A panel of emerging EMT genes identified in malignant mesothelioma

Our plain-English summary of A panel of emerging EMT genes identified in malignant mesothelioma, by L. Wu, S. Amjad, H. Yun, et al (Scientific Reports, 2022).

The study

• Authors: L. Wu, S. Amjad, H. Yun, S. Mani, M. de Perrot
• Journal: Scientific Reports
• Published: 2022;12(1):1007
• Cited by: 28 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma (MESO) is a highly aggressive cancer with poor prognosis. Epithelial-mesenchymal transition (EMT) is a critical process in malignancies involved in tumor angiogenesis, progression, invasion and metastasis, immunosuppressive microenvironment and therapy resistance. However, there is a lack of specific biomarkers to identify EMT in MESO. Biphasic MESO with dual phenotypes could be an optimal model to study EMT process. Using a powerful EMTome to investigate EMT gene signature, we identified a panel of EMT genes COL5A2, ITGAV, SPARC and ACTA2 in MESO. In combination with TCGA database, Timer2.0 and other resources, we observed that overexpression of these emerging genes is positively correlated with immunosuppressive infiltration, and an unfavorable factor to patient survival in MESO. The expression of these genes was confirmed in our patients and human cell lines. Our findings suggest that these genes may be novel targets for therapeutics and prognosis in MESO and other types of cancers.

© 2022. The Author(s).

In plain English

This was a laboratory and database study of gene activity in malignant mesothelioma. It did not study asbestos or any other exposure. The authors injected mouse mesothelioma cells (RN5) into the abdomens of 40 female mice and measured which genes became more active over 8 weeks. They identified 72 tumor-cell genes and 55 non-tumor-cell genes. Epithelial-mesenchymal transition (EMT), a process in which epithelial cells adopt mesenchymal features, was the top pathway in both sets. They then chose four genes (COL5A2, ITGAV, SPARC and ACTA2) and checked them in a public mesothelioma data set called TCGA: 62 epithelioid, 23 biphasic and 2 sarcomatoid tumors. All four genes were more active in non-epithelioid tumors. Patients with higher activity of each gene had shorter median survival. For COL5A2 it was 13.61 versus 24.89 months (hazard ratio 2.318, 95% CI 1.424 to 3.774). Higher activity was also correlated with immune cells the authors describe as immunosuppressive. Among five patients with pleural mesothelioma, the one biphasic tumor showed the highest expression. The authors concluded these genes may be potential treatment targets and prognostic indicators. They noted that only two sarcomatoid cases were 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: Laboratory and bioinformatics study: a mouse tumor model with microarray and single-cell RNA sequencing, analysis of public databases (TCGA, EMTome, Timer2.0), and checks in patient biopsies and human cell lines
• Who was studied: 40 female C57BL/6 mice injected with RN5 mouse mesothelioma cells. The TCGA mesothelioma cohort: 62 epithelioid, 23 biphasic and 2 sarcomatoid patients. Five untreated patients with malignant pleural mesothelioma at University Health Network, Toronto. Two human mesothelioma cell lines (CRL-5915, epithelioid; CRL-5946, sarcomatoid).
• Exposure: No asbestos or other environmental exposure was studied. The study examined expression levels of EMT-related genes (COL5A2, ITGAV, SPARC, ACTA2) in mesothelioma.
• Main results:
  • Combining three mouse data sets, the authors identified 55 non-tumor cell genes and 72 tumor cell genes.
  • EMT was the top hallmark pathway in both gene sets: 12 of 72 tumor cell genes and 11 of 55 non-tumor cell genes.
  • In the TCGA mesothelioma cohort, all four genes (COL5A2, ITGAV, SPARC, ACTA2) had significantly higher mRNA expression in non-epithelioid (biphasic and sarcomatoid) than in epithelioid tumors (p less than 0.05 for all comparisons).
  • In the whole TCGA mesothelioma cohort, patients with high COL5A2 had median survival of 13.61 months versus 24.89 months for low COL5A2 (hazard ratio 2.318, 95% CI 1.424 to 3.774). High and low were defined by a median split.
  • Whole cohort, ITGAV: median survival 15.02 months for high versus 24.07 months for low expression (hazard ratio 1.791, 95% CI 1.116 to 2.875).
  • Whole cohort, SPARC: median survival 13.61 months for high versus 26.14 months for low expression (hazard ratio 2.337, 95% CI 1.441 to 3.791).
  • Whole cohort, ACTA2: median survival 14.17 months for high versus 24.36 months for low expression (hazard ratio 2.035, 95% CI 1.266 to 3.270).
  • Among epithelioid-subtype patients only, high COL5A2 was linked with median survival of 15.22 months versus 28.37 months for low COL5A2 (hazard ratio 2.823, 95% CI 1.566 to 5.088). The other three genes also correlated with survival in this subtype.
  • In the mesothelioma cohort, gene expression correlated positively with macrophages, Th2 and Treg cells, which the authors call immunosuppressive enrichment, and negatively with NKT and Th17 cells.
  • Among the five patient biopsies, the one patient with biphasic subtype had the highest expression of the four genes. The other cases were epithelioid.
• The authors' conclusion: The authors concluded that COL5A2, ITGAV, SPARC and ACTA2 may be a panel of emerging EMT genes in mesothelioma. They wrote that these genes may be potential therapeutic targets and prognostic indicators.
• Limitations the authors state:
  • The TCGA database contained only two sarcomatoid mesothelioma patients, which limited comparison between biphasic and sarcomatoid tumors.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Prognosis, Angiogenesis, Metastasis, Biomarker, Biphasic Mesothelioma.

Related studies

• Mesothelioma cell heterogeneity identified by single cell RNA sequencing — L. Wu, Z. Wang, et al. (2025)
• Differentially expressed alternatively spliced genes in malignant pleural mesothelioma identified using massively parallel transcriptome sequencing — L. Dong, R.V. Jensen, et al. (2009)
• Omics Overview of the SPARC Gene in Mesothelioma — L. Wu, M. de Perrot (2023)
• Novel genes and pathways modulated by syndecan-1: implications for the proliferation and cell-cycle regulation of malignant mesothelioma cells — T. Szatmári, F. Mundt, et al. (2012)
• Comprehensive analysis reveals prognostic gene set that could impacts the response to chemotherapy and immunotherapy outcomes in malignant pleural mesothelioma — J. Li, H. He, et al. (2025)
• Prognostic Value of EMT Gene Signature in Malignant Mesothelioma — L. Wu, K. Yoshihara, et al. (2023)

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