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.
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Abbreviations
- CP:
-
Chronic pancreatitis
- CPS:
-
Chronic pancreatitis stroma
- EGFR:
-
Epidermal growth factor receptor
- ECM:
-
Extracellular matrix
- NE:
-
Normal epithelium
- NHE1:
-
Na+/H+ exchanger 1
- NHERF1:
-
Regulatory cofactor of Na+/H+ exchanger
- HCO3 − :
-
Bicarbonate
- PDAC:
-
Pancreatic ductal adenocarcinoma
- EMT:
-
Epithelial–mesenchymal transition
- TE:
-
Tumor epithelium
- TF:
-
Transcription factor
- TS:
-
Tumor stroma
- FC:
-
Fold change
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Acknowledgments
This work was funded by FP7 Marie Curie Initial Training Network “IonTraC” (Grant Agreement No. 289648). D. Tawfik was supported by the DAAD. We are grateful to Dr. Christian Röder, Institute for Experimental Cancer Research, Christian-Albrechts-University Kiel and UKSH Campus Kiel, for his kind support. Dr. Silke Szymczak, Institute of Medical Informatics and Statistics, Christian-Albrechts-University Kiel and UKSH Campus Kiel, for providing an introduction and overview of the biostatistics tools for microarray analysis.
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Special Issue: Ion Channels, Transporters and Cancer.
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Zaccagnino, A., Pilarsky, C., Tawfik, D. et al. In silico analysis of the transportome in human pancreatic ductal adenocarcinoma. Eur Biophys J 45, 749–763 (2016). https://doi.org/10.1007/s00249-016-1171-9
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DOI: https://doi.org/10.1007/s00249-016-1171-9