Title:In Silico Transcriptomic Analysis of the Chloride Intracellular Channels (CLIC) Interactome Identifies a Molecular Panel of Seven Prognostic Markers in Patients with Pancreatic Ductal Adenocarcinoma
VOLUME: 21 ISSUE: 2
Author(s):Dimitrios E. Magouliotis, Nikos Sakellaridis, Konstantinos Dimas, Vasiliki S. Tasiopoulou, Konstantina A. Svokos, Alexis A. Svokos and Dimitris Zacharoulis*
Affiliation:Division of Surgery and Interventional Science, Faculty of Medical Sciences, UCL, London, UK and Department of Surgery, University of Thessaly, Biopolis, Larissa, Department of Pharmacology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, Larissa, Department of Pharmacology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, Larissa, The Warren Alpert Medical School of Brown University, Providence, RI, Geisinger Medical Center, Danville, PA, Department of Surgery, University Hospital of Larissa, Larissa
Keywords:Pancreatic cancer, biomarker, clic, chloride intracellular channel, miRNA, adenocarcinoma.
Abstract:
Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis.
In this context, the identification of biomarkers regarding the PDAC diagnosis, monitoring, and prognosis
is crucial.
Objectives: The purpose of the current study was to investigate the differential gene expression profile
of the chloride intracellular channel (CLIC) gene family network in patients with PDAC, in order to
suggest novel biomarkers.
Methods: In silico techniques were used to construct the interactome of the CLIC gene family, identify
the differentially expressed genes (DEGs) in PDAC as compared to healthy controls, and evaluate
their potential prognostic role.
Results: Transcriptomic data of three microarray datasets were included, incorporating 114 tumor and
59 normal pancreatic samples. Twenty DEGs were identified; eight were up-regulated and twelve
were downregulated. A molecular signature of seven genes (Chloride Intracellular Channel 1 –
CLIC1; Chloride Intracellular Channel 3 – CLIC3; Chloride Intracellular Channel 4 – CLIC4; Ganglioside
Induced Differentiation Associated Protein 1 – GDAP1; Ganglioside Induced Differentiation
Associated Protein 1 Like 1 – GDAP1L1; Glutathione S-Transferase Pi 1 - GSTP1; Prostaglandin E
Synthase 2 – PTGES2) were identified as prognostic markers associated with overall survival. Positive
correlations were reported regarding the expression of CLIC1-CLIC3, CLIC4-CLIC5, and CLIC5-
CLIC6. Finally, gene set enrichment analysis demonstrated the molecular functions and miRNA families
(hsa-miR-122, hsa-miR-618, hsa-miR-425, and hsa-miR-518) relevant to the seven prognostic
markers.
Conclusion: These outcomes demonstrate a seven-gene molecular panel that predicts the patients’
prospective survival following pancreatic resection for PDAC.
