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建立并验证一个与 MTORC1 信号相关的基因特征,以预测肝细胞癌患者的总生存期。

Establishment and Validation of an MTORC1 Signaling-Related Gene Signature to Predict Overall Survival in Patients with Hepatocellular Carcinoma.

机构信息

Department of Radiology Intervention, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, 310000 Zhejiang, China.

出版信息

Biomed Res Int. 2021 Nov 22;2021:6299472. doi: 10.1155/2021/6299472. eCollection 2021.

Abstract

BACKGROUND

Accurate and effective biomarkers for the prognosis of patients with hepatocellular carcinoma (HCC) are poorly identified. A network-based gene signature may serve as a valuable biomarker to improve the accuracy of risk discrimination in patients.

METHODS

The expression levels of cancer hallmarks were determined by Cox regression analysis. Various bioinformatic methods, such as GSEA, WGCNA, and LASSO, and statistical approaches were applied to generate an MTORC1 signaling-related gene signature (MSRS). Moreover, a decision tree and nomogram were constructed to aid in the quantification of risk levels for each HCC patient.

RESULTS

Active MTORC1 signaling was found to be the most vital predictor of overall survival in HCC patients in the training cohort. MSRS was established and proved to hold the capacity to stratify HCC patients with poor outcomes in two validated datasets. Analysis of the patient MSRS levels and patient survival data suggested that the MSRS can be a valuable risk factor in two validated datasets and the integrated cohort. Finally, we constructed a decision tree which allowed to distinguish subclasses of patients at high risk and a nomogram which could accurately predict the survival of individuals.

CONCLUSIONS

The present study may contribute to the improvement of current prognostic systems for patients with HCC.

摘要

背景

目前,对于肝细胞癌(HCC)患者预后的准确有效的生物标志物尚未明确。基于网络的基因特征可作为有价值的生物标志物,以提高对患者风险区分的准确性。

方法

采用 Cox 回归分析确定癌症特征的表达水平。应用各种生物信息学方法(如 GSEA、WGCNA 和 LASSO)和统计方法生成 MTORC1 信号相关基因特征(MSRS)。此外,构建决策树和列线图以帮助量化每位 HCC 患者的风险水平。

结果

在训练队列中,活跃的 MTORC1 信号被发现是 HCC 患者总生存期的最重要预测因素。建立了 MSRS 并证明其能够在两个验证数据集中对预后不良的 HCC 患者进行分层。对患者 MSRS 水平和患者生存数据的分析表明,MSRS 可以作为两个验证数据集和整合队列中的一个有价值的风险因素。最后,我们构建了一个决策树,可以区分高危患者的亚类,以及一个列线图,可以准确预测个体的生存情况。

结论

本研究可能有助于改善目前 HCC 患者的预后系统。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bd7/8629633/5b1fadeb892a/BMRI2021-6299472.001.jpg

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