Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
World J Gastroenterol. 2019 Jan 14;25(2):220-232. doi: 10.3748/wjg.v25.i2.220.
Recent evidence shows that long non-coding RNAs (lncRNAs) are closely related to hepatogenesis and a few aggressive features of hepatocellular carcinoma (HCC). Increasing studies demonstrate that lncRNAs are potential prognostic factors for HCC. Moreover, several studies reported the combination of lncRNAs for predicting the overall survival (OS) of HCC, but the results varied. Thus, more effort including more accurate statistical approaches is needed for exploring the prognostic value of lncRNAs in HCC.
To develop a robust lncRNA signature associated with HCC recurrence to improve prognosis prediction of HCC.
Univariate COX regression analysis was performed to screen the lncRNAs significantly associated with recurrence-free survival (RFS) of HCC in GSE76427 for the least absolute shrinkage and selection operator (LASSO) modelling. The established lncRNA signature was validated and developed in The Cancer Genome Atlas (TCGA) series using Kaplan-Meier curves. The expression values of the identified lncRNAs were compared between the tumor and non-tumor tissues. Pathway enrichment of these lncRNAs was conducted based on the significantly co-expressed genes. A prognostic nomogram combining the lncRNA signature and clinical characteristics was constructed.
The lncRNA signature consisted of six lncRNAs: , , , , , and . This risk model was significantly associated with the RFS of HCC in the TCGA cohort with a hazard ratio (HR) being 1.807 (95%CI [confidence interval]: 1.329-2.457) and log-rank -value being less than 0.001. The best candidates of the six-lncRNA signature were younger male patients with HBV infection in relatively early tumor-stage and better physical condition but with higher preoperative alpha-fetoprotein. All the lncRNAs were significantly upregulated in tumor samples compared to non-tumor samples ( < 0.05). The most significantly enriched pathways of the lncRNAs were TGF-β signaling pathway, cellular apoptosis-associated pathways, . The nomogram showed great utility of the lncRNA signature in HCC recurrence risk stratification.
We have constructed a six-lncRNA signature for prognosis prediction of HCC. This risk model provides new clinical evidence for the accurate diagnosis and targeted treatment of HCC.
最近的证据表明，长链非编码 RNA（lncRNAs）与肝发生和肝细胞癌（HCC）的一些侵袭性特征密切相关。越来越多的研究表明，lncRNAs 是 HCC 的潜在预后因素。此外，一些研究报告了 lncRNAs 联合用于预测 HCC 的总生存期（OS），但结果存在差异。因此，需要包括更准确的统计方法在内的更多努力来探索 lncRNAs 在 HCC 中的预后价值。
构建与 HCC 复发相关的稳健 lncRNA 特征，以改善 HCC 预后预测。
使用最小绝对收缩和选择算子（LASSO）模型对 GSE76427 中与 HCC 无复发生存（RFS）显著相关的 lncRNAs 进行单因素 COX 回归分析。使用 Kaplan-Meier 曲线在 The Cancer Genome Atlas（TCGA）系列中验证和开发建立的 lncRNA 特征。比较肿瘤和非肿瘤组织中鉴定的 lncRNAs 的表达值。根据显著共表达基因对这些 lncRNAs 进行通路富集分析。构建包含 lncRNA 特征和临床特征的预后列线图。
该 lncRNA 特征由六个 lncRNAs 组成：、、、、、。该风险模型与 TCGA 队列中 HCC 的 RFS 显著相关，风险比（HR）为 1.807（95%CI [置信区间]：1.329-2.457），对数秩检验值小于 0.001。六个 lncRNA 特征的最佳候选者是年龄较小的男性 HBV 感染患者，肿瘤分期相对较早，身体状况较好，但术前甲胎蛋白较高。与非肿瘤样本相比，所有 lncRNAs 在肿瘤样本中均显著上调（<0.05）。lncRNAs 最显著富集的途径是 TGF-β 信号通路、细胞凋亡相关途径、。列线图显示 lncRNA 特征在 HCC 复发风险分层中有很好的应用。
我们构建了一个用于预测 HCC 预后的六 lncRNA 特征。该风险模型为 HCC 的准确诊断和靶向治疗提供了新的临床证据。
