IGF2BP3 as a Prognostic Biomarker in Well-Differentiated/Dedifferentiated Liposarcoma

SIMPLE SUMMARY: Soft-tissue sarcoma (STS) is a rare cancer representing hundreds of unique subtypes. The prognosis of STS is heterogeneous, with few predictive biomarkers available beyond histologic subtype. IGF2BP3 is an RNA-binding protein that has recently been implicated in oncogenesis and tumor progression among various cancers. However, its association with STS has not been previously reported. In this study, we aimed to evaluate the expression and prognostic value of IGF2BP3 in STS. We found IGF2BP3 to be uniquely associated with poor survival among well-differentiated/dedifferentiated liposarcoma, a common subtype of STS, suggesting its role as a novel prognostic biomarker in this disease. ABSTRACT: 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.