دورية أكاديمية
Exploring the biology of ctDNA release in colorectal cancer.
العنوان: | Exploring the biology of ctDNA release in colorectal cancer. |
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المؤلفون: | Andersen L; Department of Molecular Medicine, Aarhus University Hospital, Denmark; Department of Clinical Medicine, Aarhus University, Denmark; Bioinformatics Research Centre, Aarhus University, Denmark., Kisistók J; Department of Molecular Medicine, Aarhus University Hospital, Denmark; Department of Clinical Medicine, Aarhus University, Denmark; Bioinformatics Research Centre, Aarhus University, Denmark., Henriksen TV; Department of Molecular Medicine, Aarhus University Hospital, Denmark; Department of Clinical Medicine, Aarhus University, Denmark., Bramsen JB; Department of Molecular Medicine, Aarhus University Hospital, Denmark; Department of Clinical Medicine, Aarhus University, Denmark., Reinert T; Department of Molecular Medicine, Aarhus University Hospital, Denmark; Department of Clinical Medicine, Aarhus University, Denmark., Øgaard N; Department of Molecular Medicine, Aarhus University Hospital, Denmark; Department of Clinical Medicine, Aarhus University, Denmark., Mattesen TB; Department of Molecular Medicine, Aarhus University Hospital, Denmark; Department of Clinical Medicine, Aarhus University, Denmark., Birkbak NJ; Department of Molecular Medicine, Aarhus University Hospital, Denmark; Department of Clinical Medicine, Aarhus University, Denmark; Bioinformatics Research Centre, Aarhus University, Denmark. Electronic address: nbirkbak@clin.au.dk., Andersen CL; Department of Molecular Medicine, Aarhus University Hospital, Denmark; Department of Clinical Medicine, Aarhus University, Denmark. Electronic address: cla@clin.au.dk. |
المصدر: | European journal of cancer (Oxford, England : 1990) [Eur J Cancer] 2024 Aug; Vol. 207, pp. 114186. Date of Electronic Publication: 2024 Jun 26. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Elsevier Science Ltd Country of Publication: England NLM ID: 9005373 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0852 (Electronic) Linking ISSN: 09598049 NLM ISO Abbreviation: Eur J Cancer Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Oxford : Elsevier Science Ltd Original Publication: Oxford ; New York : Pergamon Press, c1990- |
مواضيع طبية MeSH: | Colorectal Neoplasms*/genetics , Colorectal Neoplasms*/pathology , Colorectal Neoplasms*/blood , Circulating Tumor DNA*/genetics , Circulating Tumor DNA*/blood , Biomarkers, Tumor*/genetics , Biomarkers, Tumor*/blood, Humans ; Male ; Female ; Aged ; Middle Aged ; Microsatellite Instability ; Exome Sequencing ; Aged, 80 and over ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Lung Neoplasms/blood ; Adult |
مستخلص: | Background: Circulating tumor DNA (ctDNA) has emerged as a promising tool for early cancer detection and minimal residual disease monitoring. However, the biology underlying ctDNA release and its variation across cancer types and histologies remains poorly understood. This study investigated the biology behind ctDNA shedding in colorectal cancer. Methods: The study included a local cohort of 747 stage I-III colorectal cancer patients. All patients had ctDNA measurement prior to treatment and extensive clinical data. Primary tumor RNA sequencing and whole exome sequencing was performed in 95 and 652 patients respectively. Additionally, the study evaluated 89 non-small cell lung cancer patients from the TRACERx cohort, comprising primary tumor RNA sequencing and ctDNA measurement. Results: We found tumor size and proliferative capacity to be key factors associated with ctDNA shedding in colorectal cancer. Furthermore, we found that the secretory and CMS3 colorectal cancer subtypes exhibited lower ctDNA shedding, while microsatellite instability (MSI) tumors had higher levels of ctDNA. Mutational analysis did not reveal any genes or pathways associated with ctDNA shedding in colorectal cancer. A comparison of transcriptomic profiles across multiple cancer types demonstrated that colorectal cancer and lung squamous cell carcinoma tumors shared a high-proliferative ctDNA shedding phenotype, while lung adenocarcinoma tumors displayed a distinct low-proliferative subgroup. Additionally, proliferation levels correlated with ctDNA detection sensitivity across multiple cancer types. Conclusion: These findings suggest that tumor size and proliferative capacity are drivers of ctDNA release in colorectal cancer and provide insights into the biology of ctDNA shedding on a pan-cancer level. Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.) |
فهرسة مساهمة: | Keywords: Biomarkers tumor; Circulating tumor DNA; Colorectal neoplasms; Exome Sequencing; RNA-Seq |
المشرفين على المادة: | 0 (Circulating Tumor DNA) 0 (Biomarkers, Tumor) |
تواريخ الأحداث: | Date Created: 20240629 Date Completed: 20240712 Latest Revision: 20240712 |
رمز التحديث: | 20240713 |
DOI: | 10.1016/j.ejca.2024.114186 |
PMID: | 38943900 |
قاعدة البيانات: | MEDLINE |
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