A Novel Ten-Gene Signature Predicting Prognosis in Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) has a dismal long-term outcome. We aimed to construct a multi-gene model for prognosis prediction to inform HCC management. The cancer-specific differentially expressed genes (DEGs) were identified using RNA-seq data of paired tumor and normal tissue. A prognostic sign...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-07-01
|
| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2020.00629/full |
| _version_ | 1818248358501810176 |
|---|---|
| author | Taicheng Zhou Zhihua Cai Ning Ma Wenzhuan Xie Chan Gao Mengli Huang Yuezong Bai Yangpeng Ni Yunqiang Tang |
| author_facet | Taicheng Zhou Zhihua Cai Ning Ma Wenzhuan Xie Chan Gao Mengli Huang Yuezong Bai Yangpeng Ni Yunqiang Tang |
| author_sort | Taicheng Zhou |
| collection | DOAJ |
| description | Hepatocellular carcinoma (HCC) has a dismal long-term outcome. We aimed to construct a multi-gene model for prognosis prediction to inform HCC management. The cancer-specific differentially expressed genes (DEGs) were identified using RNA-seq data of paired tumor and normal tissue. A prognostic signature was built by LASSO regression analysis. Gene set enrichment analysis (GSEA) was performed to further understand the underlying molecular mechanisms. A 10-gene signature was constructed to stratify the TCGA and ICGC cohorts into high- and low-risk groups where prognosis was significantly worse in the high-risk group across cohorts (P < 0.001 for all). The 10-gene signature outperformed all previously reported models for both C-index and the AUCs for 1-, 3-, 5-year survival prediction (C-index, 0.84 vs 0.67 to 0.73; AUCs for 1-, 3- and 5-year OS, 0.84 vs 0.68 to 0.79, 0.81 to 0.68 to 0.80, and 0.85 vs 0.67 to 0.78, respectively). Multivariate Cox regression analysis revealed risk group and tumor stage to be independent predictors of survival in HCC. A nomogram incorporating tumor stage and signature-based risk group showed better performance for 1- and 3-year survival than for 5-year survival. GSEA revealed enrichment of pathways related to cell cycle regulation among high-risk samples and metabolic processes in the low-risk group. Our 10-gene model is robust for prognosis prediction and may help inform clinical management of HCC. |
| first_indexed | 2024-12-12T15:19:20Z |
| format | Article |
| id | doaj.art-b0a57a51a3034d6bbea35fd021acd425 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-12T15:19:20Z |
| publishDate | 2020-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-b0a57a51a3034d6bbea35fd021acd4252022-12-22T00:20:25ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-07-01810.3389/fcell.2020.00629540526A Novel Ten-Gene Signature Predicting Prognosis in Hepatocellular CarcinomaTaicheng Zhou0Zhihua Cai1Ning Ma2Wenzhuan Xie3Chan Gao4Mengli Huang5Yuezong Bai6Yangpeng Ni7Yunqiang Tang8Department of Gastroenterological Surgery and Hernia Center, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Supported by National Key Clinical Discipline, Guangzhou, ChinaDepartment of Oncology, The Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Gastroenterological Surgery and Hernia Center, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Supported by National Key Clinical Discipline, Guangzhou, ChinaThe Medical Department, 3D Medicines Inc., Shanghai, ChinaThe Medical Department, 3D Medicines Inc., Shanghai, ChinaThe Medical Department, 3D Medicines Inc., Shanghai, ChinaThe Medical Department, 3D Medicines Inc., Shanghai, ChinaDepartment of Oncology, Jieyang People’s Hospital, Sun Yat-sen University, Jieyang, ChinaDepartment of Hepatic-Biliary Surgery, The Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, ChinaHepatocellular carcinoma (HCC) has a dismal long-term outcome. We aimed to construct a multi-gene model for prognosis prediction to inform HCC management. The cancer-specific differentially