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Identification and validation of a five-lncRNA signature for predicting survival with targeted drug candidates in ovarian cancer

Nuan Lin, Jia‐zhe Lin, Yoshiaki Tanaka, Pingnan Sun, Xiaoling Zhou

2021Bioengineered33 citationsDOIOpen Access PDF

Abstract

The dysregulation of long non-coding RNAs (lncRNAs) plays a crucial role in ovarian cancer (OC). In this study, we screened out five differentially expressed lncRNAs (AC092718.4, AC138035.1, BMPR1B-DT, RNF157-AS1, and TPT1-AS1) between OC and normal ovarian based on TCGA and GTEx RNA-seq databases by using Kaplan–Meier analysis and univariate Cox, LASSO, and multivariate Cox regression. Then, a risk signature was constructed, with 1, 3, 5-year survival prediction accuracy confirmed by ROC curves, and an online survival calculator for easier clinical use. With lncRNA-microRNA-mRNA regulatory networks established, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed, suggesting the involvement of a variety of cancer-related functions and pathways. Finally, five candidate small-molecule drugs (thioridazine, trifluoperazine, loperamide, LY294002, and puromycin) were predicted by Connectivity Map. In conclusion, we identified a 5-lncRNA signature of prognostic value with its ceRNA networks, and five candidate drugs against OC.

Topics & Concepts

KEGGBiologymicroRNALong non-coding RNAOvarian cancerComputational biologyProportional hazards modelSurvival analysisOncologyBioinformaticsGeneCancerInternal medicineTranscriptomeMedicineGeneticsRNAGene expressionCancer-related molecular mechanisms researchCircular RNAs in diseasesRNA Research and Splicing