Predicting hepatocellular carcinoma outcomes and immune therapy response with ATP-dependent chromatin remodeling-related genes, highlighting MORF4L1 as a promising target
Abstract Background Hepatocellular carcinoma (HCC) continues to be a major cause of cancer-related death worldwide, primarily due to delays in diagnosis and resistance to existing treatments. Recent research has identified ATP-dependent chromatin remodeling-related genes (ACRRGs) as promising target...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12935-024-03629-2 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841544286562156544 |
|---|---|
| author | Chao Xu Litao Liang Guoqing Liu Yanzhi Feng Bin Xu Deming Zhu Wenbo Jia Jinyi Wang Wenhu Zhao Xiangyu Ling Yongping Zhou Wenzhou Ding Lianbao Kong |
| author_facet | Chao Xu Litao Liang Guoqing Liu Yanzhi Feng Bin Xu Deming Zhu Wenbo Jia Jinyi Wang Wenhu Zhao Xiangyu Ling Yongping Zhou Wenzhou Ding Lianbao Kong |
| author_sort | Chao Xu |
| collection | DOAJ |
| description | Abstract Background Hepatocellular carcinoma (HCC) continues to be a major cause of cancer-related death worldwide, primarily due to delays in diagnosis and resistance to existing treatments. Recent research has identified ATP-dependent chromatin remodeling-related genes (ACRRGs) as promising targets for therapeutic intervention across various types of cancer. This development offers potential new avenues for addressing the challenges in HCC management. Methods This study integrated bioinformatics analyses and experimental approaches to explore the role of ACRRGs in HCC. We utilized data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), applying machine learning algorithms to develop a prognostic model based on ACRRGs’ expression. Experimental validation was conducted using quantitative real-time Polymerase Chain Reaction (qRT-PCR), Western blotting, and functional assays in HCC cell lines and xenograft models. Results Our bioinformatics analysis identified four key ACRRGs—MORF4L1, HDAC1, VPS72, and RUVBL2—that serve as prognostic markers for HCC. The developed risk prediction model effectively distinguished between high-risk and low-risk patients, showing significant differences in survival outcomes and predicting responses to immunotherapy in HCC patients. Experimentally, MORF4L1 was demonstrated to enhance cancer stemness by activating the Hedgehog signaling pathway, as supported by both in vitro and in vivo assays. Conclusion ACRRGs, particularly MORF4L1, play crucial roles in modulating HCC progression, offering new insights into the molecular mechanisms driving HCC and potential therapeutic targets. Our findings advocate for the inclusion of chromatin remodeling dynamics in the strategic development of precision therapies for HCC. |
| format | Article |
| id | doaj-art-702b408f6ea54184abfd8a938b15c4a1 |
| institution | Kabale University |
| issn | 1475-2867 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj-art-702b408f6ea54184abfd8a938b15c4a12025-01-12T12:40:41ZengBMCCancer Cell International1475-28672025-01-0125111710.1186/s12935-024-03629-2Predicting hepatocellular carcinoma outcomes and immune therapy response with ATP-dependent chromatin remodeling-related genes, highlighting MORF4L1 as a promising targetChao Xu0Litao Liang1Guoqing Liu2Yanzhi Feng3Bin Xu4Deming Zhu5Wenbo Jia6Jinyi Wang7Wenhu Zhao8Xiangyu Ling9Yongping Zhou10Wenzhou Ding11Lianbao Kong12Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Hepatobiliary CancersHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Hepatobiliary CancersChildren’s Hospital of Nanjing Medical UniversityHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Hepatobiliary CancersDepartment of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Qingdao UniversityHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Hepatobiliary CancersHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Hepatobiliary CancersHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Hepatobiliary CancersHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Hepatobiliary CancersHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Hepatobiliary CancersDepartment of Hepatobiliary Surgery, Wuxi No.2 People’s HospitalHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Hepatobiliary CancersHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Hepatobiliary CancersAbstract Background Hepatocellular carcinoma (HCC) continues to be a major cause of cancer-related death worldwide, primarily due to delays in diagnosis and resistance to existing treatments. Recent research has identified ATP-dependent chromatin remodeling-related genes (ACRRGs) as promising targets for therapeutic intervention across various types of cancer. This development offers potential new avenues for addressing the challenges in HCC management. Methods This study integrated bioinformatics analyses and experimental approaches to explore the role of ACRRGs in HCC. We utilized data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), applying machine learning algorithms to develop a prognostic