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pmid:33575212

Systematic Construction and Validation of an RNA-Binding Protein-Associated Model for Prognosis Prediction in Hepatocellular Carcinoma.

Siyuan Tian · Jingyi Liu · Keshuai Sun · Yansheng Liu · Jiahao Yu · Shuoyi Ma · Miao Zhang · Gui Jia · Xia Zhou · Yulong Shang · Ying Han

Frontiers in oncology · 2020 doi:10.3389/fonc.2020.597996

Paper

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Systematic Construction and Validation of an RNA-Binding Protein-Associated Model for Prognosis Prediction in Hepatocellular Carcinoma.
doi
10.3389/fonc.2020.597996
pmid
33575212
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[0]
Siyuan Tian
[1]
Jingyi Liu
[2]
Keshuai Sun
[3]
Yansheng Liu
[4]
Jiahao Yu
[5]
Shuoyi Ma
[6]
Miao Zhang
[7]
Gui Jia
[8]
Xia Zhou
[9]
Yulong Shang
[10]
Ying Han
journal
Frontiers in oncology
year
2020
abstract
BACKGROUND: Evidence from prevailing studies show that hepatocellular carcinoma (HCC) is among the top cancers with high mortality globally. Gene regulation at post-transcriptional level orchestrated by RNA-binding proteins (RBPs) is an important mechanism that modifies various biological behaviors of HCC. Currently, it is not fully understood how RBPs affects the prognosis of HCC. In this study, we aimed to construct and validate an RBP-related model to predict the prognosis of HCC patients. METHODS: Differently expressed RBPs were identified in HCC patients based on the GSE54236 dataset from the Gene Expression Omnibus (GEO) database. Integrative bioinformatics analyses were performed to select hub genes. Gene expression patterns were validated in The Cancer Genome Atlas (TCGA) database, after which univariate and multivariate Cox regression analyses, as well as Kaplan-Meier analysis were performed to develop a prognostic model. Then, the performance of the prognostic model was assessed using receiver operating characteristic (ROC) curves and clinicopathological correlation analysis. Moreover, data from the International Cancer Genome Consortium (ICGC) database were used for external validation. Finally, a nomogram combining clinicopathological parameters and prognostic model was established for the individual prediction of survival probability. RESULTS: The prognostic risk model was finally constructed based on two RBPs (BOP1 and EZH2), facilitating risk-stratification of HCC patients. Survival was markedly higher in the low-risk group relative to the high-risk group. Moreover, higher risk score was associated with advanced pathological grade and late clinical stage. Besides, the risk score was found to be an independent prognosis factor based on multivariate analysis. Nomogram including the risk score and clinical stage proved to perform better in predicting patient prognosis. CONCLUSIONS: The RBP-related prognostic model established in this study may function as a prognostic indicator for HCC, which could provide evidence for clinical decision making.
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Univariate Cox regression analysis was performed using the “survival” package in R software to identify prognostic factors from above prognosis-related RBPs. Variables with P < 0.05 in univariate analysis were further included in the stepwise multivariate analysis. A predictive model was then designed based on the independent prognostic factors.
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Univariate Cox regression analysis was performed using the “survival” package in R software to identify prognostic factors from above prognosis-related RBPs. Variables with P < 0.05 in univariate analysis were further included in the stepwise multivariate analysis. A predictive model was then designed based on the independent prognostic factors.
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The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/, GSE54236 https://cancergenome.nih.gov/, TCGA-LIHC https://dcc.icgc.org/, ICGC-JP.
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The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/, GSE54236 https://cancergenome.nih.gov/, TCGA-LIHC https://dcc.icgc.org/, ICGC-JP.
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Univariate Cox regression analysis was performed using the “survival” package in R software to identify prognostic factors from above prognosis-related RBPs. Variables with P < 0.05 in univariate analysis were further included in the stepwise multivariate analysis. A predictive model was then designed based on the independent prognostic factors.
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Gene regulation at post-transcriptional level orchestrated by RNA-binding proteins (RBPs) is an important mechanism that modifies various biological behaviors of HCC. Currently, it is not fully understood how RBPs affects the prognosis of HCC. In this study, we aimed to construct and validate an RBP-related model to predict the prognosis of HCC patients.\nMETHODS: Differently expressed RBPs were identified in HCC patients based on the GSE54236 dataset from the Gene Expression Omnibus (GEO) database. Integrative bioinformatics analyses were performed to select hub genes. Gene expression patterns were validated in The Cancer Genome Atlas (TCGA) database, after which univariate and multivariate Cox regression analyses, as well as Kaplan-Meier analysis were performed to develop a prognostic model. Then, the performance of the prognostic model was assessed using receiver operating characteristic (ROC) curves and clinicopathological correlation analysis. Moreover, data from the International Cancer Genome Consortium (ICGC) database were used for external validation. Finally, a nomogram combining clinicopathological parameters and prognostic model was established for the individual prediction of survival probability.\nRESULTS: The prognostic risk model was finally constructed based on two RBPs (BOP1 and EZH2), facilitating risk-stratification of HCC patients. Survival was markedly higher in the low-risk group relative to the high-risk group. Moreover, higher risk score was associated with advanced pathological grade and late clinical stage. Besides, the risk score was found to be an independent prognosis factor based on multivariate analysis. 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