Comparison of dysregulated long noncoding RNAs in lung adenocarcinoma and spinal metastasis: A genome-wide analysis.

Houlei Wang, Shengxing Wang, Peng Liu, Yiqun Ma, Annan Hu, Chi Sun,  Jian Dong

Abstract:

Long noncoding RNAs (lncRNAs) have been shown to play crucial roles in cancer metastasis, yet the lncRNAs landscape of lung adenocarcinoma has not been completely characterized. The aim of this study was to assess the expression profile and potential function of lncRNA in lung adenocarcinoma and in spinal metastasis (SM). A genome-wide microarray analysis was conducted on lung adenocarcinoma and SM tissue from ten Chinese patients. A total of 3,345 differentially expressed lncRNAs were detected. Of those, 761 lncRNAs were upregulated and 2,584 were downregulated (fold-change >2.0, p<0.05). These differentially expressed lncRNAs were not evenly distributed among the chromosomes of human genome. Volcano plots of these differentially expressed lncRNAs revealed large variability in lncRNAs expression among 12 patients, indicating that certain lncRNAs may play a positive role in SM of lung adenocarcinoma. Gene Ontology enrichment and pathway analysis identified several remarkably dysregulated biological pathways that affect cell adhesion and the interaction of cytokines and cytokine receptors. Co-expression network analysis showed that 9,458 lncRNAs had verified cis- and trans- target genes. All 2,317 cis targeted genes were confirmed to be differentially expressed and influenced by dysregulated lncRNAs in SM of lung adenocarcinoma. Top ten markedly dysregulated lncRNAs and mRNAs were verified from the co-expression network. In conclusion, this study was a genome-wide survey of dysregulated lncRNAs and corresponding mRNAs that comprise co-regulation networks for SM and lung adenocarcinoma tissues. These dysregulated lncRNAs and mRNA networks could be used as therapeutic gene targets to prevent SM of lung adenocarcinoma and to predictively evaluate treatment efficacy.