In Silico Transcriptomic Analysis of Wound-Healing-Associated Genes in Malignant Pleural Mesothelioma

Our plain-English summary of In Silico Transcriptomic Analysis of Wound-Healing-Associated Genes in Malignant Pleural Mesothelioma, by E. Rouka, E. Beltsios, D. Goundaroulis, et al (Medicina, 2019).

The study

• Authors: E. Rouka, E. Beltsios, D. Goundaroulis, G.D. Vavougios, E.I. Solenov, C. Hatzoglou, K.I. Gourgoulianis, S.G. Zarogiannis
• Journal: Medicina
• Published: 2019;55(6)
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background and objectives: Malignant pleural mesothelioma (MPM) is a devastating malignancy with poor prognosis. Reliable biomarkers for MPM diagnosis, monitoring, and prognosis are needed. The aim of this study was to identify genes associated with wound healing processes whose expression could serve as a prognostic factor in MPM patients. Materials and Methods: We used data mining techniques and transcriptomic analysis so as to assess the differential transcriptional expression of wound-healing-associated genes in MPM. Moreover, we investigated the potential prognostic value as well as the functional enrichments of gene ontologies relative to microRNAs (miRNAs) of the significantly differentially expressed wound-healing-related genes in MPM. Results: Out of the 82 wound-healing-associated genes analyzed, 30 were found significantly deregulated in MPM. Kaplan-Meier analysis revealed that low ITGAV gene expression could serve as a prognostic factor favoring survival of MPM patients. Finally, gene ontology annotation enrichment analysis pointed to the members of the hsa-miR-143, hsa-miR-223, and the hsa-miR-29 miRNA family members as important regulators of the deregulated wound healing genes. Conclusions: 30 wound-healing-related genes were significantly deregulated in MPM, which are potential targets of hsa-miR-143, hsa-miR-223, and the hsa-miR-29 miRNA family members. Out of those genes, ITGAV gene expression was a prognostic factor of overall survival in MPM. Our results highlight the role of impaired tissue repair in MPM development and should be further validated experimentally.

In plain English

This study did not collect new samples or measure asbestos exposure. Instead, the authors re-analyzed publicly available gene-activity (microarray) data from a dataset called GDS1220. They used surgically removed tissue from 40 malignant pleural mesothelioma cases and 9 controls (5 pleura and 4 lung samples) and looked at 82 genes linked to wound healing. Of these, 30 differed significantly between tumors and controls: 14 were more active and 16 less active in the tumors. One of these genes, ITGAV, was more active in tumors. Patients with low ITGAV activity had a median overall survival of 15.7 months, compared with 12 months for those with high activity (p = 0.0263). Data from The Cancer Genome Atlas pointed the same way (p = 0.001). Computer analysis predicted that the 30 genes might be targets of the microRNAs hsa-miR-143, hsa-miR-223 and the hsa-miR-29 family. The authors concluded that their results highlight the role of impaired tissue repair in mesothelioma development and should be further validated experimentally. They noted that tumor subtype data were not available.

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: In silico (computer-based) transcriptomic analysis of publicly available gene expression microarray data, with survival analysis and gene ontology/miRNA enrichment analysis
• Who was studied: Surgically excised samples from the GDS1220 dataset: 40 malignant pleural mesothelioma (MPM) cases and 9 controls (5 pleura and 4 lung samples). The Cancer Genome Atlas (TCGA) mesothelioma data were also used for survival analysis; the number of TCGA patients is not given. Analysis was performed in February 2019.
• Exposure: No asbestos or other fiber exposure was analyzed. The study compared the expression of 82 wound-healing-related genes in MPM tissue versus control tissue. The authors state that future work should take history of asbestos exposure into account.
• Main results:
  • Of 82 wound-healing-related genes analyzed, 30 were significantly differentially expressed in MPM compared with controls: 14 up-regulated and 16 down-regulated.
  • Ten further genes were significant in the initial comparison but not after correction for multiple testing.
  • In the GDS1220 data, MPM patients with low ITGAV expression had a median overall survival of 15.7 months versus 12 months for those with high expression (p = 0.0263).
  • Analysis of TCGA patient data via the PROGgeneV2 database also showed that low ITGAV expression favored survival in MPM patients (p = 0.001).
  • A regression model found a positive association between ITGAV and COL5A1 gene expression; the model explained 43.54% of the variability (adjusted R2 = 0.4354).
  • Enrichment analysis predicted that the 30 deregulated genes might be targets of hsa-miR-143, hsa-miR-223 and hsa-miR-29 family microRNAs. The biological functions identified related to cell locomotion, mobility and migration.
• The authors' conclusion: The authors concluded that ITGAV is a novel predictor of overall survival in MPM, and that their results highlight the role of impaired tissue repair in MPM development and should be further validated experimentally.
• Limitations the authors state:
  • Data on the histological subtype of the MPM specimens were not available in the GDS1220 dataset.
  • The authors state that the expression of these genes needs to be investigated in the clinical setting, taking into account MPM phenotype and asbestos exposure history, and that the results need experimental validation.

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, Prognosis, Biomarker, Overall Survival.

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• Gene expression profile of aquaporin 1 and associated interactors in malignant pleural mesothelioma — R. Jagirdar, E.I. Solenov, et al. (2013)
• Diagnostic potential of miR-126, miR-143, miR-145, and miR-652 in malignant pleural mesothelioma — M. Andersen, M. Grauslund, et al. (2014)
• Genomic and transcriptomic analyses identify a prognostic gene signature and predict response to therapy in pleural and peritoneal mesothelioma — N.U. Nair, Q. Jiang, et al. (2023)
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