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The Role of IMP3 Expression in Patients With Neuroblastoma

2014-08-27 03:13:46 | BioPortfolio

Summary

Neuroblastoma (NB), a common cancer of early childhood originating from primitive sympathetic neural precursors, is characterized by the remarkable heterogeneity of clinical behaviors from spontaneous regression to rapid progression and death. The current therapeutic options are developed according to the Children's Oncology Group (COG) risk stratification criteria based on clinical and biological factors, including tumor stage, MYCN status, age at diagnosis, histology, and ploidy status. 1-2 The treatment strategies ranging from observation alone to intensive multimodality therapy depends on the risk stratification of three subgroups of low, intermediate, and high risk of death. Despite a number of molecular and biologic factors has been identified to predict the prognosis, MYCN amplification, which occurring in roughly 20% of primary NB, is one of the most powerful prognostic factors.3 The co-opting neurotrophin pathways including the neurotrophin receptors (TrkA, TrkB, and TrkC) and their ligands (NGF, BDNF, and neurotrophin-3, respectively), which regulate the differentiation, apoptosis, and growth of neural cells, are also important molecules related to the prognosis of NB.4 However, a proportion of patients with MYCN nonamplified NB still presents clinically aggressive progression similar to those of MYCN amplified tumors, suggesting that other unfavorable molecules exist for the inferior survival.5-6 The IGF-II RNA-binding protein 3 (IMP3), also known as L532S or K homology domain-containing protein overexpressed in cancer (KOC), is a member of RNA-binding protein family which includes IMP1, IMP2, and IMP3. The IMPs are primarily expressed during early embryogenesis and have been implicated in various post-transcriptional functions, including mRNA localization, cell growth, and cell migration during early embryogenesis.7-8 The IMP3 orthologue Vg1-RBP in Xenopus has also been described to promote migration of neural crest cells.9 Recently, the IMP3 is considered an oncofetal protein by increasing proliferation and invasion in various cancers including pancreas, kidney, and lung cancers.10-14 The expression of IMP3 is, however, low or undetectable in adjacent benign tissues.13 These lines of evidence indicate that IMP3 is capable of a potential biomarker to predict cancer progression and metastasis, and may serve as a target molecule for cancer therapy.14

oligonucleotide microarray is a powerful tool to do a genome-wide screening of candidate genes related to cancer prognosis.15 In this study, 22 primary NB tumors were subjected to oligonucleotide microarray analysis. Among the differentially expressed genes according to the patients' prognosis, IMP3 showed an especially high expression level in NB tumors carrying unfavorable prognosis. Further evaluation of IMP3 expression in a large sample size demonstrated that IMP3 expression could predict an unfavorable prognosis of NB patients independent of other biomarkers. Targeting of IMP3 expression in a NB cell line did suppress cell invasion ability, suggesting that IMP3 could not only be a prognostic factor, but also be a potential therapeutic target of NB.

Study Design

Observational Model: Cohort, Time Perspective: Retrospective

Conditions

Neuroblastoma

Location

Wen-Ming Hsu
Taipei
Taiwan
100

Status

Completed

Source

National Taiwan University Hospital

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:13:46-0400

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Medical and Biotech [MESH] Definitions

An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)

A malignant olfactory neuroblastoma arising from the olfactory epithelium of the superior nasal cavity and cribriform plate. It is uncommon (3% of nasal tumors) and rarely is associated with the production of excess hormones (e.g., SIADH, Cushing Syndrome). It has a high propensity for multiple local recurrences and bony metastases. (From Holland et al., Cancer Medicine, 3rd ed, p1245; J Laryngol Otol 1998 Jul;112(7):628-33)

A moderately malignant neoplasm composed of primitive neuroectodermal cells dispersed in myxomatous or fibrous stroma intermixed with mature ganglion cells. It may undergo transformation into a neuroblastoma. It arises from the sympathetic trunk or less frequently from the adrenal medulla, cerebral cortex, and other locations. Cervical ganglioneuroblastomas may be associated with HORNER SYNDROME and the tumor may occasionally secrete vasoactive intestinal peptide, resulting in chronic diarrhea.

Genes of IAP elements (a family of retrovirus-like genetic elements) which code for virus-like particles (IAPs) found regularly in rodent early embryos. ("Intracisternal" refers to the cisternae of the endoplasmic reticulum.) Under certain circumstances, such as DNA hypomethylation they are transcribed. Their transcripts are found in a variety of neoplasms, including plasmacytomas, neuroblastoma, rhabdomyosarcomas, teratocarcinomas, and colon carcinomas.

Family of retrovirus-associated DNA sequences (ras) originally isolated from Harvey (H-ras, Ha-ras, rasH) and Kirsten (K-ras, Ki-ras, rasK) murine sarcoma viruses. Ras genes are widely conserved among animal species and sequences corresponding to both H-ras and K-ras genes have been detected in human, avian, murine, and non-vertebrate genomes. The closely related N-ras gene has been detected in human neuroblastoma and sarcoma cell lines. All genes of the family have a similar exon-intron structure and each encodes a p21 protein.

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