دورية أكاديمية
Serum levels of iCAF-derived osteoglycin predict favorable outcome in pancreatic cancer.
| العنوان: | Serum levels of iCAF-derived osteoglycin predict favorable outcome in pancreatic cancer. |
|---|---|
| المؤلفون: | Dings MPG; Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.; Oncode Institute, Amsterdam, The Netherlands.; Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands., Manoukian P; Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.; Oncode Institute, Amsterdam, The Netherlands.; Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands., Waasdorp C; Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.; Oncode Institute, Amsterdam, The Netherlands.; Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands., Quik JSE; Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands., Strijker M; Department of Surgery, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands., Lodestijn SC; Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.; Oncode Institute, Amsterdam, The Netherlands.; Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands., van Neerven SM; Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.; Oncode Institute, Amsterdam, The Netherlands.; Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands., Moreno LF; Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.; Oncode Institute, Amsterdam, The Netherlands.; Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands., de Oliveira RL; Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.; Oncode Institute, Amsterdam, The Netherlands.; CRISPR Expertise Center, Cancer Center Amsterdam, Amsterdam University Medical Center, Amsterdam, The Netherlands., Bonsing BA; Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands., Bruno MJ; Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands., Busch OR; Department of Surgery, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands., Doukas M; Department of Pathology, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands., van Eijck CH; Department of Surgery, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands., Mohammad NH; Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., de Hingh IH; Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands., Molenaar QI; Department of Surgery, Regional Academic Cancer Center Utrecht, University Medical Center Utrecht and St Antonius Hospital, Nieuwegein, The Netherlands., Besselink MG; Department of Surgery, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands., Vermeulen L; Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.; Oncode Institute, Amsterdam, The Netherlands.; Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands., Medema JP; Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.; Oncode Institute, Amsterdam, The Netherlands.; Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands., van Laarhoven HWM; Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.; Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands.; Department of Medical Oncology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands., Bijlsma MF; Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.; Oncode Institute, Amsterdam, The Netherlands.; Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands. |
| المصدر: | International journal of cancer [Int J Cancer] 2023 Feb 01; Vol. 152 (3), pp. 511-523. Date of Electronic Publication: 2022 Sep 19. |
| نوع المنشور: | Meta-Analysis; Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Wiley-Liss Country of Publication: United States NLM ID: 0042124 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-0215 (Electronic) Linking ISSN: 00207136 NLM ISO Abbreviation: Int J Cancer Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 1995- : New York, NY : Wiley-Liss Original Publication: 1966-1984 : Genève : International Union Against Cancer |
| مواضيع طبية MeSH: | Pancreatic Neoplasms*/drug therapy , Pancreatic Neoplasms*/genetics , Pancreatic Neoplasms*/metabolism , Carcinoma, Pancreatic Ductal*/drug therapy , Carcinoma, Pancreatic Ductal*/genetics , Carcinoma, Pancreatic Ductal*/metabolism , Cancer-Associated Fibroblasts*/metabolism , Pancreatitis*/pathology, Humans ; Mice ; Animals ; Tumor Microenvironment ; Pancreatic Neoplasms |
| مستخلص: | Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma, the main cellular constituents of which are cancer-associated fibroblasts (CAFs). Stroma-targeting agents have been proposed to improve the poor outcome of current treatments. However, clinical trials using these agents showed disappointing results. Heterogeneity in the PDAC CAF population was recently delineated demonstrating that both tumor-promoting and tumor-suppressive activities co-exist in the stroma. Here, we aimed to identify biomarkers for the CAF population that contribute to a favorable outcome. RNA-sequencing reads from patient-derived xenografts (PDXs) were mapped to the human and mouse genome to allocate the expression of genes to the tumor or stroma. Survival meta-analysis for stromal genes was performed and applied to human protein atlas data to identify circulating biomarkers. The candidate protein was perturbed in co-cultures and assessed in existing and novel single-cell gene expression analysis from control, pancreatitis, pancreatitis-recovered and PDAC mouse models. Serum levels of the candidate biomarker were measured in two independent cohorts totaling 148 PDAC patients and related them to overall survival. Osteoglycin (OGN) was identified as a candidate serum prognostic marker. Single-cell analysis indicated that Ogn is derived from a subgroup of inflammatory CAFs. Ogn-expressing fibroblasts are distinct from resident healthy pancreatic stellate cells and arise during pancreatitis. Serum OGN levels were prognostic for favorable overall survival in two independent PDAC cohorts (HR = 0.47, P = .042 and HR = 0.53, P = .006). Altogether, we conclude that high circulating OGN levels inform on a previously unrecognized subgroup of CAFs and predict favorable outcomes in resectable PDAC. (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.) |
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| فهرسة مساهمة: | Keywords: CAF subtypes; liquid biopsy center; pancreatic ductal adenocarcinoma; stroma |
| تواريخ الأحداث: | Date Created: 20220907 Date Completed: 20221216 Latest Revision: 20231213 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC10087204 |
| DOI: | 10.1002/ijc.34276 |
| PMID: | 36069222 |
| قاعدة البيانات: | MEDLINE |
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