Establishment and Validation of a Novel Risk Score for Hepatocellular Carcinoma Based on Bile Acid and Bile Salt Metabolism-Related Genes
Liver cancer is a public disease burden with an increasing incidence rate globally. Bile acid and bile salt’s metabolic pathways participate in liver tumorigenesis and regulate the tumor microenvironment. However, there still remains a lack of systematic analysis of the genes related to bile acid an...
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MDPI AG
2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/10/8597 |
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| author | Qingmiao Shi Xin Yuan Chen Xue Xinyu Gu Lanjuan Li |
| author_facet | Qingmiao Shi Xin Yuan Chen Xue Xinyu Gu Lanjuan Li |
| author_sort | Qingmiao Shi |
| collection | DOAJ |
| description | Liver cancer is a public disease burden with an increasing incidence rate globally. Bile acid and bile salt’s metabolic pathways participate in liver tumorigenesis and regulate the tumor microenvironment. However, there still remains a lack of systematic analysis of the genes related to bile acid and bile salt metabolic pathways in hepatocellular carcinoma (HCC). The mRNA expression data and clinical follow-up information of patients with HCC were obtained from public databases, including The Cancer Genome Atlas, Hepatocellular Carcinoma Database, Gene Expression Omnibus, and IMvigor210. The bile acid and bile salt metabolism-related genes were extracted from Molecular Signatures Database. Univariate Cox and logistic least absolute shrinkage and selection operator regression analyses were conducted to establish the risk model. Single sample gene set enrichment analysis, Estimation of STromal and Immune cells in MAlignant Tumour tissues using Expression data, and Tumor Immune Dysfunction and Exclusion were adopted to analyze immune status. The efficiency of the risk model was tested using a decision tree and a nomogram. We determined two molecular subtypes based on bile acid and bile salt metabolism-related genes, with the prognosis of the S1 subtype being markedly superior to the S2 subtype. Next, we established a risk model based on the differentially expressed genes between the two molecular subtypes. The high-risk and low-risk groups showed significant differences in the biological pathways, immune score, immunotherapy response, and drug susceptibility. Our results demonstrated the good predictive performance of the risk model in immunotherapy datasets and established that it could be an essential factor affecting the prognosis of HCC. In conclusion, we identified two molecular subtypes based on bile acid and bile salt metabolism-related genes. The risk model established in our study could effectively predict the prognosis of patients with HCC and their immunotherapeutic response, which may contribute to targeted immunotherapy in HCC. |
| first_indexed | 2024-03-11T03:40:43Z |
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| id | doaj.art-951cbdb3a151407a9c0e9158d1f10668 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T03:40:43Z |
| publishDate | 2023-05-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-951cbdb3a151407a9c0e9158d1f106682023-11-18T01:38:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012410859710.3390/ijms24108597Establishment and Validation of a Novel Risk Score for Hepatocellular Carcinoma Based on Bile Acid and Bile Salt Metabolism-Related GenesQingmiao Shi0Xin Yuan1Chen Xue2Xinyu Gu3Lanjuan Li4State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, ChinaState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, ChinaState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, ChinaState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, ChinaState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, ChinaLiver cancer is a public disease burden with an increasing incidence rate globally. Bile acid and bile salt’s metabolic pathways participate in liver tumorigenesis and regulate the tumor microenvironment. However, there still remains a lack of systematic analysis of the genes related to bile acid and bile salt metabolic pathways in hepatocellular carcinoma (HCC). The mRNA expression data and clinical follow-up information of patients with HCC were obtained from public databases, including The Cancer Genome Atlas, Hepatocellular Carcinoma Database, Gene Expression Omnibus, and IMvigor210. The bile acid and bile salt metabolism-related genes were extracted from Molecular Signatures Database. Univariate Cox and logistic least absolute shrinkage and selection operator regression analyses were conducted to establish the risk model. Single sample gene set enrichment analysis, Estimation of STromal and Immune cells in MAlignant Tumour tissues using Expression data, and Tumor Immune Dysfunction and Exclusion were adopted to analyze immune status. The efficiency of the risk model was tested using a decision tree and a nomogram. We determined two molecular subtypes based on bile acid and bile salt metabolism-related genes, with the prognosis of the S1 subtype being markedly superior to the S2 subtype. Next, we established a risk model based on the differentially expressed genes between the two molecular subtypes. The high-risk and low-risk groups showed significant differences in the biological pathways, immune score, immunotherapy response, and drug susceptibility. Our results demonstrated the good predictive performance of the risk model in immunotherapy datasets and established that it could be an essential factor affecting the prognosis of HCC. In conclusion, we identified two molecular subtypes based on bile acid and bile salt metabolism-related genes. The risk model established in our study could effectively predict the prognosis of patients with HCC and their immunotherapeutic response, which may contribute to targeted immunotherapy in HCC.https://www.mdpi.com/1422-0067/24/10/8597hepatocellular carcinomabile acidrisk modelprognosistumor microenvironmentimmunotherapy |
| spellingShingle | Qingmiao Shi Xin Yuan Chen Xue Xinyu Gu Lanjuan Li Establishment and Validation of a Novel Risk Score for Hepatocellular Carcinoma Based on Bile Acid and Bile Salt Metabolism-Related Genes International Journal of Molecular Sciences hepatocellular carcinoma bile acid risk model prognosis tumor microenvironment immunotherapy |
| title | Establishment and Validation of a Novel Risk Score for Hepatocellular Carcinoma Based on Bile Acid and Bile Salt Metabolism-Related Genes |
| title_full | Establishment and Validation of a Novel Risk Score for Hepatocellular Carcinoma Based on Bile Acid and Bile Salt Metabolism-Related Genes |
| title_fullStr | Establishment and Validation of a Novel Risk Score for Hepatocellular Carcinoma Based on Bile Acid and Bile Salt Metabolism-Related Genes |
| title_full_unstemmed | Establishment and Validation of a Novel Risk Score for Hepatocellular Carcinoma Based on Bile Acid and Bile Salt Metabolism-Related Genes |
| title_short | Establishment and Validation of a Novel Risk Score for Hepatocellular Carcinoma Based on Bile Acid and Bile Salt Metabolism-Related Genes |
| title_sort | establishment and validation of a novel risk score for hepatocellular carcinoma based on bile acid and bile salt metabolism related genes |
| topic | hepatocellular carcinoma bile acid risk model prognosis tumor microenvironment immunotherapy |
| url | https://www.mdpi.com/1422-0067/24/10/8597 |
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