دورية أكاديمية
CLDN18: Clinical, Pathological, and Genetic Signatures with Drug Screening in Gastric Adenocarcinoma.
| العنوان: | CLDN18: Clinical, Pathological, and Genetic Signatures with Drug Screening in Gastric Adenocarcinoma. |
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| المؤلفون: | Hur JY; Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Gyeonggi-do, Republic of Korea., Min KW; Department of Pathology, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu, Gyeonggi-do, Republic of Korea., Noh YK; Department of Computer Science, Hanyang University, Seoul, Republic of Korea.; School of Computational Sciences, Korea Institute for Advanced Study, Seoul, Republic of Korea., Won YW; Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Gyeonggi-do, Republic of Korea., Yeo Y; Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Gyeonggi-do, Republic of Korea., Kim DH; Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea., Son BK; Department of Internal Medicine, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu, Gyeonggi-do, Republic of Korea., Kwon MJ; Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Gyeonggi-do, Republic of Korea., Pyo JS; Department of Pathology, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu, Gyeonggi-do, Republic of Korea. |
| المصدر: | Current medicinal chemistry [Curr Med Chem] 2024 Apr 18. Date of Electronic Publication: 2024 Apr 18. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Bentham Science Publishers Country of Publication: United Arab Emirates NLM ID: 9440157 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1875-533X (Electronic) Linking ISSN: 09298673 NLM ISO Abbreviation: Curr Med Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Saif Zone, Sharjah, U.A.E. : Bentham Science Publishers Original Publication: Schiphol, The Netherlands : Bentham Science Publishers, |
| مستخلص: | Introduction: The CLDN18 gene, encoding claudin 18.1 and claudin 18.2, is a key component of tight junction strands in epithelial cells that form a paracellular barrier that is critical in Stomach Adenocarcinoma (STAD). Methods: Our study included 1,095 patients with proven STAD, 415 from The Cancer Genome Atlas (TCGA) cohort and 680 from the Gene Expression Omnibus database. We applied various analyses, including gene set enrichment analysis, pathway analysis, and in vitro drug screening to evaluate survival, immune cells, and genes and gene sets associated with cancer progression, based on CLDN18 expression levels. Gradient boosting machine learning (70% for training, 15% for validation, and 15% for testing) was used to evaluate the impact of CLDN18 on survival and develop a survival prediction model. Results: High CLDN18 expression correlated with worse survival in lymphocyte-poor STAD, accompanied by decreased helper T cells, altered metabolic genes, low necrosis-related gene expression, and increased tumor proliferation. CLDN18 expression showed associations with gene sets associated with various stomach, breast, ovarian, and esophageal cancers, while pathway analysis linked CLDN18 to immunity. Incorporating CLDN18 expression improved survival prediction in a machine learning model. Notably, nutlin-3a and niraparib effectively inhibited high CLDN18-expressing gastric cancer cells in drug screening. Conclusion: Our study provides a comprehensive understanding of the biological role of CLDN18-based bioinformatics and machine learning analysis in STAD, shedding light on its prognostic significance and potential therapeutic implications. To fully elucidate the molecular intricacies of CLDN18, further investigation is warranted, particularly through in vitro and in vivo studies. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.) |
| فهرسة مساهمة: | Keywords: CLDN18; drug; machine learning; niraparib; prognosis; stomach cancer |
| تواريخ الأحداث: | Date Created: 20240419 Latest Revision: 20240419 |
| رمز التحديث: | 20240419 |
| DOI: | 10.2174/0109298673288604240408065715 |
| PMID: | 38639279 |
| قاعدة البيانات: | MEDLINE |
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