expressed genes (DEGs) were identified using RNA-seq data of paired tumor and normal tissue. A prognostic signature was built by LASSO regression analysis. Gene set enrichment analysis (GSEA) was performed to further understand the underlying molecular mechanisms. A 10-gene signature was constructed to stratify the TCGA and ICGC cohorts into high- and low-risk groups where prognosis was significantly worse in the high-risk group across cohorts (P < 0.001 for all). The 10-gene signature outperformed all previously reported models for both C-index and the AUCs for 1-, 3-, 5-year survival prediction (C-index, 0.84 vs 0.67 to 0.73; AUCs for 1-, 3- and 5-year OS, 0.84 vs 0.68 to 0.79, 0.81 to 0.68 to 0.80, and 0.85 vs 0.67 to 0.78, respectively). Multivariate Cox regression analysis revealed risk group and tumor stage to be independent predictors of survival in HCC. A nomogram incorporating tumor stage and signature-based risk group showed better performance for 1- and 3-year survival than for 5-year survival. GSEA revealed enrichment of pathways related to cell cycle regulation among high-risk samples and metabolic processes in the low-risk group. Our 10-gene model is robust for prognosis prediction and may help inform clinical management of HCC.https://www.frontiersin.org/article/10.3389/fcell.2020.00629/fullhepatocellular carcinomaexpressionprognosissignaturerisk stratification |
| spellingShingle | Taicheng Zhou Zhihua Cai Ning Ma Wenzhuan Xie Chan Gao Mengli Huang Yuezong Bai Yangpeng Ni Yunqiang Tang A Novel Ten-Gene Signature Predicting Prognosis in Hepatocellular Carcinoma Frontiers in Cell and Developmental Biology hepatocellular carcinoma expression prognosis signature risk stratification |
| title | A Novel Ten-Gene Signature Predicting Prognosis in Hepatocellular Carcinoma |
| title_full | A Novel Ten-Gene Signature Predicting Prognosis in Hepatocellular Carcinoma |
| title_fullStr | A Novel Ten-Gene Signature Predicting Prognosis in Hepatocellular Carcinoma |
| title_full_unstemmed | A Novel Ten-Gene Signature Predicting Prognosis in Hepatocellular Carcinoma |
| title_short | A Novel Ten-Gene Signature Predicting Prognosis in Hepatocellular Carcinoma |
| title_sort | novel ten gene signature predicting prognosis in hepatocellular carcinoma |
| topic | hepatocellular carcinoma expression prognosis signature risk stratification |
| url | https://www.frontiersin.org/article/10.3389/fcell.2020.00629/full |
| work_keys_str_mv | AT taichengzhou anoveltengenesignaturepredictingprognosisinhepatocellularcarcinoma AT zhihuacai anoveltengenesignaturepredictingprognosisinhepatocellularcarcinoma AT ningma anoveltengenesignaturepredictingprognosisinhepatocellularcarcinoma AT wenzhuanxie anoveltengenesignaturepredictingprognosisinhepatocellularcarcinoma AT changao anoveltengenesignaturepredictingprognosisinhepatocellularcarcinoma AT menglihuang anoveltengenesignaturepredictingprognosisinhepatocellularcarcinoma AT yuezongbai anoveltengenesignaturepredictingprognosisinhepatocellularcarcinoma AT yangpengni anoveltengenesignaturepredictingprognosisinhepatocellularcarcinoma AT yunqiangtang anoveltengenesignaturepredictingprognosisinhepatocellularcarcinoma AT taichengzhou noveltengenesignaturepredictingprognosisinhepatocellularcarcinoma AT zhihuacai noveltengenesignaturepredictingprognosisinhepatocellularcarcinoma AT ningma noveltengenesignaturepredictingprognosisinhepatocellularcarcinoma AT wenzhuanxie noveltengenesignaturepredictingprognosisinhepatocellularcarcinoma AT changao noveltengenesignaturepredictingprognosisinhepatocellularcarcinoma AT menglihuang noveltengenesignaturepredictingprognosisinhepatocellularcarcinoma AT yuezongbai noveltengenesignaturepredictingprognosisinhepatocellularcarcinoma AT yangpengni noveltengenesignaturepredictingprognosisinhepatocellularcarcinoma AT yunqiangtang noveltengenesignaturepredictingprognosisinhepatocellularcarcinoma |