Tumor Microenvironment-Associated Immune-Related Genes for the Prognosis of Malignant Pleural Mesothelioma

Our plain-English summary of Tumor Microenvironment-Associated Immune-Related Genes for the Prognosis of Malignant Pleural Mesothelioma, by X. Xu, L. Cheng, Y. Fan, et al (Frontiers in Oncology, 2020).

The study

• Authors: X. Xu, L. Cheng, Y. Fan, W. Mao
• Journal: Frontiers in Oncology
• Published: 2020;10:544789
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a rare but highly aggressive thoracic malignancy. ESTIMATE algorithm-derived immune scores are commonly used to quantify the immune and stromal components in tumors. Thus, this algorithm may help determine the tumor microenvironment (TME)-related gene expression profile associated with tumor immunity. This study aimed at mining public databases to determine a potential correlation between differentially expressed genes (DEGs) and survival in patients with MPM. We categorized patients from the Gene Expression Omnibus database according to their immune/stromal scores into high- and low-score groups. Functional enrichment analysis and the construction of protein-protein interaction networks showed that the DEGs identified were primarily involved in the TME. Furthermore, we validated these genes in an independent cohort of patients with MPM from The Cancer Genome Atlas database. DEG analysis showed that 29 DEGs were cancer driver genes. Subsequently, 14 TME-related genes, which have been previously neglected, were shown to exhibit significant prognostic potential in MPM. In conclusion, immune/stromal scores are novel predictors of a poor prognosis in patients with MPM. We identified DEGs that are involved in immunity against MPM and may contribute to patient survival. Owing to their potential as prognostic factors for MPM, these 14 TME-related genes need to be studied in detail in the future.

Copyright © 2020 Xu, Cheng, Fan and Mao.

In plain English

This was a computer analysis of existing gene-activity data on malignant pleural mesothelioma (MPM). No new patients were studied; asbestos was not its focus. The authors used ESTIMATE, a method that predicts immune and stromal (supporting) cell levels in tumors from gene-activity data. They applied it to 55 tumor samples (41 with paired normal tissue) from the Gene Expression Omnibus. Comparing high- and low-scoring tumors, they found 74 genes that differed under both scores. They then used 87 MPM patients from The Cancer Genome Atlas, diagnosed 1999 to 2013, though not all appeared in each survival comparison. Median overall survival was 719 days with low stromal scores vs. 414 days with high (43 patients each), p = 0.006. It was 620 days with high immune scores (46 patients) vs. 434 days with low (38 patients), p = 0.015. Of 29 cancer-specific genes, 14 were associated with poor survival. The scores did not correlate with clinical features, including asbestos exposure history, except pathological T stage. The authors concluded the scores were useful for prognosis. They noted the genes were not confirmed in clinical samples from China.

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: Bioinformatic (computer-based) analysis of publicly available gene expression databases (GEO and TCGA), with survival analysis
• Who was studied: 55 MPM tumor samples, with paired normal tissue for 41 of them, from the Gene Expression Omnibus database (GSE51024). Validation used 87 patients with MPM from The Cancer Genome Atlas, initially diagnosed between 1999 and 2013. The article does not state a total for each survival comparison. Adding its group sizes gives 86 for stromal-score overall survival (43 + 43) and 84 for the other three comparisons (46 + 38, 40 + 44, 55 + 29).
• Exposure: Not an exposure study. The study examined tumor gene expression and immune/stromal scores. History of asbestos exposure was one of the clinical variables retrieved from TCGA, and no fiber types or doses were studied.
• Main results:
  • Comparing high- and low-score tumors in the GEO data, 74 genes were differentially expressed under both the immune and the stromal scores
  • TCGA patients: median overall survival was 719 days with low stromal scores (43 cases) vs. 414 days with high stromal scores (43 cases), p = 0.006 by log-rank test
  • TCGA patients: median relapse-free survival was 620 days with low stromal scores (40 cases) vs. 414 days with high stromal scores (44 cases), p = 0.022
  • TCGA patients: median overall survival was 620 days in the high-immune-score group (46 cases) vs. 434 days in the low-immune-score group (38 cases), p = 0.015
  • TCGA patients: median relapse-free survival was 629 days in the high-immune-score group (55 cases) vs. 365 days in the low-immune-score group (29 cases), p = 0.011
  • Of 29 cancer-specific genes, 14 immune-related genes were associated with poor overall and relapse-free survival, while 15 had no significant association with survival
  • No correlations were seen between clinicopathological characteristics (including history of asbestos exposure) and immune and/or stromal scores, except pathological T stage
• The authors' conclusion: The authors concluded that immune and stromal scores calculated with the ESTIMATE algorithm were useful in determining the prognosis of patients with MPM. They stated that high immune and low stromal scores predicted a good prognosis, and that the 14 genes need further study.
• Limitations the authors state:
  • Because mesothelioma is rare, the authors could not collect fresh clinical samples to verify the results
  • The involvement of these genes in MPM was not confirmed in clinical samples from China

Topics

Medical terms in this study, explained in our Lexicon: Tumor Microenvironment, Prognosis, Pleural Mesothelioma.

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