Analysis of the correlation between Zeste enhancer homolog 2 (EZH2) mRNA expression and the prognosis of mesothelioma patients and immune infiltration

Our plain-English summary of Analysis of the correlation between Zeste enhancer homolog 2 (EZH2) mRNA expression and the prognosis of mesothelioma patients and immune infiltration, by K. Fan, C.L. Zhang, B.H. Zhang, et al (Scientific Reports, 2022).

The study

• Authors: K. Fan, C.L. Zhang, B.H. Zhang, M.Q. Gao, Y.C. Sun
• Journal: Scientific Reports
• Published: 2022;12(1):16583
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Mesothelioma lies one of the most malignant tumors, in which the identification of the corresponding biomarkers is extremely critical. This study aims to investigate the prognostic value of enhancer homolog 2 (EZH2) mRNA expression in mesothelioma patients accompanied with its immune infiltration analysis. Gene expression, clinical information and enrichment analysis were obtained based on the Cancer Genome Atlas (TCGA), the immune infiltration analysis and bioinformatics analysis were performed. Clinical information and gene expression were obtained from 86 patients with mesothelioma based on TCGA database. Survival analysis, GSEA enrichment analysis, and immune infiltration analysis of EZH2 expression were carried out using R (version 3.6.3) (statistical analysis and visualization). The correlation of EZH2 expression with immune cell infiltration in mesothelioma was analyzed according to the TIMER database (Fig. https://cistrome.shinyapps.io/timer/ ). A univariate and multivariate analysis of general data obtained from the TCGA database was performed, involving age, gender, stage, pathological type, and whether they had received radiotherapy, the results indicated the association of high expression of EZH2 with poor prognosis in mesothelioma patients, with the worse prognosis in the High group (HR = 2.75, 95% CI 1.68-4.52, P < 0.010). Moreover, ROC curves showed that EZH2 expression predicted 1-year survival with an AUC of 0.740, 2-year survival with an AUC of 0.756, and 3-year survival with an AUC of 0.692, suggesting a robust predictive effect of EZH2 expression on prognosis. KEGG pathway analysis indicated five pathways showing the strongest positive correlation with EZH2 expression: cell cycle, DNA replication, Cell adhesion molecules cams, Primary immuno deficiency, Tsate transduction, and five pathways showing the strongest negative correlation with EZH2 expression: Glycolysis gluconeogenesis, Drug metabolism, cytochrome P450, retinol metabolism, fatty acid metabolism ribosome. We investigated the correlation between EZH2 expression and the level of immune infiltration in mesothelioma tissues. The results indicated that EZH2 expression played a critical role in immune infiltration, of which the high expression was correlated with the reduced number of NK cells, Mast cells, and Th17 cells. Moreover, mesothelioma patients with high EZH2 expression differ from those with low EZH2 expression in their tumor immune microenvironment. EZH2, as a new prognostic biomarker for mesothelioma, contributes to elucidating how changes in the immune environment promote the development of mesothelioma. Further analysis, EZH2 may serve as a biological test to predict the prognosis of mesothelioma.

© 2022. The Author(s).

In plain English

This was a computer analysis of existing data from The Cancer Genome Atlas (TCGA). The authors examined EZH2 gene activity in tumors from 86 mesothelioma patients. They split them at the median into 43 high-expression and 43 low-expression patients. Reported survival was 26.3 (23 to 32.7) months in the low group and 13.7 (9.9 to 17.9) months in the high group; the ranges are not explained. The high group had a worse prognosis (hazard ratio 2.75, 95% CI 1.68 to 4.52). The authors also adjusted for age, gender, stage, tumor type and radiotherapy. After adjustment, high EZH2 expression remained associated with shorter survival (hazard ratio 2.63, 95% CI 1.02 to 6.79, P = 0.046). In the high group, estimated NK, mast and Th17 cell levels were lower, and T helper and Th2 cell levels were higher. Asbestos exposure history, a background characteristic only, was similar in both groups: 27 of 34 low-group and 29 of 36 high-group patients reported exposure. The authors concluded that high EZH2 expression predicts a poor prognosis and may serve as a prognostic indicator. They did not state any limitations.

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: Retrospective bioinformatics analysis of publicly available gene expression and clinical data (TCGA database); no new patients were examined
• Who was studied: 86 mesothelioma patients from the TCGA MESO project, split at the median EZH2 expression into 43 high-expression and 43 low-expression patients. Location and years of diagnosis are not stated, and the article does not say whether tumors were pleural or peritoneal.
• Exposure: The factor studied was EZH2 mRNA expression in tumor tissue (high vs low, split at the median). Asbestos exposure history was listed only as a background patient characteristic; no fiber types or doses are given.
• Main results:
  • Reported survival time was 26.3 (23 to 32.7) months in the low EZH2 expression group and 13.7 (9.9 to 17.9) months in the high expression group. The article does not say what the bracketed ranges represent.
  • The high EZH2 expression group had a worse prognosis than the low group: HR = 2.75, 95% CI 1.68 to 4.52, P less than 0.001.
  • In the univariate Cox analysis, EZH2 expression was associated with overall survival: HR = 2.35, 95% CI 1.62 to 3.42, P less than 0.001.
  • In the multivariate Cox analysis, which included age, gender, histological type, stage and radiation therapy, the authors reported EZH2 expression as an independent prognostic factor: HR = 2.63, 95% CI 1.02 to 6.79, P = 0.046. Table 2 prints this HR as 2.64.
  • ROC curves for EZH2 expression gave an AUC of 0.740 for 1-year survival, 0.756 for 2-year survival and 0.692 for 3-year survival.
  • Comparing 24 immune cell types between groups, the high EZH2 group had lower NK cells (P = 0.023), lower mast cells (P = 0.040) and lower Th17 cells (P = 0.005). It had higher T helper cells (P = 0.021) and higher Th2 cells (P less than 0.001).
  • Using TIMER, the authors reported positive correlations of EZH2 expression with B cells, CD4+ T cells and dendritic cells. The p-value printed for CD4+ T cells is 5.31 times 10 to the minus 2.
  • Pathway analysis found five pathways most positively correlated with EZH2 expression (cell cycle, DNA replication, cell adhesion molecules, primary immunodeficiency, taste transduction). Five were most negatively correlated (glycolysis/gluconeogenesis, drug metabolism cytochrome P450, retinol metabolism, fatty acid metabolism, ribosome).
  • Asbestos exposure history did not differ between groups (P = 1.000). In the low EZH2 group, 7 reported no exposure and 27 reported exposure; in the high group, 7 reported no exposure and 29 reported exposure. Percentages are of the 70 patients with this information.
• The authors' conclusion: The authors concluded that high EZH2 expression predicts a poor prognosis in mesothelioma and may serve as a prognostic indicator and target gene. They suggested the mechanism may be linked to immune infiltration and metabolism, and called for further exploration.

Topics

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

Medical terms in this study, explained in our Lexicon: Prognosis, Mesothelioma, Biomarker, Multivariate Analysis.

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