Refining classification of malignant pleural mesothelioma reveals its Achilles' heel

Our plain-English summary of Refining classification of malignant pleural mesothelioma reveals its Achilles' heel, by I.S. Pateras (EBioMedicine, 2019).

The study

• Author: I.S. Pateras
• Journal: EBioMedicine
• Published: 2019;48:3-4
• Type of article: Letter
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

In plain English

This is a short commentary, not an original study. The author discussed a separate study by Alcala and colleagues, published in the same journal, which reanalysed gene-activity data from two earlier studies of malignant pleural mesothelioma. The commentary does not mention asbestos and gives no patient numbers. As the author described it, Alcala and colleagues treated tumours as a continuum rather than as separate types. Two summary measures of gene activity, capturing 11% and 8% of the variation, gave a statistically significant prediction of survival. The first was related to the standard tissue subtypes. The second was independent of them and was independently associated with survival. This two-measure model predicted survival better than models based on tissue subtype. Three tumour profiles were described. A hot profile and a cold profile were both linked to non-epithelioid subtypes and to poor survival. A VEGFR2-positive, VISTA-positive profile was enriched for epithelioid tumours and had a favorable prognosis. The gene-activity results were checked against protein levels in a replication series. The author concluded that the present classification cannot predict the most effective treatments and that the study opens a window for new targeted treatments.

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: Commentary on another published study (Alcala et al., EBioMedicine 2019); it reports no original data
• Who was studied: As described in the commentary, Alcala et al. analysed transcriptomic (gene expression) data from two earlier high-throughput studies of malignant pleural mesothelioma (Bueno et al. 2016; Hmeljak et al. 2018). The commentary gives no number of patients.
• Main results:
  • As described by the commentary author, Alcala et al. found that a survival model using the first two principal components of gene expression (capturing 11% and 8% of variance, from the 7145 most variable genes) gave a statistically significant prediction of survival
  • According to the commentary, in Alcala et al. the first component was related to the classic tissue subtyping. The second was independent of the tissue classification and was independently associated with survival.
  • According to the commentary, the two-dimensional model in Alcala et al. was better at predicting survival than models based on tissue classification
  • According to the commentary, Alcala et al. described a "hot" profile and a "cold" profile, both linked to non-epithelioid subtypes and poor prognosis or survival. They also described VEGFR2+/VISTA+ tumours, enriched for epithelioid tumours, with a favorable prognosis.
  • According to the commentary, the gene-expression (RNA-seq) results from the discovery series in Alcala et al. were validated in a replication series using protein expression of 5 genes (VEGFR3, VEGFR2, CD8, PD-L1 and VISTA)
• The authors' conclusion: The commentary author concluded that the present classification of malignant pleural mesothelioma cannot predict the most effective treatments. The author also concluded that the Alcala et al. study highlights the angiogenesis-immune interaction, opening a window for new targeted treatments.

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.

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