Guo Liyuan, Peng Yan, Meng Yuanyuan, Liu Yunduo, Yang Shangshang, Jin Hong, Li Qi
Gynecological Cancer Department, Harbin Medical University Cancer Hospital, Harbin 150081, China.
Disease Prevention Center, First Affiliated Hospital of Heilongjiang University of Chinese Traditional Medicine, Harbin 150040, China.
Oncotarget. 2017 Jul 26;8(40):68483-68492. doi: 10.18632/oncotarget.19590. eCollection 2017 Sep 15.
Emerging evidence shows that dysregulated expression of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) were closely linked with disease progression, including cancers. However, the joint predictive power of miRNAs and lncRNAs in prognosis for ovarian cancer (OV) patients with wild-type BRCA1/2 is as yet unknown. In this study, we sought to assess the joint predictive power of miRNAs and lncRNAs by integrating miRNA and lncRNA expression profiles and clinical data of 281 OV patients with wild-type BRCA1/2 from The Cancer Genome Atlas (TCGA) project. Finally, we identified an integrated miRNA-lncRNA signature composing of two lncRNAs ( and ) and two miRNAs ( and ) which can effectively classify OV patients with wild-type BRCA1/2 into groups with the good and poor outcome. The prognostic value of the integrated miRNA-lncRNA signature was validated in the testing cohort and entire TCGA cohort. Multivariate analysis demonstrated the independence of the integrated miRNA-lncRNA signature of known other clinical factors. Further analysis suggested that patients who were in the low-risk group based on the signature achieved a better CR from platinum-based chemotherapy compared with patients in the high-risk group. Our results indicated that this integrated miRNA-lncRNA signature may have important clinical implications for risk stratification of ovarian cancer patients with wild-type BRCA1/2.
新出现的证据表明,微小RNA(miRNA)和长链非编码RNA(lncRNA)的表达失调与包括癌症在内的疾病进展密切相关。然而,miRNA和lncRNA对野生型BRCA1/2的卵巢癌(OV)患者预后的联合预测能力尚不清楚。在本研究中,我们通过整合来自癌症基因组图谱(TCGA)项目的281例野生型BRCA1/2的OV患者的miRNA和lncRNA表达谱及临床数据,来评估miRNA和lncRNA的联合预测能力。最后,我们鉴定出一个由两个lncRNA( 和 )和两个miRNA( 和 )组成的整合miRNA-lncRNA特征,其可有效地将野生型BRCA1/2的OV患者分为预后良好和不良的组。该整合miRNA-lncRNA特征的预后价值在测试队列和整个TCGA队列中得到验证。多变量分析证明了该整合miRNA-lncRNA特征独立于其他已知临床因素。进一步分析表明,基于该特征处于低风险组的患者与高风险组患者相比,从铂类化疗中获得了更好的完全缓解。我们的结果表明,这种整合miRNA-lncRNA特征可能对野生型BRCA1/2的卵巢癌患者的风险分层具有重要的临床意义。