Prognostic and predictive role of a metabolic rate-limiting enzyme signature in hepatocellular carcinoma.
Prognostic and predictive role of a metabolic rate-limiting enzyme signature in hepatocellular carcinoma.
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代谢限速酶特征在肝细胞癌中的预后和预测作用。
DOI：
10.1111/cpr.13117
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发表时间：
2021-10
影响因子：
8.5
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Wang Z;Fu Y;Xia A;Chen C;Qu J;Xu G;Zou X;Wang Q;Wang S
代谢速率限制酶的异常表达驱动肝细胞癌（HCC）的发生和进展。本研究旨在阐明代谢速率限制酶与HCC预后相关的综合模型。利用肝癌动物模型和TCGA项目筛选差异表达的代谢速率限制酶。进行了考克斯回归、最小绝对收缩和选择操作（LASSO）和实验验证，以确定代谢速率限制酶特征。使用受试者工作特征曲线下面积（AUC）和预后列线图评估三个HCC队列（TCGA训练队列、内部队列和独立验证队列）中签名的疗效。基于三种限速酶（RRM 1，UCK 2和G6 PD）进行分类，并作为独立的预后因素。在一个独立队列中进一步证实了该效应，表明临床风险评分在第5年的AUC为0.715（95% CI：0.653 - 0.777），而当结合临床和特征风险评分时，AUC显著增加至0.852（95% CI：0.798 - 0.906）。此外，包括签名和临床病理学方面的综合列线图导致显著预测个体结果。我们的研究结果强调了限速酶在HCC中的预后价值，这可能有助于指导临床管理和治疗决策的准确风险评估。第一步：基因本体论（GO）和京都基因和基因组百科全书（KEGG）对HCC动物差异表达基因的通路分析RNA测序数据将代谢通路中的大多数基因聚类。第二步：通过联合分析HCC动物模型的RNA-seq数据和TCGA数据中差异表达的代谢速率限制酶，有12个转录本重叠（RRM 1、SQLE、PCK 1、PYGB、G6 PD、PLAT、ACSL 1、RRM 2、UCK 2、ASS 1、FBP 1和IMPDH 1）。第三步：进行单变量和LASSO考克斯回归以筛选出具有显著总体预后的3种限速酶（i），使用三个HCC队列（TCGA训练队列、内部队列和独立验证队列）通过单变量/多变量考克斯回归、KM存活、ROC分析和列线图模型来验证代谢限速酶特征。
Abnormal expression of metabolic rate‐limiting enzymes drives the occurrence and progression of hepatocellular carcinoma (HCC). This study aimed to elucidate the comprehensive model of metabolic rate‐limiting enzymes associated with the prognosis of HCC. HCC animal model and TCGA project were used to screen out differentially expressed metabolic rate‐limiting enzyme. Cox regression, least absolute shrinkage and selection operation (LASSO) and experimentally verification were performed to identify metabolic rate‐limiting enzyme signature. The area under the receiver operating characteristic curve (AUC) and prognostic nomogram were used to assess the efficacy of the signature in the three HCC cohorts (TCGA training cohort, internal cohort and an independent validation cohort). A classifier based on three rate‐limiting enzymes (RRM1, UCK2 and G6PD) was conducted and serves as independent prognostic factor. This effect was further confirmed in an independent cohort, which indicated that the AUC at year 5 was 0.715 (95% CI: 0.653‐0.777) for clinical risk score, whereas it was significantly increased to 0.852 (95% CI: 0.798‐0.906) when combination of the clinical with signature risk score. Moreover, a comprehensive nomogram including the signature and clinicopathological aspects resulted in significantly predict the individual outcomes. Our results highlighted the prognostic value of rate‐limiting enzymes in HCC, which may be useful for accurate risk assessment in guiding clinical management and treatment decisions. Step1: Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of differentially expressed genes from HCC animals RNA‐seq data clustered the majority genes in metabolic pathways. Step2: By conjointly analyzing the differentially expressed metabolic rate‐limiting enzymes from RNA‐seq data of HCC animal model and TCGA data, 12 transcripts were overlapped (RRM1, SQLE, PCK1, PYGB, G6PD, PLAT, ACSL1, RRM2, UCK2, ASS1, FBP1 and IMPDH1). Step3: Univariate and LASSO Cox regression were performed to screen out 3 rate‐limiting enzymes with a significant overall prognosis(i), three HCC cohorts (TCGA training cohort, internal cohort and an independent validation cohort) were used to validate the metabolic rate‐limiting enzyme signature by Uni/Multivariate Cox regression, KM survival, ROC analysis and Nomogram model.
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影响因子：
9
作者：
Ma, Ling;Wang, Zhangding;Shu, Yongqian
通讯作者：
Shu, Yongqian
影响因子：
21.3
作者：
Boroughs LK;DeBerardinis RJ
通讯作者：
DeBerardinis RJ
DOI：
10.1186/s13046-019-1418-2
发表时间：
2019-10-26
影响因子：
11.3
作者：
Ou, Baochi;Sun, Hongze;Peng, Zhihai
通讯作者：
Peng, Zhihai
影响因子：
4.1
作者：
Germano, Antonina;Rapa, Ida;Terzolo, Massimo
通讯作者：
Terzolo, Massimo
影响因子：
4.1
作者：
Liu, Chien-Liang;Hsu, Yi-Chiung;Cheng, Shih-Ping
通讯作者：
Cheng, Shih-Ping