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High tumor cell platelet-derived growth factor receptor beta expression is associated with shorter survival in malignant pleural epithelioid mesothelioma. | LitMetric

AI Article Synopsis

  • Malignant pleural mesothelioma (MPM) has a complex structure with interactions between tumor cells and surrounding fibroblasts, but their roles in patient survival are not well understood.
  • A study involving 74 MPM patients identified that high levels of certain proteins, particularly platelet-derived growth factor receptor beta (PDGFRB) in tumor cells and secreted protein acidic and cysteine rich (SPARC) in fibroblasts, correlate with shorter survival.
  • The results suggest that PDGFRB and SPARC could serve as important markers for predicting patient outcomes and might be targeted in future therapies.

Article Abstract

Malignant pleural mesothelioma (MPM) has a rich stromal component containing mesenchymal fibroblasts. However, the properties and interplay of MPM tumor cells and their surrounding stromal fibroblasts are poorly characterized. Our objective was to spatially profile known mesenchymal markers in both tumor cells and associated fibroblasts and correlate their expression with patient survival. The primary study cohort consisted of 74 MPM patients, including 16 patients who survived at least 60 months. We analyzed location-specific tissue expression of seven fibroblast markers in clinical samples using multiplexed fluorescence immunohistochemistry (mfIHC) and digital image analysis. Effect on survival was assessed using Cox regression analyses. The outcome measurement was all-cause mortality. Univariate analysis revealed that high expression of secreted protein acidic and cysteine rich (SPARC) and fibroblast activation protein in stromal cells was associated with shorter survival. Importantly, high expression of platelet-derived growth factor receptor beta (PDGFRB) in tumor cells, but not in stromal cells, was associated with shorter survival (hazard ratio [HR] = 1.02, p < 0.001). A multivariable survival analysis adjusted for clinical parameters and stromal mfIHC markers revealed that tumor cell PDGFRB and stromal SPARC remained independently associated with survival (HR = 1.01, 95% confidence interval [CI] = 1.00-1.03 and HR = 1.05, 95% CI = 1.00-1.11, respectively). The prognostic effect of PDGFRB was validated with an artificial intelligence-based analysis method and further externally validated in another cohort of 117 MPM patients. In external validation, high tumor cell PDGFRB expression associated with shorter survival, especially in the epithelioid subtype. Our findings suggest PDGFRB and SPARC as potential markers for risk stratification and as targets for therapy.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363931PMC
http://dx.doi.org/10.1002/cjp2.218DOI Listing

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