Department of Oncology, The First Affiliated Hospital of Guangdong, Pharmaceutical University, Guangzhou, China.
Department of Radiation Oncology, Affiliated Dongguan People's Hospital, Southern Medical University, Dongguan, China.
Sci Rep. 2023 Mar 20;13(1):4521. doi: 10.1038/s41598-023-31754-x.
This study aimed to investigate Hippo pathway-related prognostic long noncoding RNAs (lncRNAs) and their prognostic value in liver hepatocellular carcinoma (LIHC). Expression and clinical data regarding LIHC were acquired from The Cancer Genome Atlas and European Bioinformatics Institute array databases. Hippo pathway-related lncRNAs and their prognostic value were revealed, followed by molecular subtype investigations. Differences in survival, clinical characteristics, immune cell infiltration, and checkpoint expression between the subtypes were explored. LASSO regression was used to determine the most valuable prognostic lncRNAs, followed by the establishment of a prognostic model. Survival and differential expression analyses were conducted between two groups (high- and low-risk). A total of 313 Hippo pathway-related lncRNAs were identified from LIHC, of which 88 were associated with prognosis, and two molecular subtypes were identified based on their expression patterns. These two subtypes showed significant differences in overall survival, pathological stage and grade, vascular invasion, infiltration abundance of seven immune cells, and expression of several checkpoints, such as CTLA-4 and PD-1/L1 (P < 0.05). LASSO regression identified the six most valuable independent prognostic lncRNAs for establishing a prognosis risk model. Risk scores calculated by the risk model assigned patients into two risk groups with an AUC of 0.913 and 0.731, respectively, indicating that the high-risk group had poor survival. The risk score had an independent prognostic value with an HR of 2.198. In total, 3007 genes were dysregulated between the two risk groups, and the expression of most genes was elevated in the high-risk group, involving the cell cycle and pathways in cancers. Hippo pathway-related lncRNAs could stratify patients for personalized treatment and predict the prognosis of patients with LIHC.
本研究旨在探讨 Hippo 通路相关预后长链非编码 RNA(lncRNA)及其在肝细胞癌(LIHC)中的预后价值。从癌症基因组图谱和欧洲生物信息学研究所数组数据库中获取了与 LIHC 相关的表达和临床数据。揭示了 Hippo 通路相关 lncRNA 及其预后价值,随后进行了分子亚型研究。探讨了不同亚型之间的生存差异、临床特征、免疫细胞浸润和检查点表达。使用 LASSO 回归确定最有价值的预后 lncRNA,然后建立预后模型。在两组(高风险和低风险)之间进行生存和差异表达分析。从 LIHC 中鉴定出 313 个 Hippo 通路相关 lncRNA,其中 88 个与预后相关,并根据表达模式确定了两个分子亚型。这两个亚型在总生存率、病理分期和分级、血管浸润、七种免疫细胞浸润丰度以及 CTLA-4 和 PD-1/L1 等几个检查点的表达方面存在显著差异(P<0.05)。LASSO 回归确定了用于建立预后风险模型的六个最有价值的独立预后 lncRNA。风险模型计算的风险评分将患者分为两个风险组,AUC 分别为 0.913 和 0.731,表明高风险组生存率较差。风险评分具有独立的预后价值,HR 为 2.198。在两组之间共检测到 3007 个基因失调,大多数基因在高风险组中的表达上调,涉及细胞周期和癌症途径。Hippo 通路相关 lncRNA 可对患者进行分层以进行个性化治疗,并预测 LIHC 患者的预后。