Soluble stroma‐related biomarkers of pancreatic cancer
Abstract The clinical management of pancreatic ductal adenocarcinoma (PDAC) is hampered by the lack of reliable biomarkers. This study investigated the value of soluble stroma‐related molecules as PDAC biomarkers. In the first exploratory phase, 12 out of 38 molecules were associated with PDAC in a...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2018-08-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.201708741 |
| _version_ | 1797287736481153024 |
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| author | Andrea Resovi Maria Rosa Bani Luca Porcu Alessia Anastasia Lucia Minoli Paola Allavena Paola Cappello Francesco Novelli Aldo Scarpa Eugenio Morandi Anna Falanga Valter Torri Giulia Taraboletti Dorina Belotti Raffaella Giavazzi |
| author_facet | Andrea Resovi Maria Rosa Bani Luca Porcu Alessia Anastasia Lucia Minoli Paola Allavena Paola Cappello Francesco Novelli Aldo Scarpa Eugenio Morandi Anna Falanga Valter Torri Giulia Taraboletti Dorina Belotti Raffaella Giavazzi |
| author_sort | Andrea Resovi |
| collection | DOAJ |
| description | Abstract The clinical management of pancreatic ductal adenocarcinoma (PDAC) is hampered by the lack of reliable biomarkers. This study investigated the value of soluble stroma‐related molecules as PDAC biomarkers. In the first exploratory phase, 12 out of 38 molecules were associated with PDAC in a cohort of 25 PDAC patients and 16 healthy subjects. A second confirmatory phase on an independent cohort of 131 PDAC patients, 30 chronic pancreatitis patients, and 131 healthy subjects confirmed the PDAC association for MMP7, CCN2, IGFBP2, TSP2, sICAM1, TIMP1, and PLG. Multivariable logistic regression model identified biomarker panels discriminating respectively PDAC versus healthy subjects (MMP7 + CA19.9, AUC = 0.99, 99% CI = 0.98–1.00) (CCN2 + CA19.9, AUC = 0.96, 99% CI = 0.92–0.99) and PDAC versus chronic pancreatitis (CCN2 + PLG+FN+Col4 + CA19.9, AUC = 0.94, 99% CI = 0.88–0.99). Five molecules were associated with PanIN development in two GEM models of PDAC (PdxCre/LSL‐KrasG12D and PdxCre/LSL‐KrasG12D/+/LSL‐Trp53R172H/+), suggesting their potential for detecting early disease. These markers were also elevated in patient‐derived orthotopic PDAC xenografts and associated with response to chemotherapy. The identified stroma‐related soluble biomarkers represent potential tools for PDAC diagnosis and for monitoring treatment response of PDAC patients. |
| first_indexed | 2024-03-07T18:38:47Z |
| format | Article |
| id | doaj.art-e47a6b26a16a45e391d78f0c384f31c5 |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2024-03-07T18:38:47Z |
| publishDate | 2018-08-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-e47a6b26a16a45e391d78f0c384f31c52024-03-02T04:43:28ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842018-08-01108n/an/a10.15252/emmm.201708741Soluble stroma‐related biomarkers of pancreatic cancerAndrea Resovi0Maria Rosa Bani1Luca Porcu2Alessia Anastasia3Lucia Minoli4Paola Allavena5Paola Cappello6Francesco Novelli7Aldo Scarpa8Eugenio Morandi9Anna Falanga10Valter Torri11Giulia Taraboletti12Dorina Belotti13Raffaella Giavazzi14Laboratory of Biology and Treatment of Metastasis Department of Oncology IRCCS‐Istituto di Ricerche Farmacologiche Mario Negri Bergamo and Milan ItalyLaboratory of Biology and Treatment of Metastasis Department of Oncology IRCCS‐Istituto di Ricerche Farmacologiche Mario Negri Bergamo and Milan ItalyLaboratory of Methodology for Clinical Research Department of Oncology IRCCS‐Istituto di Ricerche Farmacologiche Mario Negri Milan ItalyLaboratory of Biology and Treatment of Metastasis Department of Oncology IRCCS‐Istituto di Ricerche Farmacologiche Mario Negri Bergamo and Milan ItalyMouse and