Identifying Apoptosis-Related Transcriptomic Aberrations and Revealing Clinical Relevance as Diagnostic and Prognostic Biomarker in Hepatocellular Carcinoma
In view of the unsatisfactory treatment outcome of liver cancer under current treatment, where the mortality rate is high and the survival rate is poor, in this study we aimed to use RNA sequencing data to explore potential molecular markers that can be more effective in predicting diagnosis and pro...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2020.519180/full |
| _version_ | 1828889542367641600 |
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| author | Jinyu Zhu Jinyu Zhu Bufu Tang Bufu Tang Xiuling Lv Miaomiao Meng Qiaoyou Weng Qiaoyou Weng Nannan Zhang Nannan Zhang Jie Li Jie Li Kai Fan Kai Fan Liyun Zheng Liyun Zheng Shiji Fang Shiji Fang Min Xu Min Xu Jiansong Ji Jiansong Ji |
| author_facet | Jinyu Zhu Jinyu Zhu Bufu Tang Bufu Tang Xiuling Lv Miaomiao Meng Qiaoyou Weng Qiaoyou Weng Nannan Zhang Nannan Zhang Jie Li Jie Li Kai Fan Kai Fan Liyun Zheng Liyun Zheng Shiji Fang Shiji Fang Min Xu Min Xu Jiansong Ji Jiansong Ji |
| author_sort | Jinyu Zhu |
| collection | DOAJ |
| description | In view of the unsatisfactory treatment outcome of liver cancer under current treatment, where the mortality rate is high and the survival rate is poor, in this study we aimed to use RNA sequencing data to explore potential molecular markers that can be more effective in predicting diagnosis and prognosis of hepatocellular carcinoma. RNA sequencing data and corresponding clinical information were obtained from multiple databases. After matching with the apoptotic genes from the Deathbase database, 14 differentially expressed human apoptosis genes were obtained. Using univariate and multivariate Cox regression analyses, two apoptosis genes (BAK1 and CSE1L) were determined to be closely associated with overall survival (OS) in HCC patients. And subsequently experiments also validated that knockdown of BAK1 and CSE1L significantly inhibited cell proliferation and promoted apoptosis in the HCC. Then the two genes were used to construct a prognostic signature and diagnostic models. The high-risk group showed lower OS time compared to low-risk group in the TCGA cohort (P < 0.001, HR = 2.11), GSE14520 cohort (P = 0.003, HR = 1.85), and ICGC cohort (P < 0.001, HR = 4). And the advanced HCC patients showed higher risk score and worse prognosis compared to early-stage HCC patients. Moreover, the prognostic signature was validated to be an independent prognostic factor. The diagnostic models accurately predicted HCC from normal tissues and dysplastic nodules in the training and validation cohort. These results indicated that the two apoptosis-related signature effectively predicted diagnosis and prognosis of HCC and may serve as a potential biomarker and therapeutic target for HCC. |
| first_indexed | 2024-12-13T12:42:23Z |
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| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-13T12:42:23Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-6d5b4a924e4c4b36af83cd564edf4a012022-12-21T23:45:35ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-02-011010.3389/fonc.2020.519180519180Identifying Apoptosis-Related Transcriptomic Aberrations and Revealing Clinical Relevance as Diagnostic and Prognostic Biomarker in Hepatocellular CarcinomaJinyu Zhu0Jinyu Zhu1Bufu Tang2Bufu Tang3Xiuling Lv4Miaomiao Meng5Qiaoyou Weng6Qiaoyou Weng7Nannan Zhang8Nannan Zhang9Jie Li10Jie Li11Kai Fan12Kai Fan13Liyun Zheng14Liyun Zheng15Shiji Fang16Shiji Fang17Min Xu18Min Xu19Jiansong Ji20Jiansong Ji21Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital, School of Medicine, Zhejiang University, Lishui, ChinaDepartment of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaKey Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital, School of Medicine, Zhejiang University, Lishui, ChinaDepartment of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Radiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, ChinaDepartment of Radiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, ChinaKey Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital, School of Medicine, Zhejiang University, Lishui, ChinaDepartment of Radiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, ChinaKey Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital, School of Medicine, Zhejiang University, Lishui, ChinaDepartment of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaKey Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital, School of Medicine, Zhejiang University, Lishui, ChinaDepartment