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

Dimitrios E Magouliotis; Nikos Sakellaridis; Konstantinos Dimas; Vasiliki S Tasiopoulou; Konstantina A Svokos; Alexis A Svokos; Dimitris Zacharoulis

doi:10.2174/1389202921666200316115631

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

Curr Genomics. 2020 Feb;21(2):119-127. doi: 10.2174/1389202921666200316115631.

Authors

Dimitrios E Magouliotis¹, Nikos Sakellaridis¹, Konstantinos Dimas¹, Vasiliki S Tasiopoulou¹, Konstantina A Svokos¹, Alexis A Svokos¹, Dimitris Zacharoulis¹

Affiliation

¹ 1Division of Surgery and Interventional Science, Faculty of Medical Sciences, UCL, London, UK and Department of Surgery, University of Thessaly, Biopolis, Larissa, Greece; 2Department of Pharmacology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, Larissa, Greece; 3Department of Pharmacology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, Larissa, Greece; 4Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, Larissa, Greece; 5The Warren Alpert Medical School of Brown University, Providence, RI, USA; 6Geisinger Medical Center, Danville, PA, USA; 7Department of Surgery, University Hospital of Larissa, Larissa, Greece.

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.

Keywords: Pancreatic cancer; adenocarcinoma; biomarker; chloride intracellular channel; clic; miRNA.