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Serum Cytokine Profile in Patients With Pancreatic Cancer

Torres, Carolina PhD*; Perales, Sonia PhD*; Alejandre, María José PhD*; Iglesias, José PhD*; Palomino, Rogelio J. PhD*; Martin, Miguel PhD; Caba, Octavio PhD; Prados, José C. PhD, MD§; Aránega, Antonia PhD, MD§; Delgado, Juan R. MD; Irigoyen, Antonio PhD, MD; Ortuño, Francisco M. PhD; Rojas, Ignacio PhD; Linares, Ana PhD*

doi: 10.1097/MPA.0000000000000155
Original Articles

Objective Pancreatic ductal adenocarcinoma is a deadly disease because of late diagnosis and chemoresistance. We aimed to find a panel of serum cytokines representing diagnostic and predictive biomarkers for pancreatic cancer.

Methods A cytokine antibody array was performed to simultaneously identify 507 cytokines in sera of patients with pancreatic cancer and healthy controls. The nonparametric Mann-Whitney U test was used to pairwise compare the controls, the pretreated patients, and the posttreated patients. Fold changes greater than or equal to 1.5 or less than or equal to 1/1.5 were considered significant. Receiver operating characteristic curves were used to assess the performance of the model. A leave-one-out cross-validation was used for estimating prediction error.

Results Comparing the sera of pretreated patients against the control samples, the cytokines fibroblast growth factor 10 (FGF-10/keratinocyte growth factor-2 (KGF-2), chemokine (C-X-C motif) ligand 11 interferon inducible T cell alpha chemokine (I-TAC)/chemokine [C-X-C motif] ligand 11 (CXCL11), oncostatin M (OSM), osteoactivin/glycoprotein nonmetastatic melanoma protein B, and stem cell factor (SCF) were found significantly overexpressed. Besides, the cytokines CD30 ligand/tumor necrosis factor superfamily, member 8 (TNFSF8), chordin-like 2, FGF-10/KGF-2, growth/differentiation factor 15, I-TAC/CXCL11, OSM, and SCF were differentially expressed in response to treatment.

Conclusions We propose a role for FGF-10/KGF-2, I-TAC/CXCL11, OSM, osteoactivin/glycoprotein nonmetastatic melanoma protein B, and SCF as novel diagnostic biomarkers. CD30 ligand/TNFSF8, chordin-like 2, FGF-10/KGF-2, growth/differentiation factor 15, I-TAC/CXCL11, OSM, and SCF might represent as predictive biomarkers for gemcitabine and erlotinib response of patients with pancreatic cancer.

From the *Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada; †Department of Molecular Oncology, Pfizer-University of Granada Center for Genomics and Oncological Research, Granada; ‡Department of Health Sciences, University of Jaen, Jaen; §Department of Human Anatomy and Embryology, University of Granada; ∥Oncology Service, Virgen de las Nieves Hospital; and ¶Department of Computer Architecture and Computer Technology, University of Granada, Granada, Spain.

Received for publication May 20, 2013; accepted April 1, 2014.

Reprints: Sonia Perales, PhD, Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Avenida Fuentenueva s/n, 18071, Granada, Spain (e-mail: sopero@ugr.es).

This study was supported by Roche Farma S.A. (REF H/OH-TAR-10/131 and REF H/OH-TRR-08/59) and Instituto de Salud Carlos III (clinical trial REF EC08/00009).

The authors declare no conflict of interest.

© 2014 by Lippincott Williams & Wilkins.