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Mechanistic insights into FEN1-mediated drug sensitivity and risk signature in colon cancer: An integrative bioinformatics study.

التفاصيل البيبلوغرافية
العنوان: Mechanistic insights into FEN1-mediated drug sensitivity and risk signature in colon cancer: An integrative bioinformatics study.
المؤلفون: Rao C; Department of Proctology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China., Tong J; Department of Proctology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China., Yang Y; Department of Otolaryngology, Banshan Community Health Service Center, Gongshu District, Hangzhou, Zhejiang, China.
المصدر: Medicine [Medicine (Baltimore)] 2024 Mar 29; Vol. 103 (13), pp. e37517.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 2985248R Publication Model: Print Cited Medium: Internet ISSN: 1536-5964 (Electronic) Linking ISSN: 00257974 NLM ISO Abbreviation: Medicine (Baltimore) Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Hagerstown, Md : Lippincott Williams & Wilkins
مواضيع طبية MeSH: Flap Endonucleases*/genetics , Flap Endonucleases*/metabolism , Colonic Neoplasms*/drug therapy , Colonic Neoplasms*/genetics , Colonic Neoplasms*/metabolism, Humans ; Prognosis ; Drug Resistance ; Computational Biology
مستخلص: The overexpression of Flap endonuclease 1 (FEN1) has been implicated in drug resistance and prognosis across various cancer types. However, the precise role of FEN1 in colon cancer remains to be fully elucidated. In this study, we employed comprehensive datasets from The Cancer Genome Atlas, Gene Expression Omnibus, and Human Protein Atlas to examine FEN1 expression and assess its correlation with clinical pathology and prognosis in colon cancer. We utilized the pRRophetic algorithm to evaluate drug sensitivity and performed differential expression analysis to identify genes associated with FEN1-mediated drug sensitivity. Gene set enrichment analysis was conducted to further investigate these genes. Additionally, single-cell sequencing analysis was employed to explore the relationship between FEN1 expression and functional states. Cox regression analysis was implemented to construct a prognostic model, and a nomogram for prognosis was developed. Our analysis of The Cancer Genome Atlas and Gene Expression Omnibus datasets revealed a significant upregulation of FEN1 in colon cancer. However, while FEN1 expression showed no notable correlation with prognosis, it displayed associations with metastasis. Single-cell sequencing analysis further confirmed a positive correlation between FEN1 expression and colon cancer metastasis. Furthermore, we detected marked discrepancies in drug responsiveness between the High_FEN1 and Low_FEN1 groups, identifying 342 differentially expressed genes. Enrichment analysis showed significant suppression in processes related to DNA replication, spliceosome, and cell cycle pathways in the Low_FEN1 group, while the calcium signaling pathway, cAMP signaling pathway, and other pathways were activated. Of the 197 genes differentially expressed and strongly linked to FEN1 expression, 39 were significantly implicated in colon cancer prognosis. Finally, we constructed a risk signature consisting of 5 genes, which, when combined with drug treatment and pathological staging, significantly improved the prediction of colon cancer prognosis. This study offers novel insights into the interplay among FEN1 expression levels, colon cancer metastatic potential, and sensitivity to therapeutic agents. Furthermore, we successfully developed a multi-gene prognostic risk signature derived from FEN1.
Competing Interests: The authors have no funding and conflicts of interest to disclose.
(Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)
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المشرفين على المادة: EC 3.1.- (Flap Endonucleases)
EC 3.1.11.- (FEN1 protein, human)
تواريخ الأحداث: Date Created: 20240329 Date Completed: 20240401 Latest Revision: 20240503
رمز التحديث: 20240504
مُعرف محوري في PubMed: PMC10977573
DOI: 10.1097/MD.0000000000037517
PMID: 38552056
قاعدة البيانات: MEDLINE
الوصف
تدمد:1536-5964
DOI:10.1097/MD.0000000000037517