Abstract 978: Integrated analysis of long noncoding RNA and mRNA expression profile in laryngeal squamous cell carcinoma
Authors: Wang Ru , Fang Jugao , Feng Ling 
Published: July 2016

Objective: The purpose of this study is to investigate the aberrant expressed lncRNA and mRNA in laryngeal squamous cell carcinoma (LSCC), and identify the potential lncRNA correlated with functional mRNA in LSCC.

Methods: A total number of 9 pairs of primary Stage IV LSCC and adjacent non-neoplastic tissues were surgically removed for integrated microarray analysis of lncRNA and mRNA using the Aglient GeneChip with 46506 lncRNA probes and 30656 mRNA probes. Random Variance Model(RVM) t-test was applied to filter the differentially expressed genes. Hierarchical clustering analysis was used to reveal the expression patterns of lncRNA and mRNA. GO analysis was applied to analyze the main function of the differentially expressed genes according to the Gene Ontology. Pathway analysis was used to find out the significant pathway of the differentially expressed genes according to KEGG, BioCarta and Reactome. Gene-gene interaction network was constructed based on the data of differentially expressed genes to build and analyze molecular networks. LncRNA-mRNA-network was built according to the normalized signal intensity of specific expression in mRNA and lncRNA to identify the interactions between mRNA and lncRNA. Then the significantly altered lncRNA and its correlated mRNA were validated by the qRT-PCR in an independent cohort of 30 pairs of LSCC tumor tissue and adjacent normal tissue samples.

Results: The integrated microarray analysis of lncRNA and mRNA identified 1459 differentially expressed lncRNAs and 2381 differentially expressed mRNAs, including 846 up-regulated lncRNAs and 613 down-regulated lncRNAs, 1542 up-regulated mRNAs and 839 down-regulated mRNAs(fold change≥2, p&lt;0.05). To identify typical mRNA with core functions from the identified mRNAs, the GO, KEGG pathway analysis and Gene-gene interaction network selected three mRNAs HIF1A, ITGB1, and DDIT4, which mainly involved in biological processes, such as pathways in cancer, HIF-1 signaling pathway, Focal adhesion, ECM-receptor interaction, and PI3K-Akt signaling pathway. QRT-PCR validated that the three mRNAs exhibited higher expression in cancer tissues. According to lncRNA-mRNA-network,we found that lncRNA MIR31HG was positive correlated with HIF1A, lncRNA NR-027340 was positive correlated with ITGB1, lncRNA SOX2-OT-015 was positive correlated with DDIT4. QRT-PCR further validated that the 3 lncRNAs were overexpressed in cancer tissues compared to adjacent non-neoplastic tissues of the 30 samples.

Conclusions: lncRNA MIR31HG, NR-027340, SOX2-OT-015 and their correlated mRNAs were identified in LSCC tissues by microarrays, and further validated by qRT-PCR. These up-regulated lncRNAs may act as novel biomarkers in LSCC and may be potential therapeutic targets for LSCC patients.

Citation Format: Ru Wang, Jugao Fang, Ling Feng. Integrated analysis of long noncoding RNA and mRNA expression profile in laryngeal squamous cell carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 978.