Open AccessSoluble stroma‐related biomarkers of pancreatic cancer
Author(s) -
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
Publication year - 2018
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201708741
Subject(s) - stroma , pancreatic cancer , cancer , cancer research , medicine , computational biology , biology , pathology , oncology , immunohistochemistry
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 MMP 7, CCN 2, IGFBP 2, TSP 2, sICAM 1, TIMP 1, and PLG . Multivariable logistic regression model identified biomarker panels discriminating respectively PDAC versus healthy subjects ( MMP 7 + CA 19.9, AUC = 0.99, 99% CI = 0.98–1.00) ( CCN 2 + CA 19.9, AUC = 0.96, 99% CI = 0.92–0.99) and PDAC versus chronic pancreatitis ( CCN 2 + PLG + FN +Col4 + CA 19.9, AUC = 0.94, 99% CI = 0.88–0.99). Five molecules were associated with Pan IN development in two GEM models of PDAC (PdxCre/ LSL ‐Kras G12D and PdxCre/ LSL ‐Kras G12D/+ / LSL ‐Trp53 R172H/+ ), 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.