A panel of 7 prognosis-related long non-coding RNAs to improve platinum-based chemoresistance prediction in ovarian cancer

Abstract

In order to study the role of long non-coding RNAs (lncRNAs) in predicting platinum-based chemoresistance in patients with high-grade serous ovarian carcinoma (HGS-OvCa), a=7-lncRNA signature was developed by analyzing 561 microarrays and 136 specimens from RNA-sequencing (RNA-seq) obtained from online databases [odds ratio (OR), 2.859; P<0.0001]. The upregulated lncRNAs (RP11-126K1.6, ZBED3-AS1, RP11-439E19.10 and RP11-348N5.7) and downregulated lncRNAs [RNF144A-AS1, growth arrest specific 5 (GAS5) and F11-AS1] exhibited high sensitivity and specificity in predicting chemoresistance in the Gene Expression Omnibus and the Cancer Genome Atlas (area under curve >0.8). The lncRNA signature was independent of clinical characteristics and 4 HGS-OvCa molecular subtypes. This signature was negatively associated with disease-free survival (n=47; log-rank, P<0.01). Furthermore, the expression of the 7 lncRNAs was consistent with microarray (GSE63885, GSE51373, GSE15372 and GSE9891) and RNA-seq data. In in vitro experiments, ZBED3-AS1, F11-AS1 and GAS5 were differentially expressed in cell lines that are known to be resistant and non-resistant to platinum-based drugs, which was consistent with the results in the present study. This lncRNA signature may be used as a prognostic marker for predicting resistance to platinum-based chemotherapeutics in HGS-OvCa. These findings may contribute to individualized therapies in patients with HGS-OvCa in the future.