A Novel RNA Binding Protein-Related Prognostic Signature for Hepatocellular Carcinoma.

A Novel RNA Binding Protein-Related Prognostic Signature for Hepatocellular Carcinoma.
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一种新的 RNA 结合蛋白相关的肝细胞癌预后特征。

DOI:
10.3389/fonc.2020.580513
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发表时间:
2020
影响因子:
4.7
通讯作者:
Yuan X
Yuan X
中科院分区:
医学3区
文献类型:
--
作者:
Huang Y;Chen S;Qin W;Wang Y;Li L;Li Q;Yuan X

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肝细胞癌(HCC)是一种高度恶性和侵袭性的癌症,具有高复发率和死亡率。RNA结合蛋白(RNA binding proteins,RBP)参与多种肿瘤的发生发展,但在肝癌中的作用尚不清楚。我们从癌症基因组图谱(TCGA)数据库中下载了HCC的RNA-seq和相应的临床信息,并在正常和HCC组织之间鉴定了330个差异表达的RBP。通过一系列单变量、最小绝对收缩选择算子(LASSO)和逐步多变量考克斯回归分析,从DE RBP中筛选出6个与乳腺癌相关的关键RBP(hocT 6、UPF 3B、MRPL 54、ZC 3 H13、IFIT 5和PPARGC 1A),并在训练集中构建了6个RBP基因的风险评分特征。生存分析表明,高风险评分的HCC患者的总生存率明显低于低风险评分的HCC患者,并且该特征可作为独立的预后指标。ROC曲线分析证实了这种预后特征的良好准确性,并在国际癌症基因组联盟(ICGC)HCC队列中得到进一步验证。此外,建立了基于6个RBP基因的列线图,并在TCGA队列中进行了内部验证。基因集富集分析显示,一些与癌症相关的表型在高危人群中显著聚集。总体而言,我们的研究首次确定了RBP相关的六基因预后特征,这可能是一个有前途的预后生物标志物,并为HCC提供了一些潜在的治疗靶点。
Hepatocellular carcinoma (HCC) is a highly malignant and aggressive cancer with high recurrence rates and mortality. Some studies have illustrated that RNA binding proteins (RBPs) were involved in the carcinogenesis and development of multiple cancers, but the roles in HCC were still unclear. We downloaded the RNA-seq and corresponding clinical information of HCC from The Cancer Genome Atlas (TCGA) database, and 330 differentially expressed RBPs were identified between normal and HCC tissues. Through series of the univariate, the least absolute shrinkage selection operator (LASSO), and the stepwise multivariate Cox regression analyses, six prognosis-related key RBPs (CNOT6, UPF3B, MRPL54, ZC3H13, IFIT5, and PPARGC1A) were screened out from DE RBPs, and a six-RBP gene risk score signature was constructed in training set. Survival analysis indicated that HCC patients with high-risk scores had significantly worse overall survival than low-risk patients, and furthermore, the signature can be used as an independent prognostic indicator. The good accuracy of this prognostic signature was confirmed by the ROC curve analysis and was further validated in the International Cancer Genome Consortium (ICGC) HCC cohort. Besides, a nomogram based on six RBP genes was established and internally validated in the TCGA cohort. Gene set enrichment analysis demonstrated some cancer-related phenotypes were significantly gathered in the high-risk group. Overall, our study first identified an RBP-related six-gene prognostic signature, which could serve as a promising prognostic biomarker and provide some potential therapeutic targets for HCC.
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