Xue Chen, Zhao Yalei, Jiang Jianwen, Li Lanjuan
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou 310003, China.
National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou 310003, China.
Am J Transl Res. 2020 May 15;12(5):1873-1883. eCollection 2020.
Studies have demonstrated that long non-coding RNAs (lncRNAs) play important roles in cancer development and progression. However, associations between the expression patterns and prognostic roles of lncRNAs in hepatocellular carcinoma (HCC) have not been comprehensively described. In this study, we established a prognostic model of lncRNA expression using public datasets of HCC from The Cancer Genome Atlas (TCGA) and adopted the International Cancer Genome Consortium (ICGC) as an independent cohort to validate the stability of our model. Cox regression analysis was used to explore the independent prognostic factor in both training and validation cohorts. Additionally, we explored the functional roles of lncRNAs using bioinformatic analyses. According to lncRNA consensus clusters, we resolved the distribution of molecular and clinical data and observed that individual lncRNA could function as prognostic biomarkers in HCC. Furthermore, the novel lncRNA molecular subtypes were statistically significant for predicting HCC status, which was validated by nested cross-validation. We found that lncRNA subtypes were partially related to gender, histological grade, and mutations within TP53. The lncRNA subtypes were also consistent with mRNA-based subtypes, and pathway enrichment analysis identified the involvement of multiple signaling pathways. In addition, we observed that upregulated DANCR was significantly associated with poor prognosis in HCC patients. In conclusion, our model based on lncRNA expression is statistically significant as a diagnostic and prognostic indicator for patients with HCC.
研究表明,长链非编码RNA(lncRNAs)在癌症发生和发展中发挥重要作用。然而,lncRNAs在肝细胞癌(HCC)中的表达模式与预后作用之间的关联尚未得到全面描述。在本研究中,我们利用来自癌症基因组图谱(TCGA)的HCC公共数据集建立了lncRNA表达的预后模型,并采用国际癌症基因组联盟(ICGC)作为独立队列来验证我们模型的稳定性。使用Cox回归分析在训练和验证队列中探索独立预后因素。此外,我们利用生物信息学分析探索lncRNAs的功能作用。根据lncRNA共识聚类,我们解析了分子和临床数据的分布,并观察到单个lncRNA可作为HCC的预后生物标志物。此外,新的lncRNA分子亚型对预测HCC状态具有统计学意义,这通过嵌套交叉验证得到了验证。我们发现lncRNA亚型与性别、组织学分级以及TP53内的突变部分相关。lncRNA亚型也与基于mRNA的亚型一致,并且通路富集分析确定了多个信号通路的参与。此外,我们观察到上调的DANCR与HCC患者的不良预后显著相关。总之,我们基于lncRNA表达的模型作为HCC患者的诊断和预后指标具有统计学意义。