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 |
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| المؤلفون: | Mark P. G. Dings, Paul Manoukian, Cynthia Waasdorp, Judith S. E. Quik, Marin Strijker, Sophie C. Lodestijn, Sanne M. van Neerven, Leandro F. Moreno, Rodrigo Leite de Oliveira, Bert A. Bonsing, Marco J. Bruno, Olivier R. Busch, Michael Doukas, Casper H. van Eijck, Nadia Haj Mohammad, Ignace H. de Hingh, Quintus I. Molenaar, Marc G. Besselink, Louis Vermeulen, Jan Paul Medema, Hanneke W. M. van Laarhoven, Maarten F. Bijlsma |
| المساهمون: | Pulmonary Medicine, Gastroenterology & Hepatology, Pathology, Surgery, Internal medicine, Center of Experimental and Molecular Medicine, Graduate School, CCA - Imaging and biomarkers, AII - Cancer immunology, CCA - Cancer biology and immunology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, CCA - Cancer Treatment and Quality of Life, Oncology |
| المصدر: | International Journal of Cancer, 152(3), 511-523. Wiley-Liss Inc. International Journal of Cancer, 152(3), 511-523. WILEY Dings, M P G, Manoukian, P, Waasdorp, C, Quik, J S E, Strijker, M, Lodestijn, S C, van Neerven, S M, Moreno, L F, de Oliveira, R L, Bonsing, B A, Bruno, M J, Busch, O R, Doukas, M, van Eijck, C H, Mohammad, N H, de Hingh, I H, Molenaar, Q I, Besselink, M G, Vermeulen, L, Medema, J P, van Laarhoven, H W M & Bijlsma, M F 2023, ' Serum levels of iCAF-derived osteoglycin predict favorable outcome in pancreatic cancer ', International Journal of Cancer, vol. 152, no. 3, pp. 511-523 . https://doi.org/10.1002/ijc.34276Test |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Cancer Research, CAF subtypes, pancreatic ductal adenocarcinoma, liquid biopsy center, Pancreatic Neoplasms, Mice, Oncology, Cancer-Associated Fibroblasts, Pancreatitis, SDG 3 - Good Health and Well-being, Tumor Microenvironment, stroma, Humans, Animals, Carcinoma, Pancreatic Ductal |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0020-7136 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fc3cf7b99880ba5044d3e85803aa329bTest https://pure.eur.nl/en/publications/4e1ed1ff-157e-4175-868e-0238266dcf34Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fc3cf7b99880ba5044d3e85803aa329b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00207136 |
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