Comprehensive analysis reveals a metabolic ten-gene signature in hepatocellular carcinoma
Background Due to the complicated molecular and cellular heterogeneity in hepatocellular carcinoma (HCC), the morbidity and mortality still remains high level in the world. However, the number of novel metabolic biomarkers and prognostic models could be applied to predict the survival of HCC patient...
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doaj-595530ebf9f3463384b8d4cf9c1d0fd92020-11-25T02:48:50ZengPeerJ Inc.PeerJ2167-83592020-05-018e920110.7717/peerj.9201Comprehensive analysis reveals a metabolic ten-gene signature in hepatocellular carcinomaZhipeng Zhu0Lulu Li1Jiuhua Xu2Weipeng Ye3Borong Chen4Junjie Zeng5Zhengjie Huang6Department of Gastrointestinal Surgery, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, ChinaDepartment of Gastrointestinal Surgery, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, ChinaDepartment of Clinical Medicine, Fujian Medical University, Xiamen, Fujian, ChinaDepartment of Clinical Medicine, Fujian Medical University, Xiamen, Fujian, ChinaDepartment of Gastrointestinal Surgery, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, ChinaDepartment of Gastrointestinal Surgery, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, ChinaDepartment of Gastrointestinal Surgery, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, ChinaBackground Due to the complicated molecular and cellular heterogeneity in hepatocellular carcinoma (HCC), the morbidity and mortality still remains high level in the world. However, the number of novel metabolic biomarkers and prognostic models could be applied to predict the survival of HCC patients is still small. In this study, we constructed a metabolic gene signature by systematically analyzing the data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and International Cancer Genome Consortium (ICGC). Methods Differentially expressed genes (DEGs) between tumors and paired non-tumor samples of 50 patients from TCGA dataset were calculated for subsequent analysis. Univariate cox proportional hazard regression and LASSO analysis were performed to construct a gene signature. The Kaplan–Meier analysis, time-dependent receiver operating characteristic (ROC), Univariate and Multivariate Cox regression analysis, stratification analysis were used to assess the prognostic value of the gene signature. Furthermore, the reliability and validity were validated in four types of testing cohorts. Moreover, the diagnostic capability of the gene signature was investigated to further explore the clinical significance. Finally, Go enrichment analysis and Gene Set Enrichment Analysis (GSEA) have been performed to reveal the different biological processes and signaling pathways which were active in high risk or low risk group. Results Ten prognostic genes were identified and a gene signature were constructed to predict overall survival (OS). The gene signature has demonstrated an excellent ability for predicting survival prognosis. Univariate and Multivariate analysis revealed the gene signature was an independent prognostic factor. Furthermore, stratification analysis indicated the model was a clinically and statistically significant for all subgroups. Moreover, the gene signature demonstrated a high diagnostic capability in differentiating normal tissue and HCC. Finally, several significant biological processes and pathways have been identified to provide new insights into the development of HCC. Conclusion The study have identified ten metabolic prognostic genes and developed a prognostic gene signature to provide more powerful prognostic information and improve the survival prediction for HCC.https://peerj.com/articles/9201.pdfHepatocellular carcinomaBioinformaticsGene signatureMetabolismSurvivalDiagnosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zhipeng Zhu Lulu Li Jiuhua Xu Weipeng Ye Borong Chen Junjie Zeng Zhengjie Huang |
spellingShingle |
Zhipeng Zhu Lulu Li Jiuhua Xu Weipeng Ye Borong Chen Junjie Zeng Zhengjie Huang Comprehensive analysis reveals a metabolic ten-gene signature in hepatocellular carcinoma PeerJ Hepatocellular carcinoma Bioinformatics Gene signature Metabolism Survival Diagnosis |
author_facet |
Zhipeng Zhu Lulu Li Jiuhua Xu Weipeng Ye Borong Chen Junjie Zeng Zhengjie Huang |
author_sort |
Zhipeng Zhu |
title |
Comprehensive analysis reveals a metabolic ten-gene signature in hepatocellular carcinoma |
title_short |
Comprehensive analysis reveals a metabolic ten-gene signature in hepatocellular carcinoma |
title_full |
Comprehensive analysis reveals a metabolic ten-gene signature in hepatocellular carcinoma |
title_fullStr |
Comprehensive analysis reveals a metabolic ten-gene signature in hepatocellular carcinoma |
title_full_unstemmed |
Comprehensive analysis reveals a metabolic ten-gene signature in hepatocellular carcinoma |
title_sort |
comprehensive analysis reveals a metabolic ten-gene signature in hepatocellular carcinoma |
publisher |
PeerJ Inc. |
series |
PeerJ |
issn |
2167-8359 |
publishDate |
2020-05-01 |
description |
Background Due to the complicated molecular and cellular heterogeneity in hepatocellular carcinoma (HCC), the morbidity and mortality still remains high level in the world. However, the number of novel metabolic biomarkers and prognostic models could be applied to predict the survival of HCC patients is still small. In this study, we constructed a metabolic gene signature by systematically analyzing the data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and International Cancer Genome Consortium (ICGC). Methods Differentially expressed genes (DEGs) between tumors and paired non-tumor samples of 50 patients from TCGA dataset were calculated for subsequent analysis. Univariate cox proportional hazard regression and LASSO analysis were performed to construct a gene signature. The Kaplan–Meier analysis, time-dependent receiver operating characteristic (ROC), Univariate and Multivariate Cox regression analysis, stratification analysis were used to assess the prognostic value of the gene signature. Furthermore, the reliability and validity were validated in four types of testing cohorts. Moreover, the diagnostic capability of the gene signature was investigated to further explore the clinical significance. Finally, Go enrichment analysis and Gene Set Enrichment Analysis (GSEA) have been performed to reveal the different biological processes and signaling pathways which were active in high risk or low risk group. Results Ten prognostic genes were identified and a gene signature were constructed to predict overall survival (OS). The gene signature has demonstrated an excellent ability for predicting survival prognosis. Univariate and Multivariate analysis revealed the gene signature was an independent prognostic factor. Furthermore, stratification analysis indicated the model was a clinically and statistically significant for all subgroups. Moreover, the gene signature demonstrated a high diagnostic capability in differentiating normal tissue and HCC. Finally, several significant biological processes and pathways have been identified to provide new insights into the development of HCC. Conclusion The study have identified ten metabolic prognostic genes and developed a prognostic gene signature to provide more powerful prognostic information and improve the survival prediction for HCC. |
topic |
Hepatocellular carcinoma Bioinformatics Gene signature Metabolism Survival Diagnosis |
url |
https://peerj.com/articles/9201.pdf |
work_keys_str_mv |
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