Huang Deliang, Huang Dejing
Department of Interventional Medicine, Yellow River Central Hospital, Zhengzhou, Henan Province, China.
Department of Thoracic Surgery, The Second Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
Heliyon. 2022 Oct 7;8(10):e10931. doi: 10.1016/j.heliyon.2022.e10931. eCollection 2022 Oct.
Patients with mid-stage HCC (hepatocellular carcinoma) may benefit from transcatheter arterial chemoembolization (TACE). However, patient efficacy varies widely, and the detailed assessment index is unknown. The most general methylation alteration in mRNA (Messenger RNA), N6-methyladenosine (m6A), is controlled by the m6A regulator, which is associated with the emergence of tumors. To include the molecular causes of cancer, competition with ceRNA (endogenous RNA) networks is crucial. However, the exact processes they contribute to TACE HCC remain uncertain. The purpose of this study was tantamount to investigating the possible function of ceRNA networks and m6A regulators in patients with TACE HCC.
Genes Associated with m6A were discovered using the TACE GEO (Gene Expression Omnibus) dataset. An additional estimate of M6A-associated DEGs (differentially expressed genes) was used to create a predictive response model, which is required. LncRNA-miRNA and miRNA-mRNA interactions were then predicted, the regulatory ceRNA network was set up using Cytoscape software, and target genes were identified using GEPIA online analysis. The connection between immunological checkpoints, immune cell marker genes, and target genes for immune cells was also examined.
The detection of 4 m6A-associated DEGs, the development and evaluation of 2 Machine learning models, and the development of risk models that accurately predicted the response rate of specific patients. Additionally, we obtained two miRNAs (micro RNAs)and six lncRNAs (Long non-coding RNAs), forming an 8-pair ceRNA network, and the target gene LRPPRC deletion of one copy number and gene expression was highly correlated with the amount of Tregs immune cells. LRPPRC was related positively with NRP1, IRF5, and ITGAM and negatively with CCR7 and CD8B among immune cell marker genes. We also discovered that LRPPRC correlates positively with immune checkpoint CD274 cells.
The response of HCC patients to TACE therapy may be predicted using a model based on four gene expression data. We also developed a ceRNA network for TACE HCC related to m6A, which offered suggestions for more research into its molecular processes and possible prognostic indicators.
中期肝细胞癌（HCC）患者可能从经动脉化疗栓塞术（TACE）中获益。然而，患者疗效差异很大，详细的评估指标尚不清楚。信使核糖核酸（mRNA）中最常见的甲基化改变，即N6-甲基腺苷（m6A），由m6A调节因子控制，其与肿瘤的发生有关。为了纳入癌症的分子病因，与竞争性内源RNA（ceRNA）网络的相互作用至关重要。然而，它们在TACE治疗HCC中的确切作用仍不确定。本研究的目的等同于探究ceRNA网络和m6A调节因子在接受TACE治疗的HCC患者中的可能作用。
利用TACE基因表达综合数据库（GEO）数据集发现与m6A相关的基因。使用另一种对与M6A相关的差异表达基因（DEG）的估计来创建所需的预测反应模型。然后预测长链非编码RNA（lncRNA）-微小RNA（miRNA）和miRNA- mRNA的相互作用，使用Cytoscape软件建立调控ceRNA网络，并通过GEPIA在线分析确定靶基因。还研究了免疫检查点、免疫细胞标记基因和免疫细胞靶基因之间的联系。
检测到4个与m6A相关的DEG，开发并评估了2个机器学习模型，以及准确预测特定患者反应率的风险模型。此外，我们获得了2个miRNA和6个lncRNA，形成了一个8对的ceRNA网络，并且一个拷贝数缺失的靶基因LRPPRC以及基因表达与调节性T细胞（Tregs）免疫细胞数量高度相关。在免疫细胞标记基因中，LRPPRC与神经纤毛蛋白1（NRP1）、干扰素调节因子5（IRF5）和整合素αM（ITGAM）呈正相关，与趋化因子受体7（CCR7）和CD8B呈负相关。我们还发现LRPPRC与免疫检查点CD274细胞呈正相关。
可以使用基于四个基因表达数据的模型预测HCC患者对TACE治疗的反应。我们还为与m6A相关的TACE治疗HCC开发了一个ceRNA网络，为进一步研究其分子机制和可能的预后指标提供了建议。
