Expression and prognostic significance of PDGF ligands and receptors across soft tissue sarcomas

Background While the anti-PDGFRA antibody olaratumab failed to confirm an impact on survival in unselected advanced soft tissue sarcoma (STS) patients, the level of expression and the prognosis of platelet-derived growth factor (PDGF) receptors and ligands in STS remain unclear. Patients and methods We analyzed PDGF ligands and receptors' expression levels in a series of 255 patients with different histologies of STS [gastrointestinal stromal tumor (GIST), myxoid liposarcoma (MLPS), sarcoma with complex genomics, synovial sarcoma (SyS)] with Agilent single-color micro-arrays. We explored expression levels as prognostic values in univariate and multivariate analysis using R software (version 3.4.2). Results Complex patterns of correlation of expression between ligands and receptors were observed for each histotype. PDGFA levels were highest in SyS and lowest in MLPS ( P < 4 × 10 −9 ), PDGFB and C levels were lower in GIST ( P < 2 × 10 −15 and P < 3 × 10 −9 ) while PDGFD expression was similar across histological subtypes. PDGF receptor (PDGFR) A expression was lowest in MLPS ( P < 0.002), whereas PDGFRB and L expressions were lowest in GIST and SyS ( P < 0.0004). Interestingly, high PDGFA expression levels were associated with higher risk of metastasis ( P  = 0.006), whereas PDGFD levels above average were associated with a reduced risk of metastasis ( P  = 0.01) in univariate and multivariate analysis. Conclusions The expression of PDGF ligands and receptors varies across sarcoma histological subtypes. PDGFA and D expression levels independently and inversely correlate with the risk of metastatic relapse.