of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaKey Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital, School of Medicine, Zhejiang University, Lishui, ChinaDepartment of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaKey Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital, School of Medicine, Zhejiang University, Lishui, ChinaDepartment of Radiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, ChinaKey Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital, School of Medicine, Zhejiang University, Lishui, ChinaDepartment of Radiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, ChinaKey Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital, School of Medicine, Zhejiang University, Lishui, ChinaDepartment of Radiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, ChinaKey Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital, School of Medicine, Zhejiang University, Lishui, ChinaDepartment of Radiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, ChinaIn view of the unsatisfactory treatment outcome of liver cancer under current treatment, where the mortality rate is high and the survival rate is poor, in this study we aimed to use RNA sequencing data to explore potential molecular markers that can be more effective in predicting diagnosis and prognosis of hepatocellular carcinoma. RNA sequencing data and corresponding clinical information were obtained from multiple databases. After matching with the apoptotic genes from the Deathbase database, 14 differentially expressed human apoptosis genes were obtained. Using univariate and multivariate Cox regression analyses, two apoptosis genes (BAK1 and CSE1L) were determined to be closely associated with overall survival (OS) in HCC patients. And subsequently experiments also validated that knockdown of BAK1 and CSE1L significantly inhibited cell proliferation and promoted apoptosis in the HCC. Then the two genes were used to construct a prognostic signature and diagnostic models. The high-risk group showed lower OS time compared to low-risk group in the TCGA cohort (P < 0.001, HR = 2.11), GSE14520 cohort (P = 0.003, HR = 1.85), and ICGC cohort (P < 0.001, HR = 4). And the advanced HCC patients showed higher risk score and worse prognosis compared to early-stage HCC patients. Moreover, the prognostic signature was validated to be an independent prognostic factor. The diagnostic models accurately predicted HCC from normal tissues and dysplastic nodules in the training and validation cohort. These results indicated that the two apoptosis-related signature effectively predicted diagnosis and prognosis of HCC and may serve as a potential biomarker and therapeutic target for HCC.https://www.frontiersin.org/articles/10.3389/fonc.2020.519180/fullapoptosishepatocellular carcinomaoverall survivalrelapse-free survivaldiagnosisprognosis |
| spellingShingle | Jinyu Zhu Jinyu Zhu Bufu Tang Bufu Tang Xiuling Lv Miaomiao Meng Qiaoyou Weng Qiaoyou Weng Nannan Zhang Nannan Zhang Jie Li Jie Li Kai Fan Kai Fan Liyun Zheng Liyun Zheng Shiji Fang Shiji Fang Min Xu Min Xu Jiansong Ji Jiansong Ji Identifying Apoptosis-Related Transcriptomic Aberrations and Revealing Clinical Relevance as Diagnostic and Prognostic Biomarker in Hepatocellular Carcinoma Frontiers in Oncology apoptosis hepatocellular carcinoma overall survival relapse-free survival diagnosis prognosis |
| title | Identifying Apoptosis-Related Transcriptomic Aberrations and Revealing Clinical Relevance as Diagnostic and Prognostic Biomarker in Hepatocellular Carcinoma |
| title_full | Identifying Apoptosis-Related Transcriptomic Aberrations and Revealing Clinical Relevance as Diagnostic and Prognostic Biomarker in Hepatocellular Carcinoma |
| title_fullStr | Identifying Apoptosis-Related Transcriptomic Aberrations and Revealing Clinical Relevance as Diagnostic and Prognostic Biomarker in Hepatocellular Carcinoma |
| title_full_unstemmed | Identifying Apoptosis-Related Transcriptomic Aberrations and Revealing Clinical Relevance as Diagnostic and Prognostic Biomarker in Hepatocellular Carcinoma |
| title_short | Identifying Apoptosis-Related Transcriptomic Aberrations and Revealing Clinical Relevance as Diagnostic and Prognostic Biomarker in Hepatocellular Carcinoma |
| title_sort | identifying apoptosis related transcriptomic aberrations and revealing clinical relevance as diagnostic and prognostic biomarker in hepatocellular carcinoma |
| topic | apoptosis hepatocellular carcinoma overall survival relapse-free survival diagnosis prognosis |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2020.519180/full |
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