Redefining malignant pleural mesothelioma types as a continuum uncovers immune-vascular interactions.

ABSTRACT:

Background

Malignant Pleural Mesothelioma (MPM) is an aggressive disease related to asbestos exposure, with no effective therapeutic options.

Methods

We undertook unsupervised analyses of RNA-sequencing data of 284 MPMs, with no assumption of discreteness. Using immunohistochemistry, we performed an orthogonal validation on a subset of 103 samples and a biological replication in an independent series of 77 samples.

Findings

A continuum of molecular profiles explained the prognosis of the disease better than any discrete model. The immune and vascular pathways were the major sources of molecular variation, with strong differences in the expression of immune checkpoints and pro-angiogenic genes; the extrema of this continuum had specific molecular profiles: a "hot" bad-

SUBMITTER: Alcala N 

PROVIDER: S-EPMC6838392 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature