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

Kyle D Klingbeil; Jack Pengfei Tang; Danielle S Graham; Serena Y Lofftus; Amit Kumar Jaiswal; Tasha L Lin; Chris Frias; Lucia Y Chen; Manando Nakasaki; Sarah M Dry; Joseph G Crompton; Fritz C Eilber; Dinesh S Rao; Anusha Kalbasi; Brian E Kadera

doi:10.3390/cancers15184489

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

Cancers (Basel). 2023 Sep 9;15(18):4489. doi: 10.3390/cancers15184489.

Authors

Kyle D Klingbeil^{1

2

3}, Jack Pengfei Tang⁴, Danielle S Graham^{1

2}, Serena Y Lofftus¹, Amit Kumar Jaiswal⁵, Tasha L Lin⁶, Chris Frias¹, Lucia Y Chen⁷, Manando Nakasaki⁵, Sarah M Dry^{2

5}, Joseph G Crompton^{1

2}, Fritz C Eilber^{1

2}, Dinesh S Rao^{2

5

8}, Anusha Kalbasi⁹, Brian E Kadera^{1

2}

Affiliations

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.

Keywords: IGF2BP3; IMP3; TCGA; dedifferentiated liposarcoma; gene microarray; liposarcoma; prognostic biomarker; soft-tissue sarcoma; tissue microarray; well-differentiated liposarcoma.

Abstract

Grants and funding