Zhang La, Zhang Xiuzhen, Zhao Wei, Xiao Xinyu, Liu Shanshan, Peng Qiling, Jiang Ning, Zhou Baoyong
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
School of Basic Medical Science, Chongqing Medical University, Chongqing, China.
Front Med (Lausanne). 2022 Mar 2;9:760722. doi: 10.3389/fmed.2022.760722. eCollection 2022.
Pyroptosis, a novel pro-inflammatory type of programmed cell death, is involved in the tumorigenesis of various cancers. Recent findings have implicated long non-coding RNAs (lncRNAs) in the serial steps of cancer development. However, the expression and prognostic signatures of pyroptosis-related lncRNAs in hepatocellular carcinoma (HCC) remain largely unknown. Therefore, a pyroptosis-related lncRNA prognostic model was constructed for HCC. Thirty-four pyroptosis-related genes were obtained from previous reviews, and gene expression data were collected from The Cancer Genome Atlas (TCGA) database. Spearman's correlation test was used to identify potential pyroptosis-related lncRNAs. Cox and LASSO regression analyses were used to construct a prognostic model. Subsequently, receiver operating characteristic (ROC) curves were constructed to assess the model's predictive ability for the overall survival (OS) of HCC patients. CytoHubba was used to screen out the potential hub gene, whose expression was verified using clinical samples from HCC patients. Finally, nine pyroptosis-related differentially expressed lncRNAs in HCC were identified, and a prognostic model with four pyroptosis-related lncRNAs was constructed with an area under the ROC curve (AUC) of approximately 0.734. Single-sample gene set enrichment analysis and TCGA revealed different immune infiltration and immune checkpoints between the two risk groups. Moreover, these lncRNAs are closely related to the pyroptosis-related gene, NLRP6, which may be considered a hub gene. NLRP6 was lower-expressed in HCC samples, and patients with lower expression of NLRP6 had the longer OS. In conclusion, NLRP6-dependent pyroptosis-related lncRNAs play important roles in tumor immunity and may be potential predictors and therapeutic targets for HCC.
细胞焦亡是一种新型的促炎性程序性细胞死亡，参与多种癌症的肿瘤发生。最近的研究结果表明，长链非编码RNA（lncRNA）在癌症发展的一系列步骤中发挥作用。然而，肝细胞癌（HCC）中细胞焦亡相关lncRNA的表达和预后特征在很大程度上仍不清楚。因此，构建了一个用于HCC的细胞焦亡相关lncRNA预后模型。从以往的综述中获取了34个细胞焦亡相关基因，并从癌症基因组图谱（TCGA）数据库收集了基因表达数据。使用Spearman相关性检验来鉴定潜在的细胞焦亡相关lncRNA。采用Cox和LASSO回归分析构建预后模型。随后，构建受试者工作特征（ROC）曲线以评估该模型对HCC患者总生存期（OS）的预测能力。使用CytoHubba筛选出潜在的枢纽基因，并通过HCC患者的临床样本验证其表达。最终，在HCC中鉴定出9个细胞焦亡相关差异表达的lncRNA，并构建了一个包含4个细胞焦亡相关lncRNA的预后模型，其ROC曲线下面积（AUC）约为0.734。单样本基因集富集分析和TCGA显示，两个风险组之间存在不同的免疫浸润和免疫检查点。此外，这些lncRNA与细胞焦亡相关基因NLRP6密切相关，NLRP6可能被视为枢纽基因。NLRP6在HCC样本中表达较低，NLRP6表达较低的患者OS较长。总之，NLRP6依赖性细胞焦亡相关lncRNA在肿瘤免疫中发挥重要作用，可能是HCC的潜在预测指标和治疗靶点。