model based on ACRRGs’ expression. Experimental validation was conducted using quantitative real-time Polymerase Chain Reaction (qRT-PCR), Western blotting, and functional assays in HCC cell lines and xenograft models. Results Our bioinformatics analysis identified four key ACRRGs—MORF4L1, HDAC1, VPS72, and RUVBL2—that serve as prognostic markers for HCC. The developed risk prediction model effectively distinguished between high-risk and low-risk patients, showing significant differences in survival outcomes and predicting responses to immunotherapy in HCC patients. Experimentally, MORF4L1 was demonstrated to enhance cancer stemness by activating the Hedgehog signaling pathway, as supported by both in vitro and in vivo assays. Conclusion ACRRGs, particularly MORF4L1, play crucial roles in modulating HCC progression, offering new insights into the molecular mechanisms driving HCC and potential therapeutic targets. Our findings advocate for the inclusion of chromatin remodeling dynamics in the strategic development of precision therapies for HCC.https://doi.org/10.1186/s12935-024-03629-2ATP-dependent chromatin remodelingHepatocellular carcinomaCancer stem cellsImmunotherapy |
| spellingShingle | Chao Xu Litao Liang Guoqing Liu Yanzhi Feng Bin Xu Deming Zhu Wenbo Jia Jinyi Wang Wenhu Zhao Xiangyu Ling Yongping Zhou Wenzhou Ding Lianbao Kong Predicting hepatocellular carcinoma outcomes and immune therapy response with ATP-dependent chromatin remodeling-related genes, highlighting MORF4L1 as a promising target Cancer Cell International ATP-dependent chromatin remodeling Hepatocellular carcinoma Cancer stem cells Immunotherapy |
| title | Predicting hepatocellular carcinoma outcomes and immune therapy response with ATP-dependent chromatin remodeling-related genes, highlighting MORF4L1 as a promising target |
| title_full | Predicting hepatocellular carcinoma outcomes and immune therapy response with ATP-dependent chromatin remodeling-related genes, highlighting MORF4L1 as a promising target |
| title_fullStr | Predicting hepatocellular carcinoma outcomes and immune therapy response with ATP-dependent chromatin remodeling-related genes, highlighting MORF4L1 as a promising target |
| title_full_unstemmed | Predicting hepatocellular carcinoma outcomes and immune therapy response with ATP-dependent chromatin remodeling-related genes, highlighting MORF4L1 as a promising target |
| title_short | Predicting hepatocellular carcinoma outcomes and immune therapy response with ATP-dependent chromatin remodeling-related genes, highlighting MORF4L1 as a promising target |
| title_sort | predicting hepatocellular carcinoma outcomes and immune therapy response with atp dependent chromatin remodeling related genes highlighting morf4l1 as a promising target |
| topic | ATP-dependent chromatin remodeling Hepatocellular carcinoma Cancer stem cells Immunotherapy |
| url | https://doi.org/10.1186/s12935-024-03629-2 |
| work_keys_str_mv | AT chaoxu predictinghepatocellularcarcinomaoutcomesandimmunetherapyresponsewithatpdependentchromatinremodelingrelatedgeneshighlightingmorf4l1asapromisingtarget AT litaoliang predictinghepatocellularcarcinomaoutcomesandimmunetherapyresponsewithatpdependentchromatinremodelingrelatedgeneshighlightingmorf4l1asapromisingtarget AT guoqingliu predictinghepatocellularcarcinomaoutcomesandimmunetherapyresponsewithatpdependentchromatinremodelingrelatedgeneshighlightingmorf4l1asapromisingtarget AT yanzhifeng predictinghepatocellularcarcinomaoutcomesandimmunetherapyresponsewithatpdependentchromatinremodelingrelatedgeneshighlightingmorf4l1asapromisingtarget AT binxu predictinghepatocellularcarcinomaoutcomesandimmunetherapyresponsewithatpdependentchromatinremodelingrelatedgeneshighlightingmorf4l1asapromisingtarget AT demingzhu predictinghepatocellularcarcinomaoutcomesandimmunetherapyresponsewithatpdependentchromatinremodelingrelatedgeneshighlightingmorf4l1asapromisingtarget AT wenbojia predictinghepatocellularcarcinomaoutcomesandimmunetherapyresponsewithatpdependentchromatinremodelingrelatedgeneshighlightingmorf4l1asapromisingtarget AT jinyiwang predictinghepatocellularcarcinomaoutcomesandimmunetherapyresponsewithatpdependentchromatinremodelingrelatedgeneshighlightingmorf4l1asapromisingtarget AT wenhuzhao predictinghepatocellularcarcinomaoutcomesandimmunetherapyresponsewithatpdependentchromatinremodelingrelatedgeneshighlightingmorf4l1asapromisingtarget AT xiangyuling predictinghepatocellularcarcinomaoutcomesandimmunetherapyresponsewithatpdependentchromatinremodelingrelatedgeneshighlightingmorf4l1asapromisingtarget AT yongpingzhou predictinghepatocellularcarcinomaoutcomesandimmunetherapyresponsewithatpdependentchromatinremodelingrelatedgeneshighlightingmorf4l1asapromisingtarget AT wenzhouding predictinghepatocellularcarcinomaoutcomesandimmunetherapyresponsewithatpdependentchromatinremodelingrelatedgeneshighlightingmorf4l1asapromisingtarget AT lianbaokong predictinghepatocellularcarcinomaoutcomesandimmunetherapyresponsewithatpdependentchromatinremodelingrelatedgeneshighlightingmorf4l1asapromisingtarget |