IGF2BP3 as a Prognostic Biomarker in Well-Differentiated/Dedifferentiated Liposarcoma-Reference-Cited by-同舟云学术

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

Published:2023-09-09 Issue:18 Volume:15 Page:4489
ISSN:2072-6694
Container-title:Cancers
language:en
Short-container-title:Cancers

Author:

Klingbeil Kyle D.¹²³,Tang Jack Pengfei⁴^ORCID,Graham Danielle S.¹²^ORCID,Lofftus Serena Y.¹,Jaiswal Amit Kumar⁵^ORCID,Lin Tasha L.⁶,Frias Chris¹,Chen Lucia Y.⁷,Nakasaki Manando⁵,Dry Sarah M.²⁵,Crompton Joseph G.¹²^ORCID,Eilber Fritz C.¹²^ORCID,Rao Dinesh S.²⁵⁸,Kalbasi Anusha⁹^ORCID,Kadera Brian E.¹²^ORCID

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

Damon Runyon Cancer Research Foundation

National Institutes of Health

National Center for Advancing Translational Science

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

Publisher

MDPI AG

Subject

Cancer Research,Oncology

Link

https://www.mdpi.com/2072-6694/15/18/4489/pdf

Reference70 articles.

1. The role of the oncofetal IGF2 mRNA-binding protein 3 (IGF2BP3) in cancer;Lederer;Semin. Cancer Biol.,2014

2. Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs): Post-transcriptional drivers of cancer progression?;Bell;Cell Mol. Life Sci.,2013

3. IGF2BP3 From Physiology to Cancer: Novel Discoveries, Unsolved Issues, and Future Perspectives;Mancarella;Front. Cell Dev. Biol.,2020

4. KOC (K homology domain containing protein overexpressed in cancer): A novel molecular marker that distinguishes between benign and malignant lesions of the pancreas;Yantiss;Am. J. Surg. Pathol.,2005

5. Insulin growth factor-2 binding protein 3 (IGF2BP3) is a glioblastoma-specific marker that activates phosphatidylinositol 3-kinase/mitogen-activated protein kinase (PI3K/MAPK) pathways by modulating IGF-2;Suvasini;J. Biol. Chem.,2011

Cited by 1 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Targeting Asparagine Metabolism in Well-Differentiated/Dedifferentiated Liposarcoma;Cancers;2024-08-30