Oncotarget

Research Papers:

Co-expression analysis identifies long noncoding RNA SNHG1 as a novel predictor for event-free survival in neuroblastoma

Divya Sahu, Chia-Lang Hsu, Chen-Ching Lin, Tz-Wen Yang, Wen-Ming Hsu, Shinn-Ying Ho, Hsueh-Fen Juan and Hsuan-Cheng Huang _

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Oncotarget. 2016; 7:58022-58037. https://doi.org/10.18632/oncotarget.11158

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Abstract

Divya Sahu1,2,3, Chia-Lang Hsu4, Chen-Ching Lin3, Tz-Wen Yang5, Wen-Ming Hsu6, Shinn-Ying Ho1,2,7, Hsueh-Fen Juan4,5,8, Hsuan-Cheng Huang2,3

1Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan

2Bioinformatics Program, Taiwan International Graduate Program, Institute of Information Science, Academia Sinica, Taipei, Taiwan

3Institute of Biomedical Informatics, Center for Systems and Synthetic Biology, National Yang-Ming University, Taipei, Taiwan

4Department of Life Science, National Taiwan University, Taipei, Taiwan

5Institute of Molecular and Cellular Biology, National Taiwan University, Taipei, Taiwan

6Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan

7Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan

8Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan

Correspondence to:

Hsueh-Fen Juan, email: [email protected]

Hsuan-Cheng Huang, email: [email protected]

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.


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