Animal Pathology Lab, Fondazione Filarete and Department of Veterinary Pathology University of Milan Milan ItalyDepartment of Immunology and Inflammation IRCCS‐Humanitas Clinical and Research Center Rozzano ItalyCERMS, AOU Città della Salute e della Scienza Turin ItalyCERMS, AOU Città della Salute e della Scienza Turin ItalyDepartment of Pathology and Diagnostic University and Hospital Trust of Verona Verona ItalyChirurgia IV, Presidio Ospedaliero di Rho, ASST Rhodense Milano ItalyDepartment of Immunohematology and Transfusion Medicine Thrombosis and Hemostasis Center Hospital Papa Giovanni XXIII Bergamo ItalyLaboratory of Methodology for Clinical Research Department of Oncology IRCCS‐Istituto di Ricerche Farmacologiche Mario Negri Milan ItalyLaboratory of Biology and Treatment of Metastasis Department of Oncology IRCCS‐Istituto di Ricerche Farmacologiche Mario Negri Bergamo and Milan ItalyLaboratory of Biology and Treatment of Metastasis Department of Oncology IRCCS‐Istituto di Ricerche Farmacologiche Mario Negri Bergamo and Milan ItalyLaboratory of Biology and Treatment of Metastasis Department of Oncology IRCCS‐Istituto di Ricerche Farmacologiche Mario Negri Bergamo and Milan ItalyAbstract The clinical management of pancreatic ductal adenocarcinoma (PDAC) is hampered by the lack of reliable biomarkers. This study investigated the value of soluble stroma‐related molecules as PDAC biomarkers. In the first exploratory phase, 12 out of 38 molecules were associated with PDAC in a cohort of 25 PDAC patients and 16 healthy subjects. A second confirmatory phase on an independent cohort of 131 PDAC patients, 30 chronic pancreatitis patients, and 131 healthy subjects confirmed the PDAC association for MMP7, CCN2, IGFBP2, TSP2, sICAM1, TIMP1, and PLG. Multivariable logistic regression model identified biomarker panels discriminating respectively PDAC versus healthy subjects (MMP7 + CA19.9, AUC = 0.99, 99% CI = 0.98–1.00) (CCN2 + CA19.9, AUC = 0.96, 99% CI = 0.92–0.99) and PDAC versus chronic pancreatitis (CCN2 + PLG+FN+Col4 + CA19.9, AUC = 0.94, 99% CI = 0.88–0.99). Five molecules were associated with PanIN development in two GEM models of PDAC (PdxCre/LSL‐KrasG12D and PdxCre/LSL‐KrasG12D/+/LSL‐Trp53R172H/+), suggesting their potential for detecting early disease. These markers were also elevated in patient‐derived orthotopic PDAC xenografts and associated with response to chemotherapy. The identified stroma‐related soluble biomarkers represent potential tools for PDAC diagnosis and for monitoring treatment response of PDAC patients.https://doi.org/10.15252/emmm.201708741circulating biomarkersearly diagnosispancreatic cancertreatment evaluationtumor microenvironment |
| spellingShingle | Andrea Resovi Maria Rosa Bani Luca Porcu Alessia Anastasia Lucia Minoli Paola Allavena Paola Cappello Francesco Novelli Aldo Scarpa Eugenio Morandi Anna Falanga Valter Torri Giulia Taraboletti Dorina Belotti Raffaella Giavazzi Soluble stroma‐related biomarkers of pancreatic cancer EMBO Molecular Medicine circulating biomarkers early diagnosis pancreatic cancer treatment evaluation tumor microenvironment |
| title | Soluble stroma‐related biomarkers of pancreatic cancer |
| title_full | Soluble stroma‐related biomarkers of pancreatic cancer |
| title_fullStr | Soluble stroma‐related biomarkers of pancreatic cancer |
| title_full_unstemmed | Soluble stroma‐related biomarkers of pancreatic cancer |
| title_short | Soluble stroma‐related biomarkers of pancreatic cancer |
| title_sort | soluble stroma related biomarkers of pancreatic cancer |
| topic | circulating biomarkers early diagnosis pancreatic cancer treatment evaluation tumor microenvironment |
| url | https://doi.org/10.15252/emmm.201708741 |
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