The Mutational and Transcriptional Landscapes of Hepatocarcinogenesis in a Rat Model
Summary: Hepatocellular carcinoma (HCC) initiation is characterized by stepwise accumulation of molecular alterations, during which the early events are largely unknown. Here, we presented a comprehensive genomic and transcriptomic landscape at stages of hepatitis, cirrhosis, and HCC by using a diet...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-11-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004220308828 |
| _version_ | 1818457376181714944 |
|---|---|
| author | Zhiao Chen Shengli Li Mengting Shen Xinyuan Lu Chunyang Bao Di Chen Jie Ding Qifeng Wang Shenglin Huang Wenming Cong Leng Han Xianghuo He |
| author_facet | Zhiao Chen Shengli Li Mengting Shen Xinyuan Lu Chunyang Bao Di Chen Jie Ding Qifeng Wang Shenglin Huang Wenming Cong Leng Han Xianghuo He |
| author_sort | Zhiao Chen |
| collection | DOAJ |
| description | Summary: Hepatocellular carcinoma (HCC) initiation is characterized by stepwise accumulation of molecular alterations, during which the early events are largely unknown. Here, we presented a comprehensive genomic and transcriptomic landscape at stages of hepatitis, cirrhosis, and HCC by using a diethylnitrosamine-induced rat HCC model. We observed the early occurrence of gene instability and aberrant cancer associated signaling pathways in liver hepatitis. We further characterized the progressive molecular changes during hepatocarcinogenesis, wherein the intense rivalry between tumor-suppressive and oncogenic strengths occurred in cirrhosis stage. Despite the significant pathological difference, mutation signatures and expression landscape are highly similar between hepatitis and cirrhosis stages. Furthermore, we identified PI3K-Akt signaling pathway as a key pathway in the process of hepatocarcinogenesis through integrative analysis, and PIK3CD is a potential biomarker indicating HCC recurrence. The dynamic immune response during hepatocarcinogenesis, such as continuous decline of monocytes, suggests an immunological intervention strategy beyond chemoprevention for liver cancer. |
| first_indexed | 2024-12-14T22:41:35Z |
| format | Article |
| id | doaj.art-2c0c48055c2f4a87874a4e794d233297 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-14T22:41:35Z |
| publishDate | 2020-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-2c0c48055c2f4a87874a4e794d2332972022-12-21T22:44:58ZengElsevieriScience2589-00422020-11-012311101690The Mutational and Transcriptional Landscapes of Hepatocarcinogenesis in a Rat ModelZhiao Chen0Shengli Li1Mengting Shen2Xinyuan Lu3Chunyang Bao4Di Chen5Jie Ding6Qifeng Wang7Shenglin Huang8Wenming Cong9Leng Han10Xianghuo He11Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaDepartment of Biochemistry and Molecular Biology, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, ChinaFudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaDepartment of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, ChinaFudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaFudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaFudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaFudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaFudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaDepartment of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, ChinaDepartment of Biochemistry and Molecular Biology, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Corresponding authorFudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China; Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China; Corresponding authorSummary: Hepatocellular carcinoma (HCC) initiation is characterized by stepwise accumulation of molecular alterations, during which the early events are largely unknown. Here, we presented a comprehensive genomic and transcriptomic landscape at stages of hepatitis, cirrhosis, and HCC by using a diethylnitrosamine-induced rat HCC model. We observed the early occurrence of gene instability and aberrant cancer associated