دورية أكاديمية
Clinical Implications and Molecular Features of Extracellular Matrix Networks in Soft Tissue Sarcomas.
| العنوان: | Clinical Implications and Molecular Features of Extracellular Matrix Networks in Soft Tissue Sarcomas. |
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| المؤلفون: | Pankova V; Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom., Krasny L; Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom., Kerrison W; Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom., Tam YB; Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom., Chadha M; Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom., Burns J; Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom., Wilding CP; Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom., Chen L; Precision Sarcoma Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.; National Center for Tumor Diseases, Heidelberg, Germany., Chowdhury A; Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom., Perkins E; Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom., Lee ATJ; The Christie NHS Foundation Trust, Manchester, United Kingdom., Howell L; Light Microscopy Facility, The Institute of Cancer Research, London, United Kingdom., Guljar N; Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom., Sisley K; Division of Clinical Medicine, The Medical School, University of Sheffield, Sheffield, United Kingdom., Fisher C; University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom., Chudasama P; Precision Sarcoma Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.; National Center for Tumor Diseases, Heidelberg, Germany., Thway K; Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom.; The Royal Marsden NHS Foundation Trust, London, United Kingdom., Jones RL; The Royal Marsden NHS Foundation Trust, London, United Kingdom.; Division of Clinical Studies, The Institute of Cancer Research, London, United Kingdom., Huang PH; Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom. |
| المصدر: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2024 Aug 01; Vol. 30 (15), pp. 3229-3242. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: The Association Country of Publication: United States NLM ID: 9502500 Publication Model: Print Cited Medium: Internet ISSN: 1557-3265 (Electronic) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Denville, NJ : The Association, c1995- |
| مواضيع طبية MeSH: | Extracellular Matrix*/metabolism , Sarcoma*/pathology , Sarcoma*/genetics , Sarcoma*/metabolism , Proteomics*/methods, Humans ; Prognosis ; Female ; Male ; Signal Transduction ; Biomarkers, Tumor/metabolism ; Middle Aged ; Aged |
| مستخلص: | Purpose: The landscape of extracellular matrix (ECM) alterations in soft tissue sarcomas (STS) remains poorly characterized. We aimed to investigate the tumor ECM and adhesion signaling networks present in STS and their clinical implications. Experimental Design: Proteomic and clinical data from 321 patients across 11 histological subtypes were analyzed to define ECM and integrin adhesion networks. Subgroup analysis was performed in leiomyosarcomas (LMS), dedifferentiated liposarcomas (DDLPS), and undifferentiated pleomorphic sarcomas (UPS). Results: This analysis defined subtype-specific ECM profiles including enrichment of basement membrane proteins in LMS and ECM proteases in UPS. Across the cohort, we identified three distinct coregulated ECM networks which are associated with tumor malignancy grade and histological subtype. Comparative analysis of LMS cell line and patient proteomic data identified the lymphocyte cytosolic protein 1 cytoskeletal protein as a prognostic factor in LMS. Characterization of ECM network events in DDLPS revealed three subtypes with distinct oncogenic signaling pathways and survival outcomes. Evaluation of the DDLPS subtype with the poorest prognosis nominates ECM remodeling proteins as candidate antistromal therapeutic targets. Finally, we define a proteoglycan signature that is an independent prognostic factor for overall survival in DDLPS and UPS. Conclusions: STS comprise heterogeneous ECM signaling networks and matrix-specific features that have utility for risk stratification and therapy selection, which could in future guide precision medicine in these rare cancers. (©2024 The Authors; Published by the American Association for Cancer Research.) |
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| معلومات مُعتمدة: | SUK02.2018 Sarcoma UK (SUK); C56167/A29363 Cancer Research UK (CRUK); NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research (BRC); Royal Marsden Cancer Charity (The Royal Marsden Cancer Charity); Institute of Cancer Research (ICR); CH-2302 German Research Foundation; 01KD2207A German Federal Ministry of Education; 849906 Sarcoma Foundation of America (SFA) |
| المشرفين على المادة: | 0 (Biomarkers, Tumor) |
| تواريخ الأحداث: | Date Created: 20240529 Date Completed: 20240801 Latest Revision: 20240803 |
| رمز التحديث: | 20240803 |
| مُعرف محوري في PubMed: | PMC11292195 |
| DOI: | 10.1158/1078-0432.CCR-23-3960 |
| PMID: | 38810090 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1557-3265 |
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| DOI: | 10.1158/1078-0432.CCR-23-3960 |