Background: Although IGF2BP3 has been implicated in tumorigenesis and poor outcomes in multiple cancers, its role in soft-tissue sarcoma (STS) remains unknown. Preliminary data have suggested an association with IGF2BP3 expression among patients with well-differentiated/dedifferentiated liposarcoma (WD/DD LPS), a disease where molecular risk stratification is lacking. Methods: We examined the survival associations of IGF2BP3 via univariate and multivariate Cox regression in three unique datasets: (1) the Cancer Genome Atlas (TCGA), (2) an in-house gene microarray, and (3) an in-house tissue microarray (TMA). A fourth dataset, representing an independent in-house TMA, was used for validation. Results: Within the TCGA dataset, IGF2BP3 expression was a poor prognostic factor uniquely in DD LPS (OS 1.6 vs. 5.0 years,p= 0.009). Within the microarray dataset, IGF2BP3 expression in WD/DD LPS was associated with worse survival (OS 7.7 vs. 21.5 years,p= 0.02). IGF2BP3 protein expression also portended worse survival in WD/DD LPS (OS 3.7 vs. 13.8 years,p< 0.001), which was confirmed in our validation cohort (OS 2.7 vs. 14.9 years,p< 0.001). In the multivariate model, IGF2BP3 was an independent risk factor for OS, (HR 2.55,p= 0.034). Conclusion: IGF2BP3 is highly expressed in a subset of WD/DD LPS. Across independent datasets, IGF2BP3 is also a biomarker of disease progression and worse survival.
背景：尽管IGF2BP3已被证实与多种癌症的肿瘤发生及不良预后相关，但其在软组织肉瘤（STS）中的作用尚不明确。初步数据显示，在缺乏分子风险分层的分化良好/去分化脂肪肉瘤（WD/DD LPS）患者中，IGF2BP3表达可能与疾病进展存在关联。方法：我们通过单变量和多变量Cox回归分析，在三个独立数据集中评估了IGF2BP3与生存期的关联性：（1）癌症基因组图谱（TCGA）数据库，（2）内部基因微阵列数据集，（3）内部组织微阵列（TMA）数据集。另使用第四个独立内部TMA数据集进行验证。结果：在TCGA数据集中，IGF2BP3表达仅在DD LPS亚型中显示为不良预后因素（总生存期1.6年 vs 5.0年，p=0.009）。在微阵列数据集中，WD/DD LPS患者的IGF2BP3表达与较差的生存期相关（总生存期7.7年 vs 21.5年，p=0.02）。IGF2BP3蛋白表达同样预示WD/DD LPS患者生存期缩短（总生存期3.7年 vs 13.8年，p<0.001），这一发现在验证队列中得到确认（总生存期2.7年 vs 14.9年，p<0.001）。在多变量模型中，IGF2BP3是总生存期的独立风险因素（风险比2.55，p=0.034）。结论：IGF2BP3在部分WD/DD LPS肿瘤中高表达。跨独立数据集的分析表明，IGF2BP3可作为疾病进展和不良生存预后的生物标志物。
IGF2BP3 as a Prognostic Biomarker in Well-Differentiated/Dedifferentiated Liposarcoma
肿瘤(癌症)患者之家