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IGF2BP1 harbors prognostic significance by gene gain and diverse expression in neuroblastoma
Jessica L Bell1, Raseswari Turlapati1, Tao Liu1
1Jessica L. Bell, Raseswari Turlapati, and Stefan Hüttelmaier, Martin Luther University Halle-Wittenberg, Halle; Johannes H. Schulte, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, and University Children's Hospital Essen, Essen; Johannes H. Schulte, German Cancer Consortium and German Cancer Research Center, Heidelberg, Germany; and Tao Liu, Children's Cancer Institute Australia for Medical Research and University of New South Wales, Randwick, New South Wales, Australia.
Purpose:
Chromosomal 17q21-ter gain in neuroblastoma is both a common and prognostically significant event. The insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1) gene is located near the proximal edge of this region. Here, its prognostic value is evaluated in neuroblastoma.
Methods:
The mRNA expression of IGF2BP family members was first evaluated by microarray data sets. In addition, in a separate cohort of 69 tumors, IGF2BP1 gene copy number, mRNA, and protein abundance were determined and compared with clinical parameters.
Results:
In two independent microarray data sets, 77% to 100% of tumors had substantial IGF2BP1 mRNA levels measured. High IGF2BP1 transcript abundance was significantly associated with stage 4 tumors (P < .001) and decreased patient survival (P < .001). IGF2BP1 was also associated with MYCN gene amplification and MYCN mRNA abundance. In the 69 neuroblastoma samples, IGF2BP1 DNA copy number (increased in 84% of tumors), mRNA, and protein abundance were significantly higher in stage 4 compared with stage 1 tumors. Importantly, IGF2BP1 protein levels were associated with lower overall patient survival (P = .012) and positively correlated with MYCN mRNA, even when excluding MYCN-amplified tumors. Moreover, IGF2BP1 clearly affected MYCN expression and neuroblastoma cell survival in vitro.
Conclusion:
In neuroblastoma, IGF2BP1 was expressed in the majority of neuroblastoma specimens analyzed and was associated with lower overall patient survival and MYCN abundance. These data demonstrate that IGF2BP1 is a potential oncogene and an independent negative prognostic factor in neuroblastoma.
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