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Mapping the intricacies of GLI1 in hedgehog signaling: A combined bioinformatics and clinical analysis in Head & Neck cancer in Western India.

التفاصيل البيبلوغرافية
العنوان: Mapping the intricacies of GLI1 in hedgehog signaling: A combined bioinformatics and clinical analysis in Head & Neck cancer in Western India.
المؤلفون: Patel HV; Junior Research Fellow, Molecular Diagnostic and Research Lab-3, Department of Cancer Biology, The Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India., Shah FD; Junior Research Fellow, Molecular Diagnostic and Research Lab-3, Department of Cancer Biology, The Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India. Electronic address: franky.shah@gcriindia.org.
المصدر: Current problems in cancer [Curr Probl Cancer] 2024 Sep 11; Vol. 53, pp. 101146. Date of Electronic Publication: 2024 Sep 11.
Publication Model: Ahead of Print
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Mosby Country of Publication: United States NLM ID: 7702986 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1535-6345 (Electronic) Linking ISSN: 01470272 NLM ISO Abbreviation: Curr Probl Cancer Subsets: MEDLINE
أسماء مطبوعة: Publication: St. Louis : Mosby
Original Publication: Chicago, Year Book Medical Publishers.
مستخلص: Background: Activation of various cancer stem cell pathways are thought to be responsible for treatment failure and loco-regional recurrence in Head and Neck cancer. Hedgehog signaling, a major cancer stem signaling pathway plays a major role in relapse of disease. GLI1, a transcription activator, plays an important role in canonical/non-canonical activation of Hedgehog signaling.
Methods: Data for H&N cancer patients were collected from The Cancer Genome Atlas- H&N Cancer (TCGA-HNSC). GLI1 co-expressed genes in TCGA-HNSC were then identified using cBioPortal and subjected to KEGG pathway analysis by DAVID tool. Network Analyzer and GeneMania plugins from CytoScape were used to identify hub genes and predict a probable pathway from the identified hub genes respectively. To confirm the hypothesis, real-time gene expression was carried out in 75 patients of head and neck cancer.
Results: Significantly higher GLI1 expression was observed in tumor tissues of H&N cancer and it also showed worst overall survival. Using cBioPortal tool, 2345 genes were identified that were significantly co-expressed with GLI1. From which, 15 hub genes were identified through the Network Analyzer plugin in CytoScape. A probable pathway prediction based on hub genes showed the interconnected molecular mechanism and its role in non-canonical activation of Hedgehog pathway by altering the GLI1 activity. The expressions of SHH, GLI1 and AKT1 were significant with each other and were found to be significantly associated with Age, Lymph-Node status and Keratin.
Conclusion: The study emphasizes the critical role of the Hh pathway's activation modes in H&N cancer, particularly highlighting the non-canonical activation through GLI1 and AKT1. The identification of SHH, GLI1 and AKT1 as potential diagnostic biomarkers and their association with clinic-pathological parameters underscores their relevance in prognostication and treatment planning. Hh pathway activation through GLI1 and its cross-talk with various pathways opens up the possibility of newer treatment strategies and developing a panel of therapeutic targets in H&N cancer patients.
Competing Interests: Declaration of competing interest The authors have no conflict of interest in the paper and has been not previously published in any of the journal.
(Copyright © 2024. Published by Elsevier Inc.)
فهرسة مساهمة: Keywords: Cancer signaling pathway; Cancer stem-like cells; GLI1; H&N Cancer; Hedgehog signaling; Non-canonical activation
تواريخ الأحداث: Date Created: 20240912 Latest Revision: 20240912
رمز التحديث: 20240913
DOI: 10.1016/j.currproblcancer.2024.101146
PMID: 39265246
قاعدة البيانات: MEDLINE
الوصف
تدمد:1535-6345
DOI:10.1016/j.currproblcancer.2024.101146