Expression And Bioinformatics Of Long Non-Coding RNA In Epithelial Ovarian Cancer

Objective: to establish the differential expression profiles of lnc RNA and mRNA in epithelial ovarian cancer tissues and normal ovarian tissues by microarray,and bioinformatics analysis of differentially expressed genes.Methods: Total RNAs were extracted from EOC and normal ovarian tissue,expression level of genome-wide scale lncRNA was determined by microarray.Data analyses were performed using GeneSpring software V13.0and R.Realtime fluorescence quantitative PCR method was used to verify the results of microarray experiments.In order to predict the function of lncRNAs which corresponding to the differential expression probe,the expression of mRNA co-expressed with lncRNA was analyzed.Firstly,we investigated the expression of mRNA in tumor tissues and normal tissues.Then,the potential function of lncRNA was speculated by analyzing the function of mRNA.First,from the point of view of biological function,the mRNA was analyzed by GO enrichment;second,KEGG enrichment was analyzed from the aspect of pathway;third,By calculating the Pearson correlation coefficient of lncRNA and mRNA to explore the correlation between them.We performed 2D cluster analysis of the lncRNA and mRNA expression data of all tumor samples in thesubgroup.Finally,we compared our results with those obtained from other ovarian cancer studies in GEO database by comparing the expression of lncRNA and mRNA.Results: A total of 741 up and 3440 down regulated probes were identified to be significantly and differentially expressed in EOC.We use Real-time PCR to verified our results,the above results are consistent with gene chip measured results.The annotation result of their co-expressed mRNAs showed that the most significantly related category was tumor immunity and Cell adhesion,and the most significantly related pathway was Cell adhesion molecules.Through building the network of differentially expressed lncRNA which regulated by upstream transcription factors,we found that the differential expression of lncRNAs is mainly regulated by Oct1,pax4,Nkx2-5,FOXD3 and HNF-1.Subgroup analysis showed that the expression of lncRNA and mRNA in EOC tissue samples were divided into two groups,combined with clinical datas,the two groups were identified as drug resistant group and non drug resistant group,42 lncRNA probe and 49 mRNA probes were specifically differentially expressed between them.GO analysis revealed that differential of mRNA is mainly enriched in the cell cycle and biological process of adhesion,While KEGG analysis showed that differential of mRNA related to cell growth and death.Our results consistent with ovarian cancer datas in the GEO database analyzed by overlapping analyzed.Conclusion: Our study indicated that clusters of lncRNAs were significantly and differentially expressed in EOC compared with normal ovarian cancer tissues in the same subject,the difference is closely related to the occurrence of tumor and the drug resistance.