行分层。分类器的预后价值（称为风险评分（RS））在TCGA MIBC队列的保留测试集中进行了验证。最后，使用受试者工作特征（ROC）分析比较RS单独、RS加临床病理特征和临床病理特征单独建立的模型的预后准确性。我们发现，我们基于七探针分类器的RS在测试集中将患者分为总生存期（OS）的高风险组和低风险组（n = 137）（3年时的AUC，0.65; 5年时的AUC，0.65）。此外，当RS与包括年龄、吸烟状况、肿瘤（T）分期和淋巴结转移（N）分期的临床信息相结合时，RS显著改善了预后模型。基于DNA甲基化的RS可以作为预测MIBC患者术前和/或术后OS模型准确性的有用工具。
Muscle-invasive bladder cancer (MIBC) accounts for approximately 20% of all urothelial bladder carcinomas (UBC) at time of diagnosis, and up to 30% of patients with non-muscle invasive UBC will progress to MIBC over time. An increasing body of evidence has revealed a strong correlation between aberrant DNA methylation and tumorigenesis in MIBC. Using The Cancer Genome Atlas (TCGA) molecular data for 413 patients, we described a DNA methylation-based signature as a prognostic factor for overall survival (OS) in MIBC patients. By using a least absolute shrinkage and selection operator (LASSO) model, differentially methylated regions were first identified using multiple criteria followed by survival and LASSO analyses to identify DNA methylation probes related to OS and build a classifier to stratify patients with MIBC. The prognostic value of the classifier, referred to as risk score (RS), was validated in a held-out testing set from the TCGA MIBC cohort. Finally, receiver operating characteristic (ROC) analysis was used to compare the prognostic accuracy of the models built with RS alone, RS plus clinicopathologic features, and clinicopathologic features alone. We found that our seven-probe classifier-based RS stratifies patients into high- and low-risk groups for overall survival (OS) in the testing set (n = 137) (AUC at 3 years, 0.65; AUC at 5 years, 0.65). In addition, RS significantly improved the prognostic model when it was combined with clinical information including age, smoking status, Tumor (T) stage, and Lymph node metastasis (N) stage. The DNA methylation-based RS can be a useful tool to predict the accuracy of preoperative and/or post-cystectomy models of OS in MIBC patients.
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循环肿瘤 DNA 甲基化谱可实现结直肠癌的早期诊断、预后预测和筛查
影响因子：
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作者：
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