Comparative Gene Expression Analysis of Epithelioid Pleural and Peritoneal Mesothelioma

Our plain-English summary of Comparative Gene Expression Analysis of Epithelioid Pleural and Peritoneal Mesothelioma, by R. Sparavelli, A.M. Poma, P. Faviana, et al (Cancers, 2026).

The study

• Authors: R. Sparavelli, A.M. Poma, P. Faviana, C. Ugolini, M. Lucchi, P.V. Lippolis, G. Alì, R. Bruno
• Journal: Cancers
• Published: 2026;18(18)
• Read it: PubMed · Publisher · Free full text

Abstract

Background/Objectives: Pleural and peritoneal mesothelioma (PL and PE) are aggressive diseases, accounting for 68.0-92.4% and 6.9-24.1% of all cases. To improve both diagnosis and management of these patients, a deeper knowledge and characterization of the molecular background are necessary. Although molecular profiling of PL has been largely investigated in recent years, much less is known about the genomic landscape of PE, due to its rarity. Here, we aim to compare gene expression profiling of pleural and peritoneal mesothelioma to underline main differences and to identify new potential histotype-specific biomarkers. Methods: We performed a gene expression analysis of 32 epithelioid PL and 21 epithelioid PE cases, diagnosed from 2017 to 2023 at the University Hospital of Pisa, using an nCounter custom panel including 117 target genes known for their crucial role in cancer. Results: PE, compared to PL, showed different expression levels of genes related to extracellular matrix modification (ECM), as collagen alteration, pro-inflammatory and angiogenic response (mediated by NF-κB). In detail, in PE we observed a significant upregulation of metalloproteinase-1 (MMP1), E-selectin (SELE), pappalysin-1 (PAPPA), estrogen receptor-2 (ESR2) and transportin-2 (TNPO2); and a downregulation of pyruvate kinase (PKM). Furthermore, BAP1 loss was associated with distinct gene deregulation in PE and PL; the only exception was ASS1 upregulation, which was observed in both histologies. These insights may help refine the utility of BAP1 as a biomarker. Conclusions: Deregulated genes in PE deserve further investigation as potential biomarkers, according to their biological role. In fact, MMPs and PAPPA impact migration ability and angiogenic response of mesothelioma, while PKM and ESR2 are usually investigated for their involvement in reprogramming of energy metabolism. The identification of histotype-specific biomarkers is warranted to improve mesothelioma management.

In plain English

This study compared gene activity in stored tumor samples from 32 patients with epithelioid pleural mesothelioma and 21 with epithelioid peritoneal mesothelioma, diagnosed 2017 to 2023 at the University Hospital of Pisa. The authors measured 117 cancer-related genes with a laboratory panel. Asbestos exposure was not studied as a cause. It was recorded as yes for 23 of the 32 pleural patients and was not available for any of the 21 peritoneal patients. The two tumor types had partly overlapping gene profiles. Six genes differed: MMP1, SELE, PAPPA, ESR2 and TNPO2 were more active, and PKM less active, in the peritoneal tumors. After allowing for age and sex, all six kept the same direction, but ESR2 and SELE no longer met the significance threshold. In exploratory analyses, loss of the BAP1 protein was linked to both shared and site-specific gene changes. Shared changes included lower activity of the BAP1 gene itself and higher activity of ASS1. The authors concluded that these genes warrant further investigation as possible biomarkers. They noted a small, single-centre sample and missing data on asbestos exposure, stage and treatment.

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 consecutive case series. Archived tumor tissue was tested with a 117-gene laboratory panel (nCounter) to compare gene expression between two tumor sites.
• Who was studied: 32 patients with epithelioid pleural mesothelioma and 21 patients with epithelioid peritoneal mesothelioma, diagnosed from 2017 to 2023 at the University Hospital of Pisa, Italy.
• Exposure: No asbestos exposure was analyzed. The comparison was tumor site (pleural vs peritoneal), with an additional exploratory comparison by BAP1 protein status. The authors state that asbestos exposure information was absent or too incomplete for adjustment.
• Main results:
  • Asbestos exposure, as given in Table 1: pleural group yes 23 (72%), no 3 (9%), not available 6 (19%). Peritoneal group not available for all 21 (100%).
  • Pleural and peritoneal samples showed a modest separation in gene profiles, with some overlap.
  • Compared with pleural tumors, peritoneal tumors showed lower PKM and higher MMP1, SELE, PAPPA, ESR2 and TNPO2. Significance was defined as a false discovery rate below 0.1.
  • After adjustment for age and sex, all six genes kept the same direction. ESR2 and SELE no longer met the significance threshold.
  • In an exploratory analysis (false discovery rate threshold 0.25), BAP1 loss was examined in four subgroups: pleural retained 12, pleural lost 19, peritoneal retained 11, peritoneal lost 9. In the peritoneal tumors, BAP1 loss was associated with reduced PTGIS, PDCD1, TOP2A and NDC80 and increased NME2.
  • In the pleural tumors, BAP1 loss was associated with lower BAP1 gene activity and altered ADAMTS8.
  • In both pleural and peritoneal tumors, BAP1 protein loss was associated with reduced BAP1 gene (mRNA) expression.
  • ASS1 expression was higher with BAP1 loss in both pleural and peritoneal tumors.
  • In the peritoneal tumors only, the Ki67 proliferation index correlated positively with several cell-cycle genes.
• The authors' conclusion: The authors concluded that the genes that differed in epithelioid peritoneal mesothelioma warrant further investigation as potential site-specific biomarkers. They also called for larger, independent cohorts to validate the findings.
• Limitations the authors state:
  • Small sample size from a single centre, which limited statistical power.
  • Data on asbestos exposure, disease stage and treatment history were missing or incomplete.
  • The differences should be read as associations with tumor site, not as definite effects of anatomical location.
  • Only 117 genes were measured, so important genes outside the panel could have been missed.
  • Contamination of the samples by non-tumor cells could not be fully excluded.
  • The BAP1 subgroup findings rest on small subgroups.
  • Ki67 analysis was possible only for the peritoneal cases.

Topics

Medical terms in this study, explained in our Lexicon: Epithelioid, Peritoneal Mesothelioma, Molecular Profiling, Biomarker, Collagen, BAP1, Mesothelioma.

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