Integrative Transcriptomic Analysis Reveals Distinctive Molecular Traits and Novel Subtypes of Collecting Duct Carcinoma
Collecting duct carcinoma (CDC) is a rare and highly aggressive kidney cancer subtype with poor prognosis and no standard treatments. To date, only a few studies have examined the transcriptomic portrait of CDC. Through integration of multiple datasets, we compared CDC to normal tissue, upper-tract...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/12/2903 |
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| author | Chiara Gargiuli Pierangela Sepe Anna Tessari Tyler Sheetz Maurizio Colecchia Filippo Guglielmo Maria de Braud Giuseppe Procopio Marialuisa Sensi Elena Verzoni Matteo Dugo |
| author_facet | Chiara Gargiuli Pierangela Sepe Anna Tessari Tyler Sheetz Maurizio Colecchia Filippo Guglielmo Maria de Braud Giuseppe Procopio Marialuisa Sensi Elena Verzoni Matteo Dugo |
| author_sort | Chiara Gargiuli |
| collection | DOAJ |
| description | Collecting duct carcinoma (CDC) is a rare and highly aggressive kidney cancer subtype with poor prognosis and no standard treatments. To date, only a few studies have examined the transcriptomic portrait of CDC. Through integration of multiple datasets, we compared CDC to normal tissue, upper-tract urothelial carcinomas, and other renal cancers, including clear cell, papillary, and chromophobe histologies. Association between CDC gene expression signatures and in vitro drug sensitivity data was evaluated using the Cancer Therapeutic Response Portal, Genomics of Drug Sensitivity in Cancer datasets, and connectivity map. We identified a CDC-specific gene signature that predicted in vitro sensitivity to different targeted agents and was associated to worse outcome in clear cell renal cell carcinoma. We showed that CDC are transcriptionally related to the principal cells of the collecting ducts providing evidence that this tumor originates from this normal kidney cell type. Finally, we proved that CDC is a molecularly heterogeneous disease composed of at least two subtypes distinguished by cell signaling, metabolic and immune-related alterations. Our findings elucidate the molecular features of CDC providing novel biological and clinical insights. The identification of distinct CDC subtypes and their transcriptomic traits provides the rationale for patient stratification and alternative therapeutic approaches. |
| first_indexed | 2024-03-10T10:32:35Z |
| format | Article |
| id | doaj.art-c64e1ee13d95440da14d2cb7244a008e |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T10:32:35Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-c64e1ee13d95440da14d2cb7244a008e2023-11-21T23:35:23ZengMDPI AGCancers2072-66942021-06-011312290310.3390/cancers13122903Integrative Transcriptomic Analysis Reveals Distinctive Molecular Traits and Novel Subtypes of Collecting Duct CarcinomaChiara Gargiuli0Pierangela Sepe1Anna Tessari2Tyler Sheetz3Maurizio Colecchia4Filippo Guglielmo Maria de Braud5Giuseppe Procopio6Marialuisa Sensi7Elena Verzoni8Matteo Dugo9Platform of Integrated Biology, Department of Applied Research and Technology Development, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, ItalyDepartment of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, ItalyDepartment of Cancer Biology and Genetics, College of Medicine and Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USADepartment of Cancer Biology and Genetics, College of Medicine and Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USADepartment of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, ItalyDepartment of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, ItalyDepartment of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, ItalyPlatform of Integrated Biology, Department of Applied Research and Technology Development, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, ItalyDepartment of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, ItalyPlatform of Integrated Biology, Department of Applied Research and Technology Development, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, ItalyCollecting duct carcinoma (CDC) is a rare and highly aggressive kidney cancer subtype with poor prognosis and no standard treatments. To date, only a few studies have examined the transcriptomic portrait of CDC. Through integration of multiple datasets, we compared CDC to normal tissue, upper-tract urothelial carcinomas, and other renal cancers, including clear cell, papillary, and chromophobe histologies. Association between CDC gene expression signatures and in vitro drug sensitivity data was evaluated using the Cancer Therapeutic Response Portal, Genomics of Drug Sensitivity in Cancer datasets, and connectivity map. We identified a CDC-specific gene signature that predicted in vitro sensitivity to different targeted agents and was associated to worse outcome in clear cell renal cell carcinoma. We showed that CDC are transcriptionally related to the principal cells of the collecting ducts providing evidence that this tumor originates from this normal kidney cell type. Finally, we proved that CDC is a molecularly heterogeneous disease composed of at least two subtypes distinguished by cell signaling, metabolic and immune-related alterations. Our findings elucidate the molecular features of CDC providing novel biological and clinical insights. The identification of distinct CDC subtypes and their transcriptomic traits provides the rationale for patient stratification and alternative therapeutic approaches.https://www.mdpi.com/2072-6694/13/12/2903kidney cancerrenal cell carcinomascollecting duct carcinomatranscriptomicmolecular subtypesgene expression |
| spellingShingle | Chiara Gargiuli Pierangela Sepe Anna Tessari Tyler Sheetz Maurizio Colecchia Filippo Guglielmo Maria de Braud Giuseppe Procopio Marialuisa Sensi Elena Verzoni Matteo Dugo Integrative Transcriptomic Analysis Reveals Distinctive Molecular Traits and Novel Subtypes of Collecting Duct Carcinoma Cancers kidney cancer renal cell carcinomas collecting duct carcinoma transcriptomic molecular subtypes gene expression |
| title | Integrative Transcriptomic Analysis Reveals Distinctive Molecular Traits and Novel Subtypes of Collecting Duct Carcinoma |
| title_full | Integrative Transcriptomic Analysis Reveals Distinctive Molecular Traits and Novel Subtypes of Collecting Duct Carcinoma |
| title_fullStr | Integrative Transcriptomic Analysis Reveals Distinctive Molecular Traits and Novel Subtypes of Collecting Duct Carcinoma |
| title_full_unstemmed | Integrative Transcriptomic Analysis Reveals Distinctive Molecular Traits and Novel Subtypes of Collecting Duct Carcinoma |
| title_short | Integrative Transcriptomic Analysis Reveals Distinctive Molecular Traits and Novel Subtypes of Collecting Duct Carcinoma |
| title_sort | integrative transcriptomic analysis reveals distinctive molecular traits and novel subtypes of collecting duct carcinoma |
| topic | kidney cancer renal cell carcinomas collecting duct carcinoma transcriptomic molecular subtypes gene expression |
| url | https://www.mdpi.com/2072-6694/13/12/2903 |
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