A Comprehensive Study Employing Computational Analysis and Mendelian Randomization Has Revealed the Impact of Key Genes on Liver Cancer
<b>Background and Aims</b>: In this research, we sought to enhance our comprehension of liver cancer’s genetic architecture by employing Mendelian randomization (MR) techniques to establish causative relationships between particular genetic variations and liver cancer susceptibility. <...
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2025-05-01
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| author | Size Li Wenying Qi Junzheng Wu Chunhua Luo Shihao Zheng Xu Cao Wei Wang Qiyao Liu Hongbo Du Xiaoke Li Xiaobin Zao Yongan Ye |
| author_facet | Size Li Wenying Qi Junzheng Wu Chunhua Luo Shihao Zheng Xu Cao Wei Wang Qiyao Liu Hongbo Du Xiaoke Li Xiaobin Zao Yongan Ye |
| author_sort | Size Li |
| collection | DOAJ |
| description | <b>Background and Aims</b>: In this research, we sought to enhance our comprehension of liver cancer’s genetic architecture by employing Mendelian randomization (MR) techniques to establish causative relationships between particular genetic variations and liver cancer susceptibility. <b>Methods</b>: We integrated data from the public databases with MR analysis to identify differentially expressed genes (DEGs) associated with Hepatocellular Carcinoma (HCC). We conducted functional enrichment analyses to determine the biological processes and signaling cascades associated with the identified DEGs. We also used the CIBERSORT deconvolution method to evaluate immune cell composition in HCC tissues, followed by correlation studies examining relationships between our key genes of interest and various immune cell populations. Additionally, we validated our findings using a rat model of HCC and clinical HCC samples. <b>Results</b>: We obtained two key genes, <i>EHD4</i> and <i>PPARGC1A</i>, which co-regulated M0 macrophages, suggesting their role in macrophage polarization and tumor progression. In addition, <i>PPARGC1A</i> is associated with resting and activated mast cells, suggesting its involvement in regulating the tumor microenvironment. Detection of rat and clinical samples further confirmed the upregulation of these genes in HCC, supporting their potential as therapeutic targets. <b>Conclusions</b>: Our findings emphasize the significant involvement of <i>EHD4</i> and <i>PPARGC1A</i> in HCC, specifically regarding their influence on tumor-associated macrophage polarization and broader immune microenvironment modulation. These findings offer new insights into the molecular mechanisms driving HCC and suggest that targeting these genes may provide novel strategies for personalized treatment. |
| format | Article |
| id | doaj-art-3968d67da147439f8d709749fedb6095 |
| institution | Kabale University |
| issn | 2227-9059 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj-art-3968d67da147439f8d709749fedb60952025-08-20T03:26:49ZengMDPI AGBiomedicines2227-90592025-05-01136131310.3390/biomedicines13061313A Comprehensive Study Employing Computational Analysis and Mendelian Randomization Has Revealed the Impact of Key Genes on Liver CancerSize Li0Wenying Qi1Junzheng Wu2Chunhua Luo3Shihao Zheng4Xu Cao5Wei Wang6Qiyao Liu7Hongbo Du8Xiaoke Li9Xiaobin Zao10Yongan Ye11Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, ChinaDongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, ChinaXiamen Hospital of Traditional Chinese Medicine, Xiamen 361006, ChinaXiamen Hospital of Traditional Chinese Medicine, Xiamen 361006, ChinaDongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, ChinaDongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, ChinaDongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, ChinaDongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, ChinaDongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, ChinaDongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, ChinaDongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, ChinaDongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China<b>Background and Aims</b>: In this research, we sought to enhance our comprehension of liver cancer’s genetic architecture by employing Mendelian randomization (MR) techniques to establish causative relationships between particular genetic variations and liver cancer susceptibility. <b>Methods</b>: We integrated data from the public databases with MR analysis to identify differentially expressed genes (DEGs) associated with Hepatocellular Carcinoma (HCC). We conducted functional enrichment analyses to determine the biological processes and signaling cascades associated with the identified DEGs. We also used the CIBERSORT deconvolution method to evaluate immune cell composition in HCC tissues, followed by correlation studies examining relationships between our key genes of interest and various immune cell populations. Additionally, we validated our findings using a rat model of HCC and clinical HCC samples. <b>Results</b>: We obtained two key genes, <i>EHD4</i> and <i>PPARGC1A</i>, which co-regulated M0 macrophages, suggesting their role in macrophage polarization and tumor progression. In addition, <i>PPARGC1A</i> is associated with resting and activated mast cells, suggesting its involvement in regulating the tumor microenvironment. Detection of rat and clinical samples further confirmed the upregulation of these genes in HCC, supporting their potential as therapeutic targets. <b>Conclusions</b>: Our findings emphasize the significant involvement of <i>EHD4</i> and <i>PPARGC1A</i> in HCC, specifically regarding their influence on tumor-associated macrophage polarization and broader immune microenvironment modulation. These findings offer new insights into the molecular mechanisms driving HCC and suggest that targeting these genes may provide novel strategies for personalized treatment.https://www.mdpi.com/2227-9059/13/6/1313hepatocellular carcinomaEHD4PPARGC1AMendelian randomizationimmune cell infiltrationtumor-associated macrophages |
| spellingShingle | Size Li Wenying Qi Junzheng Wu Chunhua Luo Shihao Zheng Xu Cao Wei Wang Qiyao Liu Hongbo Du Xiaoke Li Xiaobin Zao Yongan Ye A Comprehensive Study Employing Computational Analysis and Mendelian Randomization Has Revealed the Impact of Key Genes on Liver Cancer Biomedicines hepatocellular carcinoma EHD4 PPARGC1A Mendelian randomization immune cell infiltration tumor-associated macrophages |
| title | A Comprehensive Study Employing Computational Analysis and Mendelian Randomization Has Revealed the Impact of Key Genes on Liver Cancer |
| title_full | A Comprehensive Study Employing Computational Analysis and Mendelian Randomization Has Revealed the Impact of Key Genes on Liver Cancer |
| title_fullStr | A Comprehensive Study Employing Computational Analysis and Mendelian Randomization Has Revealed the Impact of Key Genes on Liver Cancer |
| title_full_unstemmed | A Comprehensive Study Employing Computational Analysis and Mendelian Randomization Has Revealed the Impact of Key Genes on Liver Cancer |
| title_short | A Comprehensive Study Employing Computational Analysis and Mendelian Randomization Has Revealed the Impact of Key Genes on Liver Cancer |
| title_sort | comprehensive study employing computational analysis and mendelian randomization has revealed the impact of key genes on liver cancer |
| topic | hepatocellular carcinoma EHD4 PPARGC1A Mendelian randomization immune cell infiltration tumor-associated macrophages |
| url | https://www.mdpi.com/2227-9059/13/6/1313 |
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