Centre Léon Bérard, Lyon, France.
University of Bordeaux, Bordeaux, France; Inserm U1218, Institut Bergonié, Bordeaux, France; Inserm UMR1037, Cancer Research Center of Toulouse, Toulouse, France; Institut Claudius Regaud, Toulouse, France.
ESMO Open. 2021 Feb;6(1):100037. doi: 10.1016/j.esmoop.2020.100037. Epub 2021 Jan 29.
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.
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).
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), PDGFB and C levels were lower in GIST (P < 2 × 10 and P < 3 × 10) 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.
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.
抗 PDGFRA 抗体奥沙拉单抗未能证实对未经选择的晚期软组织肉瘤（STS）患者的生存有影响，但血小板衍生生长因子（PDGF）受体和配体在 STS 中的表达水平和预后仍不清楚。
我们使用安捷伦单色彩微阵列分析了 255 例不同组织学类型的 STS [胃肠道间质瘤（GIST）、黏液样脂肪肉瘤（MLPS）、复杂基因组肉瘤、滑膜肉瘤（SyS）]患者中 PDGF 配体和受体的表达水平。我们使用 R 软件（版本 3.4.2）在单变量和多变量分析中探索了表达水平作为预后值。
每种组织类型的配体和受体之间的表达水平都呈现出复杂的相关模式。SyS 中 PDGFA 水平最高，MLPS 中水平最低（P < 4×10），GIST 中 PDGFB 和 C 水平较低（P < 2×10 和 P < 3×10），而 PDGFD 表达在组织学亚型之间相似。MLPS 中 PDGFR 表达最低（P < 0.002），而 GIST 和 SyS 中 PDGFRB 和 L 表达最低（P < 0.0004）。有趣的是，高 PDGFA 表达水平与转移风险增加相关（P = 0.006），而 PDGFD 水平高于平均值与转移风险降低相关（P = 0.01），在单变量和多变量分析中。
PDGF 配体和受体的表达在肉瘤组织学亚型中有所不同。PDGFA 和 D 的表达水平独立且呈负相关，与转移复发的风险相关。
