Gene Shows New Prognostic Marker For Pediatric Cancer Patients

Main Category: Cancer / Oncology
Also Included In: Pediatrics / Children's Health
Article Date: 27 Aug 2009 - 0:00 PDT

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Researchers with the National Cancer Institute have found that pediatric cancers express cancer-specific microRNAs, which may become important in understanding the biological functions of these microRNAs.

"Our microRNA profiles showed differentially expressed microRNA signatures specific to the cancer types and can be used as diagnostic and prognostic biomarkers," said Jun S. Wei, Ph.D., staff scientist in the Oncogenomics Section of the Pediatric Oncology Branch at the NCI.

Results of this study are published in Clinical Cancer Research , a journal of the American Association for Cancer Research.

Wei along with Javed Khan, M.D., senior principal investigator and chief of the Oncogenomics Section, and colleagues examined the expression of microRNAs as biomarkers for pediatric cancers. They sought to reveal the biology of these microRNAs in cancer and to examine how, or if, the transcripts of microRNA host gene affect the expression.

The researchers used microarrays to perform parallel expression profiling of microRNA and mRNA on 57 different pediatric cancer samples, representing ten different pediatric solid tumors.

Significant findings showed that 14 microRNAs were differently expressed between two of the largest sample groups in this study, neuroblastoma and rhabdomyosarcoma; eight were validated in independent human tumor samples, according to the study. More than 60 percent of microRNAs were co-regulated with their host gene transcripts - 43 of 68 microRNAs located inside known coding genes were significantly correlated.

"Among these host genes, high expression of MIRHG1, the host gene of OncomiR-1 (a known target of MYCN that is a commonly amplified gene in neuroblastoma), was significantly associated with aggressive neuroblastoma," said Wei. "Our finding implicates the adverse role of the OncomiR-1 in the biology of high-risk neuroblastoma and potential use of the expression of MIRHG1 gene as a new prognostic marker for neuroblastoma patients."

MicroRNAs have been reported to directly regulate normal cellular functions, including cell differentiation during development and pathogenesis in human cancers. While the researchers were not surprised to observe different pediatric cancer types expressing cancer-specific microRNAs, they were surprised to see the expression level of the MIRHG1 gene predicts the outcome of neuroblastoma patients independently from MYCN expression.

Future studies are needed to validate the predictive value of the MIRHG1 gene in a larger patient cohort before it can be used clinically as a prognostic factor. If validated, Wei said the expression of MIRHG1 may be used as a molecular marker to further stratify patients with high-risk neuroblastoma who do not have MYCN amplification where there currently is no marker available to predict the patient outcome in this group.

"It may be possible to specifically target OncomiR-1 as a potential novel therapy in high-risk neuroblastoma and the molecular mechanisms for the adverse effects of OncomiR-1 will need to be investigated to increase our understating of this devastating disease," he said.

Source
The American Association for Cancer Research

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