signaling pathways in liver hepatitis. We further characterized the progressive molecular changes during hepatocarcinogenesis, wherein the intense rivalry between tumor-suppressive and oncogenic strengths occurred in cirrhosis stage. Despite the significant pathological difference, mutation signatures and expression landscape are highly similar between hepatitis and cirrhosis stages. Furthermore, we identified PI3K-Akt signaling pathway as a key pathway in the process of hepatocarcinogenesis through integrative analysis, and PIK3CD is a potential biomarker indicating HCC recurrence. The dynamic immune response during hepatocarcinogenesis, such as continuous decline of monocytes, suggests an immunological intervention strategy beyond chemoprevention for liver cancer.http://www.sciencedirect.com/science/article/pii/S2589004220308828GenomicsCancer Systems BiologyCancerTranscriptomics |
| spellingShingle | Zhiao Chen Shengli Li Mengting Shen Xinyuan Lu Chunyang Bao Di Chen Jie Ding Qifeng Wang Shenglin Huang Wenming Cong Leng Han Xianghuo He The Mutational and Transcriptional Landscapes of Hepatocarcinogenesis in a Rat Model iScience Genomics Cancer Systems Biology Cancer Transcriptomics |
| title | The Mutational and Transcriptional Landscapes of Hepatocarcinogenesis in a Rat Model |
| title_full | The Mutational and Transcriptional Landscapes of Hepatocarcinogenesis in a Rat Model |
| title_fullStr | The Mutational and Transcriptional Landscapes of Hepatocarcinogenesis in a Rat Model |
| title_full_unstemmed | The Mutational and Transcriptional Landscapes of Hepatocarcinogenesis in a Rat Model |
| title_short | The Mutational and Transcriptional Landscapes of Hepatocarcinogenesis in a Rat Model |
| title_sort | mutational and transcriptional landscapes of hepatocarcinogenesis in a rat model |
| topic | Genomics Cancer Systems Biology Cancer Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004220308828 |
| work_keys_str_mv | AT zhiaochen themutationalandtranscriptionallandscapesofhepatocarcinogenesisinaratmodel AT shenglili themutationalandtranscriptionallandscapesofhepatocarcinogenesisinaratmodel AT mengtingshen themutationalandtranscriptionallandscapesofhepatocarcinogenesisinaratmodel AT xinyuanlu themutationalandtranscriptionallandscapesofhepatocarcinogenesisinaratmodel AT chunyangbao themutationalandtranscriptionallandscapesofhepatocarcinogenesisinaratmodel AT dichen themutationalandtranscriptionallandscapesofhepatocarcinogenesisinaratmodel AT jieding themutationalandtranscriptionallandscapesofhepatocarcinogenesisinaratmodel AT qifengwang themutationalandtranscriptionallandscapesofhepatocarcinogenesisinaratmodel AT shenglinhuang themutationalandtranscriptionallandscapesofhepatocarcinogenesisinaratmodel AT wenmingcong themutationalandtranscriptionallandscapesofhepatocarcinogenesisinaratmodel AT lenghan themutationalandtranscriptionallandscapesofhepatocarcinogenesisinaratmodel AT xianghuohe themutationalandtranscriptionallandscapesofhepatocarcinogenesisinaratmodel AT zhiaochen mutationalandtranscriptionallandscapesofhepatocarcinogenesisinaratmodel AT shenglili mutationalandtranscriptionallandscapesofhepatocarcinogenesisinaratmodel AT mengtingshen mutationalandtranscriptionallandscapesofhepatocarcinogenesisinaratmodel AT xinyuanlu mutationalandtranscriptionallandscapesofhepatocarcinogenesisinaratmodel AT chunyangbao mutationalandtranscriptionallandscapesofhepatocarcinogenesisinaratmodel AT dichen mutationalandtranscriptionallandscapesofhepatocarcinogenesisinaratmodel AT jieding mutationalandtranscriptionallandscapesofhepatocarcinogenesisinaratmodel AT qifengwang mutationalandtranscriptionallandscapesofhepatocarcinogenesisinaratmodel AT shenglinhuang mutationalandtranscriptionallandscapesofhepatocarcinogenesisinaratmodel AT wenmingcong mutationalandtranscriptionallandscapesofhepatocarcinogenesisinaratmodel AT lenghan mutationalandtranscriptionallandscapesofhepatocarcinogenesisinaratmodel AT xianghuohe mutationalandtranscriptionallandscapesofhepatocarcinogenesisinaratmodel |