Chenyue Lu, Amaya Pankaj, Michael Raabe, Cole Nawrocki, Ann Liu, Nova Xu, Bidish K Patel, Matthew J Emmett, Avril K Coley, Cristina R Ferrone, Vikram Deshpande, Irun Bhan, Yujin Hoshida, David T Ting, Martin J Aryee, Joseph W Franses
{"title":"HCC 空间转录组剖析揭示了癌症与内皮之间重要的、潜在的靶向相互作用。","authors":"Chenyue Lu, Amaya Pankaj, Michael Raabe, Cole Nawrocki, Ann Liu, Nova Xu, Bidish K Patel, Matthew J Emmett, Avril K Coley, Cristina R Ferrone, Vikram Deshpande, Irun Bhan, Yujin Hoshida, David T Ting, Martin J Aryee, Joseph W Franses","doi":"10.1097/HC9.0000000000000533","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>HCC is a highly vascular tumor, and many effective drug regimens target the tumor blood vessels. Prior bulk HCC subtyping data used bulk transcriptomes, which contained a mixture of parenchymal and stromal contributions.</p><p><strong>Methods: </strong>We utilized computational deconvolution and cell-cell interaction analyses to cell type-specific (tumor-enriched and vessel-enriched) spatial transcriptomic data collected from 41 resected HCC tissue specimens.</p><p><strong>Results: </strong>We report that the prior Hoshida bulk transcriptional subtyping schema is driven largely by an endothelial fraction, show an alternative tumor-specific schema has potential prognostic value, and use spatially paired ligand-receptor analyses to identify known and novel (LGALS9 tumor-HAVCR2 vessel) signaling relationships that drive HCC biology in a subtype-specific and potentially targetable manner.</p><p><strong>Conclusions: </strong>Our study leverages spatial gene expression profiling technologies to dissect HCC heterogeneity and identify heterogeneous signaling relationships between cancer cells and their endothelial cells. Future validation and expansion of these findings may validate novel cancer-endothelial cell interactions and related drug targets.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"8 10","pages":""},"PeriodicalIF":5.6000,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11441860/pdf/","citationCount":"0","resultStr":"{\"title\":\"HCC spatial transcriptomic profiling reveals significant and potentially targetable cancer-endothelial interactions.\",\"authors\":\"Chenyue Lu, Amaya Pankaj, Michael Raabe, Cole Nawrocki, Ann Liu, Nova Xu, Bidish K Patel, Matthew J Emmett, Avril K Coley, Cristina R Ferrone, Vikram Deshpande, Irun Bhan, Yujin Hoshida, David T Ting, Martin J Aryee, Joseph W Franses\",\"doi\":\"10.1097/HC9.0000000000000533\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>HCC is a highly vascular tumor, and many effective drug regimens target the tumor blood vessels. Prior bulk HCC subtyping data used bulk transcriptomes, which contained a mixture of parenchymal and stromal contributions.</p><p><strong>Methods: </strong>We utilized computational deconvolution and cell-cell interaction analyses to cell type-specific (tumor-enriched and vessel-enriched) spatial transcriptomic data collected from 41 resected HCC tissue specimens.</p><p><strong>Results: </strong>We report that the prior Hoshida bulk transcriptional subtyping schema is driven largely by an endothelial fraction, show an alternative tumor-specific schema has potential prognostic value, and use spatially paired ligand-receptor analyses to identify known and novel (LGALS9 tumor-HAVCR2 vessel) signaling relationships that drive HCC biology in a subtype-specific and potentially targetable manner.</p><p><strong>Conclusions: </strong>Our study leverages spatial gene expression profiling technologies to dissect HCC heterogeneity and identify heterogeneous signaling relationships between cancer cells and their endothelial cells. Future validation and expansion of these findings may validate novel cancer-endothelial cell interactions and related drug targets.</p>\",\"PeriodicalId\":12978,\"journal\":{\"name\":\"Hepatology Communications\",\"volume\":\"8 10\",\"pages\":\"\"},\"PeriodicalIF\":5.6000,\"publicationDate\":\"2024-09-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11441860/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Hepatology Communications\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/HC9.0000000000000533\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/10/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hepatology Communications","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/HC9.0000000000000533","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
Background: HCC is a highly vascular tumor, and many effective drug regimens target the tumor blood vessels. Prior bulk HCC subtyping data used bulk transcriptomes, which contained a mixture of parenchymal and stromal contributions.
Methods: We utilized computational deconvolution and cell-cell interaction analyses to cell type-specific (tumor-enriched and vessel-enriched) spatial transcriptomic data collected from 41 resected HCC tissue specimens.
Results: We report that the prior Hoshida bulk transcriptional subtyping schema is driven largely by an endothelial fraction, show an alternative tumor-specific schema has potential prognostic value, and use spatially paired ligand-receptor analyses to identify known and novel (LGALS9 tumor-HAVCR2 vessel) signaling relationships that drive HCC biology in a subtype-specific and potentially targetable manner.
Conclusions: Our study leverages spatial gene expression profiling technologies to dissect HCC heterogeneity and identify heterogeneous signaling relationships between cancer cells and their endothelial cells. Future validation and expansion of these findings may validate novel cancer-endothelial cell interactions and related drug targets.
期刊介绍:
Hepatology Communications is a peer-reviewed, online-only, open access journal for fast dissemination of high quality basic, translational, and clinical research in hepatology. Hepatology Communications maintains high standard and rigorous peer review. Because of its open access nature, authors retain the copyright to their works, all articles are immediately available and free to read and share, and it is fully compliant with funder and institutional mandates. The journal is committed to fast publication and author satisfaction.