Transcriptional over-expression of chloride intracellular channels 3 and 4 in malignant pleural mesothelioma

Our plain-English summary of Transcriptional over-expression of chloride intracellular channels 3 and 4 in malignant pleural mesothelioma, by V. Tasiopoulou, D. Magouliotis, E.I. Solenov, et al (Computational Biology and Chemistry, 2015).

The study

• Authors: V. Tasiopoulou, D. Magouliotis, E.I. Solenov, G. Vavougios, P.A. Molyvdas, K.I. Gourgoulianis, C. Hatzoglou, S.G. Zarogiannis
• Journal: Computational Biology and Chemistry
• Published: 2015;59 Pt A:111-6
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Chloride Intracellular Channels (CLICs) are contributing to the regulation of multiple cellular functions. CLICs have been found over-expressed in several malignancies, and therefore they are currently considered as potential drug targets. The goal of our study was to assess the gene expression levels of the CLIC's 1-6 in malignant pleural mesothelioma (MPM) as compared to controls.

Methods: We used gene expression data from a publicly available microarray dataset comparing MPM versus healthy tissue in order to investigate the differential expression profile of CLIC 1-6. False discovery rates were calculated and the interactome of the significantly differentially expressed CLICs was constructed and Functional Enrichment Analysis for Gene Ontologies (FEAGO) was performed.

Results: In MPM, the gene expressions of CLIC3 and CLIC4 were significantly increased compared to controls (p=0.001 and p<0.001 respectively). A significant positive correlation between the gene expressions of CLIC3 and CLIC4 (p=0.0008 and Pearson's r=0.51) was found. Deming regression analysis provided an association equation between the CLIC3 and CLIC4 gene expressions: CLIC3=4.42CLIC4-10.07.

Conclusions: Our results indicate that CLIC3 and CLIC4 are over-expressed in human MPM. Moreover, their expressions correlate suggesting that they either share common gene expression inducers or that their products act synergistically. FAEGO showed that CLIC interactome might contribute to TGF beta signaling and water transport.

Copyright © 2015 Elsevier Ltd. All rights reserved.

In plain English

This was a computer-based reanalysis of earlier published gene-activity data. It did not study asbestos exposure. The authors used microarray data from one previous study (the Gordon mesothelioma study) in the Oncomine database. That study covered 40 patients with malignant pleural mesothelioma and 9 healthy tissue samples (5 pleural and 4 lung). The authors compared the activity of genes for chloride intracellular channels CLIC1 to CLIC5; CLIC6 data were not available. CLIC3 (p = 0.0007) and CLIC4 (p = 0.0003) were significantly more active in the mesothelioma samples than in the healthy samples. CLIC1, CLIC2 and CLIC5 did not differ significantly. In the mesothelioma patients, CLIC3 and CLIC4 activity rose together (Pearson r = 0.51, p = 0.001). Gene-interaction databases linked 3 genes to CLIC3 and 12 to CLIC4, with one gene (DNM1) shared. This combined network was enriched for TGF-beta and related signaling processes and, in predictions based on other organisms, for water transport. The authors concluded that CLIC3 and CLIC4 are up-regulated in this cancer, and they said laboratory experiments are needed to confirm the findings.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Computational reanalysis of a publicly available gene expression (microarray) dataset, with gene-interaction network and gene-function enrichment analysis
• Who was studied: Samples from one earlier study (the Gordon Mesothelioma study, 2005) held in the Oncomine database: 40 patients with malignant pleural mesothelioma and 9 healthy samples (5 pleural and 4 lung derived). The analyses were performed in February 2013.
• Exposure: No asbestos exposure was studied. The study compared expression of the chloride intracellular channel genes CLIC1 to CLIC5 between mesothelioma and healthy tissue; CLIC6 data were not available.
• Main results:
  • CLIC3 gene expression was significantly higher in mesothelioma samples than in healthy controls (p = 0.0007)
  • CLIC4 gene expression was significantly higher in mesothelioma samples than in controls (p = 0.0003)
  • False discovery rate values supported these results: CLIC3 q = 0.007; CLIC4 q = 0.019
  • CLIC1 (p = 0.18), CLIC2 (p = 0.11) and CLIC5 (p = 0.40) did not differ significantly between mesothelioma and healthy samples
  • In mesothelioma patients, CLIC3 expression correlated positively with CLIC4 expression (p = 0.001, Pearson r = 0.51), described by the equation CLIC3 = 4.42 CLIC4 minus 10.07
  • Gene-interaction analysis found 3 genes interacting with CLIC3 and 12 with CLIC4, with only one gene, DNM1 (dynamin 1), common to both
  • The combined CLIC3 and CLIC4 network was enriched for processes related to BMP, TGF-beta and serine threonine kinase pathways; predictions based on genes in other organisms showed enrichment for transmembrane water transport and actin remodeling
• The authors' conclusion: The authors concluded that CLIC3 and CLIC4 are up-regulated in malignant pleural mesothelioma. They wrote that this seems to implicate a pathway that may be associated with the disease's phenotype and potentially its severity.
• Limitations the authors state:
  • The authors stated that functional laboratory experiments are needed to validate and explain their findings
  • The authors stated that the possible role of CLIC3 and CLIC4 in a shift toward the more aggressive sarcomatoid type requires experimental validation, since no data exist on CLICs and mesothelioma

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Discovery.

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