Transcriptomic landscape of Hras12V oncogene-induced hepatocarcinogenesis with gender disparity
Abstract The genesis of hepatocellular carcinoma (HCC) is closely related to male factors and hyper-activated Ras signals. A transcriptomic database was established via RNA-Seq of HCC (T) and the adjacent precancerous liver tissue (P) of Hras12V transgenic mice (Ras-Tg, HCC model) and the normal liv...
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BMC
2025-01-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-025-13476-7 |
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| author | Huaiyuan Di Zhuona Rong Nan Mao Huiling Li Jun Chen Renwu Liu Aiguo Wang |
| author_facet | Huaiyuan Di Zhuona Rong Nan Mao Huiling Li Jun Chen Renwu Liu Aiguo Wang |
| author_sort | Huaiyuan Di |
| collection | DOAJ |
| description | Abstract The genesis of hepatocellular carcinoma (HCC) is closely related to male factors and hyper-activated Ras signals. A transcriptomic database was established via RNA-Seq of HCC (T) and the adjacent precancerous liver tissue (P) of Hras12V transgenic mice (Ras-Tg, HCC model) and the normal liver tissue of wild-type mice (W) of both sexes. Comparative analysis within W, P, and T and correlation expression pattern analysis revealed common/unique cluster-enriched items towards HCC between the sexes. Specifically, the numbers of differentially expressed genes (DEGs) were much higher in females than in males, and tumor suppressor genes, such as p21 Waf1/Cip1 and C6, were significantly higher in the female P. This finding denotes the higher sensitivity of female hepatocytes to the Ras oncogene and, therefore, the difficulty in developing HCC. Moreover, convergence in HCC between the sexes suggests the underlying mechanisms for the ineffectiveness of sex hormone therapies. Additionally, expression pattern analysis revealed that the DEGs and their relevant pathways were either positively or negatively associated with the HCC/Ras oncogene. Among them, the vital role of glutathione metabolism in HCC was established. This work provides a basis for future research on elucidating the underlying mechanisms, selecting the diagnostic biomarker, and planning the clinical therapy in HCC. |
| format | Article |
| id | doaj-art-097c3eb6e9ae4a879a79b4ae6113854f |
| institution | Kabale University |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj-art-097c3eb6e9ae4a879a79b4ae6113854f2025-01-19T12:26:43ZengBMCBMC Cancer1471-24072025-01-0125111610.1186/s12885-025-13476-7Transcriptomic landscape of Hras12V oncogene-induced hepatocarcinogenesis with gender disparityHuaiyuan Di0Zhuona Rong1Nan Mao2Huiling Li3Jun Chen4Renwu Liu5Aiguo Wang6Department of Comparative Medicine, Laboratory Animal Center, Dalian Medical UniversityDepartment of Comparative Medicine, Laboratory Animal Center, Dalian Medical UniversityDepartment of Comparative Medicine, Laboratory Animal Center, Dalian Medical UniversityDepartment of Comparative Medicine, Laboratory Animal Center, Dalian Medical UniversityDepartment of Comparative Medicine, Laboratory Animal Center, Dalian Medical UniversityCentral Hospital of Dalian, University of TechnologyDepartment of Comparative Medicine, Laboratory Animal Center, Dalian Medical UniversityAbstract The genesis of hepatocellular carcinoma (HCC) is closely related to male factors and hyper-activated Ras signals. A transcriptomic database was established via RNA-Seq of HCC (T) and the adjacent precancerous liver tissue (P) of Hras12V transgenic mice (Ras-Tg, HCC model) and the normal liver tissue of wild-type mice (W) of both sexes. Comparative analysis within W, P, and T and correlation expression pattern analysis revealed common/unique cluster-enriched items towards HCC between the sexes. Specifically, the numbers of differentially expressed genes (DEGs) were much higher in females than in males, and tumor suppressor genes, such as p21 Waf1/Cip1 and C6, were significantly higher in the female P. This finding denotes the higher sensitivity of female hepatocytes to the Ras oncogene and, therefore, the difficulty in developing HCC. Moreover, convergence in HCC between the sexes suggests the underlying mechanisms for the ineffectiveness of sex hormone therapies. Additionally, expression pattern analysis revealed that the DEGs and their relevant pathways were either positively or negatively associated with the HCC/Ras oncogene. Among them, the vital role of glutathione metabolism in HCC was established. This work provides a basis for future research on elucidating the underlying mechanisms, selecting the diagnostic biomarker, and planning the clinical therapy in HCC.https://doi.org/10.1186/s12885-025-13476-7Hepatocellular carcinomaTranscriptomeRas oncogeneSex disparity |
| spellingShingle | Huaiyuan Di Zhuona Rong Nan Mao Huiling Li Jun Chen Renwu Liu Aiguo Wang Transcriptomic landscape of Hras12V oncogene-induced hepatocarcinogenesis with gender disparity BMC Cancer Hepatocellular carcinoma Transcriptome Ras oncogene Sex disparity |
| title | Transcriptomic landscape of Hras12V oncogene-induced hepatocarcinogenesis with gender disparity |
| title_full | Transcriptomic landscape of Hras12V oncogene-induced hepatocarcinogenesis with gender disparity |
| title_fullStr | Transcriptomic landscape of Hras12V oncogene-induced hepatocarcinogenesis with gender disparity |
| title_full_unstemmed | Transcriptomic landscape of Hras12V oncogene-induced hepatocarcinogenesis with gender disparity |
| title_short | Transcriptomic landscape of Hras12V oncogene-induced hepatocarcinogenesis with gender disparity |
| title_sort | transcriptomic landscape of hras12v oncogene induced hepatocarcinogenesis with gender disparity |
| topic | Hepatocellular carcinoma Transcriptome Ras oncogene Sex disparity |
| url | https://doi.org/10.1186/s12885-025-13476-7 |
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