MOICS, a novel classier deciphering immune heterogeneity and aid precise management of clear cell renal cell carcinoma at multiomics level
Recent studies have indicated that the tumor immune microenvironment plays a pivotal role in the initiation and progression of clear cell renal cell carcinoma (ccRCC). However, the characteristics and heterogeneity of tumor immunity in ccRCC, particularly at the multiomics level, remain poorly under...
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Taylor & Francis Group
2024-12-01
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| Series: | Cancer Biology & Therapy |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/15384047.2024.2345977 |
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| author | Ying Liu Lin Qi Bicheng Ye Anbang Wang Juan Lu Le Qu Peng Luo Linhui Wang Aimin Jiang |
| author_facet | Ying Liu Lin Qi Bicheng Ye Anbang Wang Juan Lu Le Qu Peng Luo Linhui Wang Aimin Jiang |
| author_sort | Ying Liu |
| collection | DOAJ |
| description | Recent studies have indicated that the tumor immune microenvironment plays a pivotal role in the initiation and progression of clear cell renal cell carcinoma (ccRCC). However, the characteristics and heterogeneity of tumor immunity in ccRCC, particularly at the multiomics level, remain poorly understood. We analyzed immune multiomics datasets to perform a consensus cluster analysis and validate the clustering results across multiple internal and external ccRCC datasets; and identified two distinctive immune phenotypes of ccRCC, which we named multiomics immune-based cancer subtype 1 (MOICS1) and subtype 2 (MOICS2). The former, MOICS1, is characterized by an immune-hot phenotype with poor clinical outcomes, marked by significant proliferation of CD4+ and CD8+ T cells, fibroblasts, and high levels of immune inhibitory signatures; the latter, MOICS2, exhibits an immune-cold phenotype with favorable clinical characteristics, characterized by robust immune activity and high infiltration of endothelial cells and immune stimulatory signatures. Besides, a significant negative correlation between immune infiltration and angiogenesis were identified. We further explored the mechanisms underlying these differences, revealing that negatively regulated endopeptidase activity, activated cornification, and neutrophil degranulation may promote an immune-deficient phenotype, whereas enhanced monocyte recruitment could ameliorate this deficiency. Additionally, significant differences were observed in the genomic landscapes between the subtypes: MOICS1 exhibited mutations in TTN, BAP1, SETD2, MTOR, MUC16, CSMD3, and AKAP9, while MOICS2 was characterized by notable alterations in the TGF-β pathway. Overall, our work demonstrates that multi-immune omics remodeling analysis enhances the understanding of the immune heterogeneity in ccRCC and supports precise patient management. |
| format | Article |
| id | doaj-art-02732bac3bc043d09c131f7ee750ee0a |
| institution | DOAJ |
| issn | 1538-4047 1555-8576 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Cancer Biology & Therapy |
| spelling | doaj-art-02732bac3bc043d09c131f7ee750ee0a2025-08-20T02:49:47ZengTaylor & Francis GroupCancer Biology & Therapy1538-40471555-85762024-12-0125110.1080/15384047.2024.2345977MOICS, a novel classier deciphering immune heterogeneity and aid precise management of clear cell renal cell carcinoma at multiomics levelYing Liu0Lin Qi1Bicheng Ye2Anbang Wang3Juan Lu4Le Qu5Peng Luo6Linhui Wang7Aimin Jiang8Department of Urology, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, ChinaDepartment of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaSchool of Clinical Medicine, Medical College of Yangzhou Polytechnic College, Yangzhou, ChinaDepartment of Urology, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, ChinaVocational Education Center, Naval Medical University (Second Military Medical University), Shanghai, ChinaDepartment of Urology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, ChinaDepartment of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Urology, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, ChinaDepartment of Urology, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, ChinaRecent studies have indicated that the tumor immune microenvironment plays a pivotal role in the initiation and progression of clear cell renal cell carcinoma (ccRCC). However, the characteristics and heterogeneity of tumor immunity in ccRCC, particularly at the multiomics level, remain poorly understood. We analyzed immune multiomics datasets to perform a consensus cluster analysis and validate the clustering results across multiple internal and external ccRCC datasets; and identified two distinctive immune phenotypes of ccRCC, which we named multiomics immune-based cancer subtype 1 (MOICS1) and subtype 2 (MOICS2). The former, MOICS1, is characterized by an immune-hot phenotype with poor clinical outcomes, marked by significant proliferation of CD4+ and CD8+ T cells, fibroblasts, and high levels of immune inhibitory signatures; the latter, MOICS2, exhibits an immune-cold phenotype with favorable clinical characteristics, characterized by robust immune activity and high infiltration of endothelial cells and immune stimulatory signatures. Besides, a significant negative correlation between immune infiltration and angiogenesis were identified. We further explored the mechanisms underlying these differences, revealing that negatively regulated endopeptidase activity, activated cornification, and neutrophil degranulation may promote an immune-deficient phenotype, whereas enhanced monocyte recruitment could ameliorate this deficiency. Additionally, significant differences were observed in the genomic landscapes between the subtypes: MOICS1 exhibited mutations in TTN, BAP1, SETD2, MTOR, MUC16, CSMD3, and AKAP9, while MOICS2 was characterized by notable alterations in the TGF-β pathway. Overall, our work demonstrates that multi-immune omics remodeling analysis enhances the understanding of the immune heterogeneity in ccRCC and supports precise patient management.https://www.tandfonline.com/doi/10.1080/15384047.2024.2345977Clear cell renal cell carcinomaimmune phenotypemultiomicsdrug sensitivityprognostic biomarker |
| spellingShingle | Ying Liu Lin Qi Bicheng Ye Anbang Wang Juan Lu Le Qu Peng Luo Linhui Wang Aimin Jiang MOICS, a novel classier deciphering immune heterogeneity and aid precise management of clear cell renal cell carcinoma at multiomics level Cancer Biology & Therapy Clear cell renal cell carcinoma immune phenotype multiomics drug sensitivity prognostic biomarker |
| title | MOICS, a novel classier deciphering immune heterogeneity and aid precise management of clear cell renal cell carcinoma at multiomics level |
| title_full | MOICS, a novel classier deciphering immune heterogeneity and aid precise management of clear cell renal cell carcinoma at multiomics level |
| title_fullStr | MOICS, a novel classier deciphering immune heterogeneity and aid precise management of clear cell renal cell carcinoma at multiomics level |
| title_full_unstemmed | MOICS, a novel classier deciphering immune heterogeneity and aid precise management of clear cell renal cell carcinoma at multiomics level |
| title_short | MOICS, a novel classier deciphering immune heterogeneity and aid precise management of clear cell renal cell carcinoma at multiomics level |
| title_sort | moics a novel classier deciphering immune heterogeneity and aid precise management of clear cell renal cell carcinoma at multiomics level |
| topic | Clear cell renal cell carcinoma immune phenotype multiomics drug sensitivity prognostic biomarker |
| url | https://www.tandfonline.com/doi/10.1080/15384047.2024.2345977 |
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