Single-cell analysis of a tumor-derived exosome signature correlates with prognosis and immunotherapy response
Abstract Background Tumor-derived exosomes (TEXs) are involved in tumor progression and the immune modulation process and mediate intercellular communication in the tumor microenvironment. Although exosomes are considered promising liquid biomarkers for disease diagnosis, it is difficult to discrimi...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-09-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-021-03053-4 |
| _version_ | 1829519192657756160 |
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| author | Jiani Wu Dongqiang Zeng Shimeng Zhi Zilan Ye Wenjun Qiu Na Huang Li Sun Chunlin Wang Zhenzhen Wu Jianping Bin Yulin Liao Min Shi Wangjun Liao |
| author_facet | Jiani Wu Dongqiang Zeng Shimeng Zhi Zilan Ye Wenjun Qiu Na Huang Li Sun Chunlin Wang Zhenzhen Wu Jianping Bin Yulin Liao Min Shi Wangjun Liao |
| author_sort | Jiani Wu |
| collection | DOAJ |
| description | Abstract Background Tumor-derived exosomes (TEXs) are involved in tumor progression and the immune modulation process and mediate intercellular communication in the tumor microenvironment. Although exosomes are considered promising liquid biomarkers for disease diagnosis, it is difficult to discriminate TEXs and to develop TEX-based predictive biomarkers. Methods In this study, the gene expression profiles and clinical information were collected from The Cancer Genome Atlas (TCGA) database, IMvigor210 cohorts, and six independent Gene Expression Omnibus datasets. A TEXs-associated signature named TEXscore was established to predict overall survival in multiple cancer types and in patients undergoing immune checkpoint blockade therapies. Results Based on exosome-associated genes, we first constructed a tumor-derived exosome signature named TEXscore using a principal component analysis algorithm. In single-cell RNA-sequencing data analysis, ascending TEXscore was associated with disease progression and poor clinical outcomes. In the TCGA Pan-Cancer cohort, TEXscore was elevated in tumor samples rather than in normal tissues, thereby serving as a reliable biomarker to distinguish cancer from non-cancer sources. Moreover, high TEXscore was associated with shorter overall survival across 12 cancer types. TEXscore showed great potential in predicting immunotherapy response in melanoma, urothelial cancer, and renal cancer. The immunosuppressive microenvironment characterized by macrophages, cancer-associated fibroblasts, and myeloid-derived suppressor cells was associated with high TEXscore in the TCGA and immunotherapy cohorts. Besides, TEXscore-associated miRNAs and gene mutations were also identified. Further experimental research will facilitate the extending of TEXscore in tumor-associated exosomes. Conclusions TEXscore capturing tumor-derived exosome features might be a robust biomarker for prognosis and treatment responses in independent cohorts. |
| first_indexed | 2024-12-16T14:34:55Z |
| format | Article |
| id | doaj.art-15d6c5f286ed4d439d715cfebd67bf44 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-16T14:34:55Z |
| publishDate | 2021-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-15d6c5f286ed4d439d715cfebd67bf442022-12-21T22:28:07ZengBMCJournal of Translational Medicine1479-58762021-09-0119111810.1186/s12967-021-03053-4Single-cell analysis of a tumor-derived exosome signature correlates with prognosis and immunotherapy responseJiani Wu0Dongqiang Zeng1Shimeng Zhi2Zilan Ye3Wenjun Qiu4Na Huang5Li Sun6Chunlin Wang7Zhenzhen Wu8Jianping Bin9Yulin Liao10Min Shi11Wangjun Liao12Department of Oncology, Nanfang Hospital, Southern Medical UniversityDepartment of Oncology, Nanfang Hospital, Southern Medical UniversityDepartment of Oncology, Nanfang Hospital, Southern Medical UniversityDepartment of Oncology, Nanfang Hospital, Southern Medical UniversityDepartment of Oncology, Nanfang Hospital, Southern Medical UniversityDepartment of Oncology, Nanfang Hospital, Southern Medical UniversityDepartment of Oncology, Nanfang Hospital, Southern Medical UniversityDepartment of Oncology, Nanfang Hospital, Southern Medical UniversityDepartment of Oncology, Nanfang Hospital, Southern Medical UniversityDepartment of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical UniversityDepartment of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical UniversityDepartment of Oncology, Nanfang Hospital, Southern Medical UniversityDepartment of Oncology, Nanfang Hospital, Southern Medical UniversityAbstract Background Tumor-derived exosomes (TEXs) are involved in tumor progression and the immune modulation process and mediate intercellular communication in the tumor microenvironment. Although exosomes are considered promising liquid biomarkers for disease diagnosis, it is difficult to discriminate TEXs and to develop TEX-based predictive biomarkers. Methods In this study, the gene expression profiles and clinical information were collected from The Cancer Genome Atlas (TCGA) database, IMvigor210 cohorts, and six independent Gene Expression Omnibus datasets. A TEXs-associated signature named TEXscore was established to predict overall survival in multiple cancer types and in patients undergoing immune checkpoint blockade therapies. Results Based on exosome-associated genes, we first constructed a tumor-derived exosome signature named TEXscore using a principal component analysis algorithm. In single-cell RNA-sequencing data analysis, ascending TEXscore was associated with disease progression and poor clinical outcomes. In the TCGA Pan-Cancer cohort, TEXscore was elevated in tumor samples rather than in normal tissues, thereby serving as a reliable biomarker to distinguish cancer from non-cancer sources. Moreover, high TEXscore was associated with shorter overall survival across 12 cancer types. TEXscore showed great potential in predicting immunotherapy response in melanoma, urothelial cancer, and renal cancer. The immunosuppressive microenvironment characterized by macrophages, cancer-associated fibroblasts, and myeloid-derived suppressor cells was associated with high TEXscore in the TCGA and immunotherapy cohorts. Besides, TEXscore-associated miRNAs and gene mutations were also identified. Further experimental research will facilitate the extending of TEXscore in tumor-associated exosomes. Conclusions TEXscore capturing tumor-derived exosome features might be a robust biomarker for prognosis and treatment responses in independent cohorts.https://doi.org/10.1186/s12967-021-03053-4Tumor-derived exosomeSingle-cell analysisBiomarkerImmunotherapyTumor microenvironment |
| spellingShingle | Jiani Wu Dongqiang Zeng Shimeng Zhi Zilan Ye Wenjun Qiu Na Huang Li Sun Chunlin Wang Zhenzhen Wu Jianping Bin Yulin Liao Min Shi Wangjun Liao Single-cell analysis of a tumor-derived exosome signature correlates with prognosis and immunotherapy response Journal of Translational Medicine Tumor-derived exosome Single-cell analysis Biomarker Immunotherapy Tumor microenvironment |
| title | Single-cell analysis of a tumor-derived exosome signature correlates with prognosis and immunotherapy response |
| title_full | Single-cell analysis of a tumor-derived exosome signature correlates with prognosis and immunotherapy response |
| title_fullStr | Single-cell analysis of a tumor-derived exosome signature correlates with prognosis and immunotherapy response |
| title_full_unstemmed | Single-cell analysis of a tumor-derived exosome signature correlates with prognosis and immunotherapy response |
| title_short | Single-cell analysis of a tumor-derived exosome signature correlates with prognosis and immunotherapy response |
| title_sort | single cell analysis of a tumor derived exosome signature correlates with prognosis and immunotherapy response |
| topic | Tumor-derived exosome Single-cell analysis Biomarker Immunotherapy Tumor microenvironment |
| url | https://doi.org/10.1186/s12967-021-03053-4 |
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