Edward D Esplin, Casey Hanson, Si Wu, Aaron M Horning, Nasim Barapour, Stephanie A Nevins, Lihua Jiang, Kévin Contrepois, Hayan Lee, Tuhin K Guha, Zheng Hu, Rozelle Laquindanum, Meredith A Mills, Hassan Chaib, Roxanne Chiu, Ruiqi Jian, Joanne Chan, Mathew Ellenberger, Winston R Becker, Bahareh Bahmani, Aziz Khan, Basil Michael, Annika K Weimer, D Glen Esplin, Jeanne Shen, Samuel Lancaster, Emma Monte, Thomas V Karathanos, Uri Ladabaum, Teri A Longacre, Anshul Kundaje, Christina Curtis, William J Greenleaf, James M Ford, Michael P Snyder
{"title":"家族性腺瘤性息肉病的多组学分析揭示了与早期肿瘤发生相关的分子通路。","authors":"Edward D Esplin, Casey Hanson, Si Wu, Aaron M Horning, Nasim Barapour, Stephanie A Nevins, Lihua Jiang, Kévin Contrepois, Hayan Lee, Tuhin K Guha, Zheng Hu, Rozelle Laquindanum, Meredith A Mills, Hassan Chaib, Roxanne Chiu, Ruiqi Jian, Joanne Chan, Mathew Ellenberger, Winston R Becker, Bahareh Bahmani, Aziz Khan, Basil Michael, Annika K Weimer, D Glen Esplin, Jeanne Shen, Samuel Lancaster, Emma Monte, Thomas V Karathanos, Uri Ladabaum, Teri A Longacre, Anshul Kundaje, Christina Curtis, William J Greenleaf, James M Ford, Michael P Snyder","doi":"10.1038/s43018-024-00831-z","DOIUrl":null,"url":null,"abstract":"<p><p>Familial adenomatous polyposis (FAP) is a genetic disease causing hundreds of premalignant polyps in affected persons and is an ideal model to study transitions of early precancer states to colorectal cancer (CRC). We performed deep multiomic profiling of 93 samples, including normal mucosa, benign polyps and dysplastic polyps, from six persons with FAP. Transcriptomic, proteomic, metabolomic and lipidomic analyses revealed a dynamic choreography of thousands of molecular and cellular events that occur during precancerous transitions toward cancer formation. These involve processes such as cell proliferation, immune response, metabolic alterations (including amino acids and lipids), hormones and extracellular matrix proteins. Interestingly, activation of the arachidonic acid pathway was found to occur early in hyperplasia; this pathway is targeted by aspirin and other nonsteroidal anti-inflammatory drugs, a preventative treatment under investigation in persons with FAP. Overall, our results reveal key genomic, cellular and molecular events during the earliest steps in CRC formation and potential mechanisms of pharmaceutical prophylaxis.</p>","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":""},"PeriodicalIF":23.5000,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Multiomic analysis of familial adenomatous polyposis reveals molecular pathways associated with early tumorigenesis.\",\"authors\":\"Edward D Esplin, Casey Hanson, Si Wu, Aaron M Horning, Nasim Barapour, Stephanie A Nevins, Lihua Jiang, Kévin Contrepois, Hayan Lee, Tuhin K Guha, Zheng Hu, Rozelle Laquindanum, Meredith A Mills, Hassan Chaib, Roxanne Chiu, Ruiqi Jian, Joanne Chan, Mathew Ellenberger, Winston R Becker, Bahareh Bahmani, Aziz Khan, Basil Michael, Annika K Weimer, D Glen Esplin, Jeanne Shen, Samuel Lancaster, Emma Monte, Thomas V Karathanos, Uri Ladabaum, Teri A Longacre, Anshul Kundaje, Christina Curtis, William J Greenleaf, James M Ford, Michael P Snyder\",\"doi\":\"10.1038/s43018-024-00831-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Familial adenomatous polyposis (FAP) is a genetic disease causing hundreds of premalignant polyps in affected persons and is an ideal model to study transitions of early precancer states to colorectal cancer (CRC). We performed deep multiomic profiling of 93 samples, including normal mucosa, benign polyps and dysplastic polyps, from six persons with FAP. Transcriptomic, proteomic, metabolomic and lipidomic analyses revealed a dynamic choreography of thousands of molecular and cellular events that occur during precancerous transitions toward cancer formation. These involve processes such as cell proliferation, immune response, metabolic alterations (including amino acids and lipids), hormones and extracellular matrix proteins. Interestingly, activation of the arachidonic acid pathway was found to occur early in hyperplasia; this pathway is targeted by aspirin and other nonsteroidal anti-inflammatory drugs, a preventative treatment under investigation in persons with FAP. 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Multiomic analysis of familial adenomatous polyposis reveals molecular pathways associated with early tumorigenesis.
Familial adenomatous polyposis (FAP) is a genetic disease causing hundreds of premalignant polyps in affected persons and is an ideal model to study transitions of early precancer states to colorectal cancer (CRC). We performed deep multiomic profiling of 93 samples, including normal mucosa, benign polyps and dysplastic polyps, from six persons with FAP. Transcriptomic, proteomic, metabolomic and lipidomic analyses revealed a dynamic choreography of thousands of molecular and cellular events that occur during precancerous transitions toward cancer formation. These involve processes such as cell proliferation, immune response, metabolic alterations (including amino acids and lipids), hormones and extracellular matrix proteins. Interestingly, activation of the arachidonic acid pathway was found to occur early in hyperplasia; this pathway is targeted by aspirin and other nonsteroidal anti-inflammatory drugs, a preventative treatment under investigation in persons with FAP. Overall, our results reveal key genomic, cellular and molecular events during the earliest steps in CRC formation and potential mechanisms of pharmaceutical prophylaxis.
期刊介绍:
Cancer is a devastating disease responsible for millions of deaths worldwide. However, many of these deaths could be prevented with improved prevention and treatment strategies. To achieve this, it is crucial to focus on accurate diagnosis, effective treatment methods, and understanding the socioeconomic factors that influence cancer rates.
Nature Cancer aims to serve as a unique platform for sharing the latest advancements in cancer research across various scientific fields, encompassing life sciences, physical sciences, applied sciences, and social sciences. The journal is particularly interested in fundamental research that enhances our understanding of tumor development and progression, as well as research that translates this knowledge into clinical applications through innovative diagnostic and therapeutic approaches. Additionally, Nature Cancer welcomes clinical studies that inform cancer diagnosis, treatment, and prevention, along with contributions exploring the societal impact of cancer on a global scale.
In addition to publishing original research, Nature Cancer will feature Comments, Reviews, News & Views, Features, and Correspondence that hold significant value for the diverse field of cancer research.