Identification of molecular subtypes based on liquid–liquid phase separation and cross-talk with immunological phenotype in bladder cancer
BackgroundMounting evidence has demonstrated that an imbalance in liquid–liquid phase separation (LLPS) can induce alteration in the spatiotemporal coordination of biomolecular condensates, which plays a role in carcinogenesis and cachexia. However, the role of LLPS in the occurrence and progression...
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1059568/full |
| _version_ | 1828096740433068032 |
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| author | Le Sun Xiao-Ping Liu Xin Yan Shaojie Wu Xiaoyu Tang Chen Chen Gang Li Hankun Hu Du Wang Sheng Li Sheng Li |
| author_facet | Le Sun Xiao-Ping Liu Xin Yan Shaojie Wu Xiaoyu Tang Chen Chen Gang Li Hankun Hu Du Wang Sheng Li Sheng Li |
| author_sort | Le Sun |
| collection | DOAJ |
| description | BackgroundMounting evidence has demonstrated that an imbalance in liquid–liquid phase separation (LLPS) can induce alteration in the spatiotemporal coordination of biomolecular condensates, which plays a role in carcinogenesis and cachexia. However, the role of LLPS in the occurrence and progression of bladder cancer (BLCA) remains to be elucidated. Identifying the role of LLPS in carcinogenesis may aid in cancer therapeutics.MethodsA total of 1,351 BLCA samples from six cohorts were retrieved from publicly available databases like The Cancer Genome Atlas, Gene Expression Omnibus, and ArrayExpress. The samples were divided into three distinct clusters, and their multi-dimensional heterogeneities were explored. The LLPS patterns of all patients were determined based on the LLPS-related risk score (LLPSRS), and its multifaceted landscape was depicted and experimentally validated at the multi-omics level. Finally, a cytotoxicity-related and LLPSRS-based classifier was established to predict the patient’s response to immune checkpoint blockade (ICB) treatment.ResultsThree LLPS-related subtypes were identified and validated. The differences in prognosis, tumor microenvironment (TME) features, cancer hallmarks, and certain signatures of the three LLPS-related subtypes were validated. LLPSRS was calculated, which could be used as a prognostic biomarker. A close correlation was observed between clinicopathological features, genomic variations, biological mechanisms, immune infiltration in TME, chemosensitivity, and LLPSRS. Furthermore, our classifier could effectively predict immunotherapy response in patients with BLCA.ConclusionsOur study identified a novel categorization of BLCA patients based on LLPS. The LLPSRS could predict the prognosis of patients and aid in designing personalized medicine. Further, our binary classifier could effectively predict patients’ sensitivity to immunotherapy. |
| first_indexed | 2024-04-11T07:36:25Z |
| format | Article |
| id | doaj.art-64ce6ab741a44de992f6828df5a4b68c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T07:36:25Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-64ce6ab741a44de992f6828df5a4b68c2022-12-22T04:36:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-11-011310.3389/fimmu.2022.10595681059568Identification of molecular subtypes based on liquid–liquid phase separation and cross-talk with immunological phenotype in bladder cancerLe Sun0Xiao-Ping Liu1Xin Yan2Shaojie Wu3Xiaoyu Tang4Chen Chen5Gang Li6Hankun Hu7Du Wang8Sheng Li9Sheng Li10Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Biological Repositories, Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Biological Repositories, Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Biological Repositories, Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Pharmacy, Zhongnan Hospital of Wuhan University, Wuhan, ChinaThe Institute of Technological Sciences, Wuhan University, Wuhan, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Biological Repositories, Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan, ChinaBackgroundMounting evidence has demonstrated that an imbalance in liquid–liquid phase separation (LLPS) can induce alteration in the spatiotemporal coordination of biomolecular condensates, which plays a role in carcinogenesis and cachexia. However, the role of LLPS in the occurrence and progression of bladder cancer (BLCA) remains to be elucidated. Identifying the role of LLPS in carcinogenesis may aid in cancer therapeutics.MethodsA total of 1,351 BLCA samples from six cohorts were retrieved from publicly available databases like The Cancer Genome Atlas, Gene Expression Omnibus, and ArrayExpress. The samples were divided into three distinct clusters, and their multi-dimensional heterogeneities were explored. The LLPS patterns of all patients were determined based on the LLPS-related risk score (LLPSRS), and its multifaceted landscape was depicted and experimentally validated at the multi-omics level. Finally, a cytotoxicity-related and LLPSRS-based classifier was established to predict the patient’s response to immune checkpoint blockade (ICB) treatment.ResultsThree LLPS-related subtypes were identified and validated. The differences in prognosis, tumor microenvironment (TME) features, cancer hallmarks, and certain signatures of the three LLPS-related subtypes were validated. LLPSRS was calculated, which could be used as a prognostic biomarker. A close correlation was observed between clinicopathological features, genomic variations, biological mechanisms, immune infiltration in TME, chemosensitivity, and LLPSRS. Furthermore, our classifier could effectively predict immunotherapy response in patients with BLCA.ConclusionsOur study identified a novel categorization of BLCA patients based on LLPS. The LLPSRS could predict the prognosis of patients and aid in designing personalized medicine. Further, our binary classifier could effectively predict patients’ sensitivity to immunotherapy.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1059568/fullimmunotherapycytotoxicitybladder cancerliquid-liquid phase separationmolecular subtypesmachine learning |
| spellingShingle | Le Sun Xiao-Ping Liu Xin Yan Shaojie Wu Xiaoyu Tang Chen Chen Gang Li Hankun Hu Du Wang Sheng Li Sheng Li Identification of molecular subtypes based on liquid–liquid phase separation and cross-talk with immunological phenotype in bladder cancer Frontiers in Immunology immunotherapy cytotoxicity bladder cancer liquid-liquid phase separation molecular subtypes machine learning |
| title | Identification of molecular subtypes based on liquid–liquid phase separation and cross-talk with immunological phenotype in bladder cancer |
| title_full | Identification of molecular subtypes based on liquid–liquid phase separation and cross-talk with immunological phenotype in bladder cancer |
| title_fullStr | Identification of molecular subtypes based on liquid–liquid phase separation and cross-talk with immunological phenotype in bladder cancer |
| title_full_unstemmed | Identification of molecular subtypes based on liquid–liquid phase separation and cross-talk with immunological phenotype in bladder cancer |
| title_short | Identification of molecular subtypes based on liquid–liquid phase separation and cross-talk with immunological phenotype in bladder cancer |
| title_sort | identification of molecular subtypes based on liquid liquid phase separation and cross talk with immunological phenotype in bladder cancer |
| topic | immunotherapy cytotoxicity bladder cancer liquid-liquid phase separation molecular subtypes machine learning |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1059568/full |
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