title: In silico analysis of the transportome in human pancreatic ductal adenocarcinoma.
abstract: The altered expression and/or activity of ion channels and transporters (transportome) have been associated with malignant behavior of cancer cells and were proposed to be a hallmark of cancer. However, the impact of altered transportome in epithelial cancers, such as pancreatic ductal adenocarcinoma (PDAC), as well as its pathophysiological consequences, still remains unclear. Here, we report the in silico analysis of 840 transportome genes in PDAC patients' tissues. Our study was focused on the transportome changes and their correlation with functional and behavioral responses in PDAC tumor and stromal compartments. The dysregulated gene expression datasets were filtered using a cut-off of fold-change values ≤-2 or ≥2 (adjusted p value ≤0.05). The dysregulated transportome genes were clearly associated with impaired physiological secretory mechanisms and/or pH regulation, control of cell volume, and cell polarity. Additionally, some down-regulated transportome genes were found to be closely linked to epithelial cell differentiation. Furthermore, the observed decrease in genes coding for calcium and chloride transport might be a mechanism for evasion of apoptosis. In conclusion, the current work provides a comprehensive overview of the altered transportome expression and its association with predicted PDAC malignancy with special focus on the epithelial compartment.
authors.affiliation: Institute for Experimental Cancer Research, Christian-Albrechts-University Kiel, UKSH, Campus Kiel, Arnold-Heller-Str. 3, 24105, Kiel, Germany. angela.zacca@email.uni-kiel.de.
authors.forename: A
authors.identifier: http://orcid.org/0000-0003-3972-7103
authors.initials: A
authors.lastname: Zaccagnino
authors.affiliation: Department of Surgery, University Clinic, Krankenhausstr. 12, 91054, Erlangen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Pilarsky
authors.affiliation: Institute for Experimental Cancer Research, Christian-Albrechts-University Kiel, UKSH, Campus Kiel, Arnold-Heller-Str. 3, 24105, Kiel, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Tawfik
authors.affiliation: Institute for Experimental Cancer Research, Christian-Albrechts-University Kiel, UKSH, Campus Kiel, Arnold-Heller-Str. 3, 24105, Kiel, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Sebens
authors.affiliation: Institute for Experimental Cancer Research, Christian-Albrechts-University Kiel, UKSH, Campus Kiel, Arnold-Heller-Str. 3, 24105, Kiel, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Trauzold
authors.affiliation: Section for Cell Biology and Physiology, Department of Biology, Faculty of Science, University of Copenhagen, Universitetsparken 13, 2100, Copenhagen, Denmark.
authors.forename: I
authors.initials: I
authors.lastname: Novak
authors.affiliation: Institute of Physiology II, University of Muenster, Robert-Koch-Str. 27 b, 48149, Muenster, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Schwab
authors.affiliation: Institute for Experimental Cancer Research, Christian-Albrechts-University Kiel, UKSH, Campus Kiel, Arnold-Heller-Str. 3, 24105, Kiel, Germany. holger.kalthoff@email.uni-kiel.de.
authors.forename: H
authors.initials: H
authors.lastname: Kalthoff
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019295:Computational Biology; D003198:Computer Simulation; D004848:Epithelium / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D007473:Ion Channels / Q000235:genetics* / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D059016:Tumor Microenvironment
chemical_list: D007473:Ion Channels
keywords: Chronic pancreatitis; Gene expression analysis; Ion channels; Pancreatic ductal adenocarcinoma; Transportome; Tumor stroma