Poster Presentation Advances in Neuroblastoma Research Congress 2016

Co-expression network analysis reveals long non-coding RNA SNHG1 as a novel biomarker in neuroblastoma (#269)

Divya Sahu 1 2 3 , Chia-Lang Hsu 4 , Chen-Ching Lin 2 , Shinn-Ying Ho 3 5 , Hsueh-Fen Juan 6 7 8 , Hsuan-Cheng Huang 2
  1. Institute of Information Science, Academia Sinica, Taipei, Taiwan
  2. Institute of Biomedical Informatics, Center for Systems and Synthetic Biology, National Yang Ming University, Taipei, Taiwan
  3. Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan
  4. Institute of Molecular and Cellular Biology, National Taiwan University, Taipei, Taiwan
  5. Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan
  6. Institute of Molecular and Cellular Biology, National Taiwan University, Taipei, Taiwan
  7. Department of Life Science, National Taiwan University, Taipei, Taiwan
  8. Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan

Background:

Currently, several long non-coding RNAs (lncRNAs) observed to be aberrantly expressed in cancer and modulate the fundamental biological processes. However, few of them have been established as prognostic biomarker. Here, we aim to find differentially expressed lncRNAs and its co-expressed coding genes regulated by N-Myc in the MYCN amplified neuroblastoma.

Methods:

Publicly available microarray expression profile was analyzed to identify differentially expressed transcripts in the MYCN amplified compared to MYCN non-amplified condition. Biological functions of the differential coding genes were identified by ClueGO. Association between lncRNA and coding gene was determined through Spearman correlation coefficient (SCC) and Fischer’s Z transformation. MYCN Chip-Seq data set was used to find binding sites of MYCN in the promoter of the regulated genes. Relative expression of common lncRNAs identified in microarray and RNA-Seq differential expression study were validated by RT-qPCR. Moreover, survival analysis and cox regression analysis was performed in the neuroblastoma cohort (n= 493).

Results:

We found 591 coding genes and 13 lncRNAs to be differentially expressed (fold change >= 2 and p <= 0.05). Functional enrichment analysis reveals cell cycle progression for the up-regulated genes and neuron development, synapse assembly for the down-regulated genes. The co-expression data with a z-score threshold ≥ 3.0 and further a SCC cut off >= 0.8, filtered 39 co-expressed pairs. Among which, SNHG1 and TAF1D were found to be highly correlated. Next, patients with high risk neuroblastoma express significant high SNHG1 than those with low risk disease (p < 2.2E-16), and high expression of SNHG1 is critical to patient event free survival (p < 9.37E-13). Moreover, multivariate Cox regression analysis reveals hazard ratio of 1.58 (n= 493, p = 2.36E-02).

Conclusion:

SNHG1 and TAF1D are significantly correlated and regulated by N-Myc. Moreover, lncRNA SNHG1 might serve as a novel biomarker for high risk neuroblastoma intervention.

 

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