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

Author:

Klingbeil Kyle D.123,Tang Jack Pengfei4ORCID,Graham Danielle S.12ORCID,Lofftus Serena Y.1,Jaiswal Amit Kumar5ORCID,Lin Tasha L.6,Frias Chris1,Chen Lucia Y.7,Nakasaki Manando5,Dry Sarah M.25,Crompton Joseph G.12ORCID,Eilber Fritz C.12ORCID,Rao Dinesh S.258,Kalbasi Anusha9ORCID,Kadera Brian E.12ORCID

Affiliation:

1. Department of Surgery, Division of Surgical Oncology, University of California, Los Angeles David Geffen School of Medicine, Los Angeles, CA 90049, USA

2. Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA

3. Molecular, Cellular, and Integrative Physiology Interdepartmental PhD Program, University of California, Los Angeles, Los Angeles, CA 90095, USA

4. University of California, Los Angeles David Geffen School of Medicine, Los Angeles, CA 90095, USA

5. Department of Pathology & Laboratory Medicine, University of California, Los Angeles David Geffen School of Medicine, Los Angeles, CA 90095, USA

6. Department of Medicine, Division of Hematology and Oncology, University of California, Los Angeles David Geffen School of Medicine, Los Angeles, CA 90095, USA

7. Department of Medicine, Statistics Core, University of California, Los Angeles David Geffen School of Medicine, Los Angeles, CA 90095, USA

8. Broad Stem Cell Research Center, University of California, Los Angeles, Los Angeles, CA 90095, USA

9. Department of Radiation Oncology, Stanford Cancer Institute, Stanford School of Medicine, Stanford, CA 94305, USA

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.

Funder

AK

Damon Runyon Cancer Research Foundation

BK

DR

National Institutes of Health

LC

National Center for Advancing Translational Science

TLL—Training Grant, Broad Stem Cell Research Center, UCLA

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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