Related Experiment Video
Updated: Jan 9, 2026
Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines
Published on: April 21, 2022
Multiomic, Histologic, and scRNA-seq Profiling of Pleural Mesothelioma Reveals Negative Prognosis Associated With a
David T Severson1, Samuel Freyaldenhoven2, Benjamin Wadowski2
1The Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program (www.impmeso.org), Division of Thoracic Surgery and the Lung Center, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts; Duke University Health System, Durham, North Carolina.
Introduction:
Multiomics pleural mesothelioma (PM) studies have identified prognostic molecular subsets of PM histologic types, epithelioid (ePM), biphasic (bPM), and sarcomatoid (sPM), defined by relative tumor cell content. However, the underlying biology modulating survival remains unknown.
Methods:
Using 93 samples from 40 patients, we performed single-cell RNA sequencing (scRNA-seq), bulk exome and RNA sequencing, optical genome mapping, spatial transcriptomics, and histologic analyses to identify candidate drivers and prognostic biomarkers of malignant cell (MC) state.
Results:
We identified a novel uncommitted MC state enriched in bPM tumors. Using inferred copy number variants, we observed all three MC states within individual clones suggesting MC state is not clonally restricted. We identified TGF-β and GAS6-AXL signaling as candidate MC state drivers for further study. Finally, we validated two prognostic MC state immunohistochemistry biomarkers, MEST (uncommitted) and MSLN (epithelioid).
Conclusions:
These multiomic, scRNA-seq analyses of primary patient tissues provide new candidate drivers of MC state and novel biomarkers to improve patient stratification. Further experimental exploration and clinical validation of these findings may reveal new treatment strategies and refine current clinical decision-making in PM.
