The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Nanjing, Jiangsu, China.
Research Center for Clinical Oncology, Jiangsu Cancer Hospital, Nanjing, Jiangsu, China.
Cancer Med. 2019 Mar;8(3):863-873. doi: 10.1002/cam4.1813. Epub 2019 Feb 4.
Long noncoding RNAs (lncRNAs) are aberrantly expressed in various cancers types and can function as competing endogenous RNAs (ceRNAs), which promote and maintain tumor initiation and progression. In this study, we explored the functional roles and regulatory mechanisms of lncRNAs as ceRNAs in colorectal cancer and their clinical potential as biomarkers. The RNA sequencing profiles of patients with colorectal cancer were downloaded from TCGA database, and 62 lncRNAs, 30miRNAs, and 59 mRNAs were identified to comprise the ceRNA network (fold change > 2, P < 0.01). Functional enrichment analysis suggested that the target genes of the ceRNA network may be involved in the pathways related to cancer, including the signaling pathway that regulates the pluripotency of stem cells, wnt signaling pathway, hippo signaling pathway, basal cell carcinoma, and colorectal cancer. Univariate and multivariate Cox's proportional hazard regression model revealed that five (H19, MIR31HG, HOTAIR, WT1-AS, and LINC00488) out of 62 lncRNAs were closely related to the overall survival (OS) (P < 0.05). Furthermore, the five-lncRNA model could be an independent prognostic model in colorectal cancer. We computed for the risk function and constructed a risk score based on the five lncRNAs. Results showed that patients with high-risk scores have poor survival rates. Additionally, combing the risk score and other clinicopathological features, we can better predict the patient's survival probabilities. Furthermore, we validate our model in the GSE38832 dataset. Collectively, our study has provided a deeper understanding of the lncRNA-related ceRNA regulatory mechanism in CRC and identified five-lncRNA model, which could be considered as candidate prognostic biomarkers and therapeutic targets.
长链非编码 RNA（lncRNAs）在多种癌症类型中表达异常，并可作为竞争性内源性 RNA（ceRNA）发挥作用，促进和维持肿瘤的发生和发展。在本研究中，我们探讨了 lncRNA 作为 ceRNA 在结直肠癌中的功能作用和调控机制及其作为生物标志物的临床潜力。从 TCGA 数据库中下载了结直肠癌患者的 RNA 测序谱，确定了 62 个 lncRNA、30 个 miRNA 和 59 个 mRNA 组成 ceRNA 网络（fold change > 2，P < 0.01）。功能富集分析表明，ceRNA 网络的靶基因可能参与与癌症相关的途径，包括调节干细胞多能性的信号通路、Wnt 信号通路、 Hippo 信号通路、基底细胞癌和结直肠癌。单变量和多变量 Cox 比例风险回归模型显示，62 个 lncRNA 中有 5 个（H19、MIR31HG、HOTAIR、WT1-AS 和 LINC00488）与总生存期（OS）密切相关（P < 0.05）。此外，五-lncRNA 模型可作为结直肠癌的独立预后模型。我们计算了风险函数，并基于这 5 个 lncRNA 构建了风险评分。结果表明，高风险评分的患者生存率较低。此外，结合风险评分和其他临床病理特征，我们可以更好地预测患者的生存概率。此外，我们在 GSE38832 数据集上验证了我们的模型。综上所述，我们的研究深入了解了 lncRNA 相关 ceRNA 在 CRC 中的调控机制，并确定了五-lncRNA 模型，可作为候选预后生物标志物和治疗靶点。
