Soluble stroma-related biomarkers of pancreatic cancer

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalEMBO Molecular Medicine
Volume10
Issue number8
DOIs
Publication statusPublished - Aug 2018

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Adenocarcinoma
Biomarkers
Area Under Curve
Healthy Volunteers
Chronic Pancreatitis
Logistic Models
Heterografts
Drug Therapy

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Soluble stroma-related biomarkers of pancreatic cancer. / Resovi, Andrea; Bani, Maria Rosa; Porcu, Luca; Anastasia, Alessia; Minoli, Lucia; Allavena, Paola; Cappello, Paola; Novelli, Francesco; Scarpa, Aldo; Morandi, Eugenio; Falanga, Anna; Torri, Valter; Taraboletti, Giulia; Belotti, Dorina; Giavazzi, Raffaella.

In: EMBO Molecular Medicine, Vol. 10, No. 8, 08.2018.

Research output: Contribution to journalArticle

Resovi, A, Bani, MR, Porcu, L, Anastasia, A, Minoli, L, Allavena, P, Cappello, P, Novelli, F, Scarpa, A, Morandi, E, Falanga, A, Torri, V, Taraboletti, G, Belotti, D & Giavazzi, R 2018, 'Soluble stroma-related biomarkers of pancreatic cancer', EMBO Molecular Medicine, vol. 10, no. 8. https://doi.org/10.15252/emmm.201708741
Resovi, Andrea ; Bani, Maria Rosa ; Porcu, Luca ; Anastasia, Alessia ; Minoli, Lucia ; Allavena, Paola ; Cappello, Paola ; Novelli, Francesco ; Scarpa, Aldo ; Morandi, Eugenio ; Falanga, Anna ; Torri, Valter ; Taraboletti, Giulia ; Belotti, Dorina ; Giavazzi, Raffaella. / Soluble stroma-related biomarkers of pancreatic cancer. In: EMBO Molecular Medicine. 2018 ; Vol. 10, No. 8.
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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.",
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T1 - Soluble stroma-related biomarkers of pancreatic cancer

AU - Resovi, Andrea

AU - Bani, Maria Rosa

AU - Porcu, Luca

AU - Anastasia, Alessia

AU - Minoli, Lucia

AU - Allavena, Paola

AU - Cappello, Paola

AU - Novelli, Francesco

AU - Scarpa, Aldo

AU - Morandi, Eugenio

AU - Falanga, Anna

AU - Torri, Valter

AU - Taraboletti, Giulia

AU - Belotti, Dorina

AU - Giavazzi, Raffaella

N1 - © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

PY - 2018/8

Y1 - 2018/8

N2 - 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.

AB - 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.

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