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Construction and Validation of an Autophagy-Related Prognostic Signature and a Nomogram for Bladder Cancer

机译:与膀胱癌的自噬相关预后签名的构建与验证和膀胱癌的载体

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摘要

ObjectiveBladder cancer (BC) is one of the top ten cancers endangering human health but we still lack accurate tools for BC patients’ risk stratification. This study aimed to develop an autophagy-related signature that could predict the prognosis of BC. In order to provide clinical doctors with a visual tool that could precisely predict the survival probability of BC patients, we also attempted to establish a nomogram based on the risk signature.MethodsWe screened out autophagy-related genes (ARGs) combining weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) in BC. Based on the screened ARGs, we performed survival analysis and Cox regression analysis to identify potential prognostic biomarkers. A risk signature based on the prognostic ARGs by multivariate Cox regression analysis was established, which was validated by using seven datasets. To provide clinical doctors with a useful tool for survival possibility prediction, a nomogram assessed by the ARG-based signature and clinicopathological features was constructed, verified using four independent datasets.ResultsThree prognostic biomarkers including BOC (P = 0.008, HR = 1.104), FGF7(P = 0.030, HR = 1.066), and MAP1A (P = 0.001, HR = 1.173) were identified and validated. An autophagy-related risk signature was established and validated. This signature could act as an independent prognostic feature in patients with BC (P = 0.047, HR = 1.419). We then constructed two nomograms with and without ARG-based signature and subsequent analysis indicated that the nomogram with ARG signature showed high accuracy for overall survival probability prediction of patients with BC (C-index = 0.732, AUC = 0.816). These results proved that the ARG signature improved the clinical net benefit of the standard model based on clinicopathological features (age, pathologic stage).ConclusionsThree ARGs were identified as prognosis biomarkers in BC. An ARG-based signature was established for the first time, showing strong potential for prognosis prediction in BC. This signature was proven to improve the clinical net benefit of the standard model. A nomogram was established using this signature, which could lead to more effective prognosis prediction for BC patients.
机译:目的是癌症(BC)是危及人类健康的十大癌症之一,但我们仍然缺乏对BC患者风险分层的准确工具。本研究旨在开发有关的自噬相关签名,可以预测BC的预后。为了提供可以精确预测BC患者的存活概率的视觉工具,我们还试图根据风险签名建立一个铭文。筛选筛选的自噬相关基因(Args)组合加权基因共表达BC中的网络分析(WGCNA)和差异表达基因(DEG)。基于筛选的args,我们进行了生存分析和Cox回归分析以识别潜在的预后生物标志物。建立了基于多元硬盘回归分析的基于预后args的风险特征,通过使用七个数据集来验证。为了提供具有用于生存可能预测的有用工具的临床医生,构建了基于ARG的签名和临床病理学特征评估的ROM图,使用四个独立的数据集进行了验证,包括BOC(P = 0.008,HR = 1.104),FGF7 (P = 0.030,HR = 1.066)和MAP1A(P = 0.001,HR = 1.173)被验证并验证。建立和验证了与自动侵害相关的风险签名。这种签名可以作为BC患者的独立预后特征(P = 0.047,HR = 1.419)。然后,我们构建了两个具有基于arg的签名和随后分析的载体图表,表明具有arg签名的NOM图对BC患者的整体存活概率预测显示出高精度(C-INDEX = 0.732,AUC = 0.816)。这些结果证明,Arg签名基于临床病理特征(年龄,病理阶段)改善了标准模型的临床净利益。结论抗原args被鉴定为BC的预后生物标志物。第一次建立了基于arg的签名,显示了BC预后预测的强大潜力。该签名被证明是为了改善标准模型的临床净利润。使用该签名建立了一个载体,这可能导致BC患者的更有效预后预测。

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