Randomized Clinical Trial
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Aug 15, 2016; 8(8): 635-641
Published online Aug 15, 2016. doi: 10.4251/wjgo.v8.i8.635
Utility of different serum fibrosis markers in diagnosing patients with chronic pancreatitis and pancreatic adenocarcinoma
Anna Kozak, Renata Talar-Wojnarowska, Aleksandra Kaczka, Anna Borkowska, Leszek Czupryniak, Ewa Małecka-Panas, Anita Gąsiorowska
Anna Kozak, Renata Talar-Wojnarowska, Aleksandra Kaczka, Ewa Małecka-Panas, Anita Gąsiorowska, Department of Digestive Tract Diseases, Medical University of Lodz, 90-153 Lodz, Poland
Anna Borkowska, Leszek Czupryniak, Department of Diabetology and Metabolic Diseases, Medical University of Lodz, 92-213 Lodz, Poland
Author contributions: Kozak A performed the systematic search of the literature, conducted statistical analysis and wrote the manuscript; Talar-Wojnarowska R, Kaczka A and Czupryniak L contributed equally to the acquisition and analysis of data; Borkowska A carried out the laboratory part of the project; Małecka-Panas E revised the article critically; Gąsiorowska A designed the study and reviewed the final version of the text.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of the Medical University of Lodz (RNN/146/15/KE).
Informed consent statement: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors declare no potential conflicting interests related to this paper.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Kozak Anna, MD, Department of Digestive Tract Diseases, Medical University of Lodz, Kopcinskiego 22, 90-153 Lodz, Poland. annak.kozak@gmail.com
Telephone: +48-426-776667 Fax: +48-678-6480
Received: February 1, 2016
Peer-review started: February 2, 2016
First decision: March 14, 2016
Revised: May 21, 2016
Accepted: June 14, 2016
Article in press: June 16, 2016
Published online: August 15, 2016
Abstract

AIM: To estimate the levels of serum cytokines in chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) patients in order to evaluate their usefulness as possible biomarkers.

METHODS: The study included 167 Caucasian patients: 74 with PDAC (28 men and 42 women, aged 30-88 years), 78 with CP (50 men and 21 women, aged 20-79 years) and 15 age-matched healthy controls hospitalized in the Department of Digestive Tract Diseases, Medical University of Lodz, Poland between 2006 and 2013. Serum MCP-1, transforming growth factor (TGF)-β1, HA and s-Fr were measured in patients with CP (n = 78), PDAC (n = 74) and healthy controls (n = 15) using ELISA (Corgenix United Kingdom Ltd R and D Systems). The severity of CP was assessed according to the Cambridge classification.

RESULTS: Both patients with CP and PDAC had a significantly higher mean TGF-β1 serum level (1066 ± 582 and 888 ± 356 vs 264 ± 93, P < 0.0001), mean s-Fr (2.42 ± 1.385 and 2.41 ± 1.275 vs 0.6 ± 0.370, P < 0.0001) and mean HA (199 ± 254 and 270 ± 358 vs 40 ± 26, P < 0.0001) compared to controls. There was no difference in mean MCP-1 between all the groups. There were no significant differences in any cytokine levels between the PC and PDAC groups. No significant differences between serum cytokines depending on age, gender or smoking status were found in CP patients. Mean s-Fr concentration was significantly higher in CP, lasting longer than 5 years compared to those with a shorter disease clinical course (2.639 ± 1.125 vs 1.870 ± 0.970, P < 0.03). There was no correlation between tumor size, localization or TNM classification and serum TGF-β1, MCP-1, s-Fr and HA levels in patients with PDAC. No significant differences between cytokines depending on diabetes presence in CP were found. Nevertheless, mean serum TGF-β1 concentration in PDAC patients was higher in those with diabetes compared to the remaining group (986 vs 839, P = 0.043).

CONCLUSION: Serum TGF-β1, s-Fr and HA may be considered additional diagnostic markers of CP and PDAC. TGF-β1 may be useful to predict endocrine insufficiency in PDAC.

Keywords: Fibrosis, Chronic pancreatitis, Soluble type fractalkine, Pancreatic adenocarcinoma, Transforming growth factor beta-1, Hyaluronic acid, Monocyte chemoattractant protein-1

Core tip: Fibrosis begins in an early stage of the disease in chronic pancreatitis and in pancreatic ductal adenocarcinoma. Cytokines such as transforming growth factor beta-1, hyaluronic acid, soluble fractalkine and monocyte chemoattractant protein-1 take part in connective tissue proliferation. It is essential to diagnose pancreatic diseases in the early stage in order to start an appropriate therapy. Cytokines can be useful clinical biomarkers.