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// Divya Sahu 1, 2, 3 , Chia-Lang Hsu 4 , Chen-Ching Lin 3 , Tz-Wen Yang 5 , Wen-Ming Hsu 6 , Shinn-Ying Ho 1, 2, 7 , Hsueh-Fen Juan 4, 5, 8 , Hsuan-Cheng Huang 2, 3 1 Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan 2 Bioinformatics Program, Taiwan International Graduate Program, Institute of Information Science, Academia Sinica, Taipei, Taiwan 3 Institute of Biomedical Informatics, Center for Systems and Synthetic Biology, National Yang-Ming University, Taipei, Taiwan 4 Department of Life Science, National Taiwan University, Taipei, Taiwan 5 Institute of Molecular and Cellular Biology, National Taiwan University, Taipei, Taiwan 6 Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan 7 Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan 8 Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan Correspondence to: Hsueh-Fen Juan, email: yukijuan@ntu.edu.tw Hsuan-Cheng Huang, email: hsuancheng@ym.edu.tw Keywords: neuroblastoma, long noncoding RNAs, SNHG1, co-expression study, event-free survival Received: April 24, 2016 Accepted: July 28, 2016 Published: August 09, 2016 ABSTRACT Despite of the discovery of protein therapeutic targets and advancement in multimodal therapy, the survival chance of high-risk neuroblastoma (NB) patients is still less than 50%. MYCN amplification is a potent driver of NB, which exerts its oncogenic activity through either activating or inhibiting the transcription of target genes. Recently, long noncoding RNAs (lncRNAs) are reported to be altered in cancers including NB. However, lncRNAs that are altered by MYCN amplification and associated with outcome in high-risk NB patients are limitedly discovered. Herein, we examined the expression profiles of lncRNAs and protein-coding genes between MYCN amplified and MYCN non-amplified NB from microarray ( n = 47) and RNA-seq datasets ( n = 493). We identified 6 lncRNAs in common that were differentially expressed (adjusted P ≤ 0.05 and fold change ≥ 2) and subsequently validated by RT-qPCR. The co-expression analysis reveals lncRNA, SNHG1 and coding gene, TAF1D highly co-expressed in NB. Kaplan-Meier analysis shows that higher expression of SNHG1 is significantly associated with poor patient survival. Importantly, multivariate analysis confirms high expression of SNHG1 as an independent prognostic marker for event-free survival (EFS) (HR = 1.58, P = 2.36E-02). In conclusion, our study unveils that SNHG1 is up-regulated by MYCN amplification and could be a potential prognostic biomarker for high-risk NB intervention. |
