Department of Bioinformatics, The Basic Medical School of Chongqing Medical University, Chongqing 400016, P.R. China.
Molecular and Tumor Research Center, Chongqing Medical University, Chongqing 400016, P.R. China.
Int J Oncol. 2018 Aug;53(2):866-876. doi: 10.3892/ijo.2018.4403. Epub 2018 May 11.
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.
为了研究长链非编码 RNA（lncRNA）在预测高级别浆液性卵巢癌（HGS-OvCa）患者对铂类化疗耐药中的作用，通过分析来自在线数据库的 561 个微阵列和 136 个 RNA 测序（RNA-seq）标本，开发了一个 7-lncRNA 特征[优势比（OR），2.859；P<0.0001]。上调的 lncRNA（RP11-126K1.6、ZBED3-AS1、RP11-439E19.10 和 RP11-348N5.7）和下调的 lncRNA[RNF144A-AS1、生长停滞特异 5（GAS5）和 F11-AS1]在预测基因表达组和癌症基因组图谱中的化疗耐药性方面具有较高的敏感性和特异性（曲线下面积>0.8）。lncRNA 特征独立于临床特征和 4 种 HGS-OvCa 分子亚型。该特征与无病生存期呈负相关（n=47；对数秩，P<0.01）。此外，7 个 lncRNA 的表达与微阵列（GSE63885、GSE51373、GSE15372 和 GSE9891）和 RNA-seq 数据一致。在体外实验中，ZBED3-AS1、F11-AS1 和 GAS5 在已知对铂类药物耐药和非耐药的细胞系中表达差异，这与本研究结果一致。该 lncRNA 特征可作为预测 HGS-OvCa 对铂类化疗耐药的预后标志物。这些发现可能有助于未来为 HGS-OvCa 患者制定个体化治疗方案。
