OncoTargets and Therapy (Feb 2016)
Expression profile analysis of long noncoding RNA in HER-2-enriched subtype breast cancer by next-generation sequencing and bioinformatics
Abstract
Fan Yang, Shixu Lyu, Siyang Dong, Yehuan Liu, Xiaohua Zhang, Ouchen Wang Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China Background: Human epidermal growth factor receptor 2 (HER-2)-enriched subtype breast cancer is associated with a more aggressive phenotype and shorter survival time. Long noncoding RNAs (LncRNAs) have essential roles in tumorigenesis and occupy a central place in cancer progression. Notably, few studies have focused on the dysregulation of LncRNAs in the HER-2-enriched subtype breast cancer. In this study, we analyzed the expression profile of LncRNAs and mRNAs in this particular subtype of breast cancer. Methods: Seven pairs of HER-2-enriched subtype breast cancer and normal tissue were sequenced. We screened out differently expressed genes and measured the correlation of the expression levels of dysregulated LncRNAs and HER-2 by Pearson’s correlation coefficient analysis. Gene ontology analysis and pathway analysis were used to understand the biological roles of these differently expressed genes. Pathway act network and coexpression network were constructed. Results: More than 1,300 LncRNAs and 2,800 mRNAs, which were significantly differently expressed, were identified. Among these LncRNAs, AFAP1-AS1 was the most dysregulated LncRNA, while ORM2 was the most dysregulated mRNA. LOC100288637 had the highest positive correlation coefficient of 0.93 with HER-2, while RPL13P5 had the highest negative correlation coefficient of -0.87. The pathway act network showed that MAPK signaling pathway, PI3K-Akt signaling pathway, metabolic pathways, cell cycle, and regulation of actin cytoskeleton were highly related with HER-2-enriched subtype breast cancer. Coexpression network recognized LINC00636, LINC01405, ADARB2-AS1, ST8SIA6-AS1, LINC00511, and DPP10-AS1 as core genes. Conclusion: These results analyze the functions of LncRNAs and provide useful information for exploring candidate therapeutic targets and new molecular biomarkers for HER-2-enriched subtype breast cancer. Keywords: ncRNA, breast cancer, gene ontology, pathway analysis, coexpression network
