An exosome mRNA-related gene risk model to evaluate the tumor microenvironment and predict prognosis in hepatocellular carcinoma
Abstract Background The interplay between exosomes and the tumor microenvironment (TME) remains unclear. We investigated the influence of exosomes on the TME in hepatocellular carcinoma (HCC), focusing on their mRNA expression profile. Methods mRNA expression profiles of exosomes were obtained from...
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| Format: | Article |
| Language: | English |
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BMC
2024-04-01
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| Series: | BMC Medical Genomics |
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| Online Access: | https://doi.org/10.1186/s12920-024-01865-z |
| _version_ | 1797199127181787136 |
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| author | Zhonghai Du Xiuchen Han Liping Zhu Li Li Leandro Castellano Justin Stebbing Ling Peng Zhiqiang Wang |
| author_facet | Zhonghai Du Xiuchen Han Liping Zhu Li Li Leandro Castellano Justin Stebbing Ling Peng Zhiqiang Wang |
| author_sort | Zhonghai Du |
| collection | DOAJ |
| description | Abstract Background The interplay between exosomes and the tumor microenvironment (TME) remains unclear. We investigated the influence of exosomes on the TME in hepatocellular carcinoma (HCC), focusing on their mRNA expression profile. Methods mRNA expression profiles of exosomes were obtained from exoRBase. RNA sequencing data from HCC patients’ tumors were acquired from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). An exosome mRNA-related risk score model of prognostic value was established. The patients in the two databases were divided into high- and low-risk groups based on the median risk score value, and used to validate one another. Functional enrichment analysis was performed based on a differential gene prognosis model (DGPM). CIBERSORT was used to assess the abundance of immune cells in the TME. The correlation between the expression levels of immune checkpoint-related genes and DGPM was analyzed alongside the prediction value to drug sensitivity. Results A prognostic exosome mRNA-related 4-gene signature (DYNC1H1, PRKDC, CCDC88A, and ADAMTS5) was constructed and validated. A prognostic nomogram had prognostic ability for HCC. The genes for this model are involved in extracellular matrix, extracellular matrix (ECM)-receptor interaction, and the PI3K-Akt signaling pathway. Expression of genes here had a positive correlation with immune cell infiltration in the TME. Conclusions Our study results demonstrate that an exosome mRNA-related risk model can be established in HCC, highlighting the functional significance of the molecules in prognosis and risk stratification. |
| first_indexed | 2024-04-24T07:10:49Z |
| format | Article |
| id | doaj.art-74340b91ad8d462bbe852e8ec6175ef0 |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-04-24T07:10:49Z |
| publishDate | 2024-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genomics |
| spelling | doaj.art-74340b91ad8d462bbe852e8ec6175ef02024-04-21T11:33:18ZengBMCBMC Medical Genomics1755-87942024-04-0117111810.1186/s12920-024-01865-zAn exosome mRNA-related gene risk model to evaluate the tumor microenvironment and predict prognosis in hepatocellular carcinomaZhonghai Du0Xiuchen Han1Liping Zhu2Li Li3Leandro Castellano4Justin Stebbing5Ling Peng6Zhiqiang Wang7Department of Medical Oncology, Weifang Hospital of Traditional Chinese MedicineDepartment of Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Medical Oncology, Shouguang Hospital of Traditional Chinese MedicineOutpatient Surgery Center, Shouguang Hospital of Traditional Chinese MedicineDepartment of Biochemistry, School of Life Sciences, University of SussexDepartment of Life Sciences, Anglia Ruskin UniversityDepartment of Pulmonary and Critical Care Medicine, Cancer Center, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical CollegeDepartment of Urology, Shouguang Hospital of Traditional Chinese MedicineAbstract Background The interplay between exosomes and the tumor microenvironment (TME) remains unclear. We investigated the influence of exosomes on the TME in hepatocellular carcinoma (HCC), focusing on their mRNA expression profile. Methods mRNA expression profiles of exosomes were obtained from exoRBase. RNA sequencing data from HCC patients’ tumors were acquired from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). An exosome mRNA-related risk score model of prognostic value was established. The patients in the two databases were divided into high- and low-risk groups based on the median risk score value, and used to validate one another. Functional enrichment analysis was performed based on a differential gene prognosis model (DGPM). CIBERSORT was used to assess the abundance of immune cells in the TME. The correlation between the expression levels of immune checkpoint-related genes and DGPM was analyzed alongside the prediction value to drug sensitivity. Results A prognostic exosome mRNA-related 4-gene signature (DYNC1H1, PRKDC, CCDC88A, and ADAMTS5) was constructed and validated. A prognostic nomogram had prognostic ability for HCC. The genes for this model are involved in extracellular matrix, extracellular matrix (ECM)-receptor interaction, and the PI3K-Akt signaling pathway. Expression of genes here had a positive correlation with immune cell infiltration in the TME. Conclusions Our study results demonstrate that an exosome mRNA-related risk model can be established in HCC, highlighting the functional significance of the molecules in prognosis and risk stratification.https://doi.org/10.1186/s12920-024-01865-zHepatocellular carcinomaExtracellular vesicleExosomeRisk scorePrognostic signatureTumor immune microenvironment |
| spellingShingle | Zhonghai Du Xiuchen Han Liping Zhu Li Li Leandro Castellano Justin Stebbing Ling Peng Zhiqiang Wang An exosome mRNA-related gene risk model to evaluate the tumor microenvironment and predict prognosis in hepatocellular carcinoma BMC Medical Genomics Hepatocellular carcinoma Extracellular vesicle Exosome Risk score Prognostic signature Tumor immune microenvironment |
| title | An exosome mRNA-related gene risk model to evaluate the tumor microenvironment and predict prognosis in hepatocellular carcinoma |
| title_full | An exosome mRNA-related gene risk model to evaluate the tumor microenvironment and predict prognosis in hepatocellular carcinoma |
| title_fullStr | An exosome mRNA-related gene risk model to evaluate the tumor microenvironment and predict prognosis in hepatocellular carcinoma |
| title_full_unstemmed | An exosome mRNA-related gene risk model to evaluate the tumor microenvironment and predict prognosis in hepatocellular carcinoma |
| title_short | An exosome mRNA-related gene risk model to evaluate the tumor microenvironment and predict prognosis in hepatocellular carcinoma |
| title_sort | exosome mrna related gene risk model to evaluate the tumor microenvironment and predict prognosis in hepatocellular carcinoma |
| topic | Hepatocellular carcinoma Extracellular vesicle Exosome Risk score Prognostic signature Tumor immune microenvironment |
| url | https://doi.org/10.1186/s12920-024-01865-z |
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