Su Guomiao, Li Yanxi, Wang Juan, Liu Shiyue, Pan Guoqing, Zhan Dong
Department of Pathology, First Affiliated Hospital of Kunming Medical University, Kunming, China.
Clinical Laboratory, Yunnan Province Third People's Hospital, Kunming, China.
BMC Gastroenterol. 2025 Jul 1;25(1):452. doi: 10.1186/s12876-025-04031-6.
Hepatocellular carcinoma (HCC) represents the most prevalent histological subtype of primary liver cancer. This study aimed to establish a miRNA-related prognostic genes signature, providing a theoretical framework for prognosis and therapy in patients with HCC. The miRNA-correlated (MIRcor) genes were identified through correlation analysis of miRNA-mRNA relationships from three databases. Consensus clustering was then applied to HCC samples based on these MIRcor genes. Differentially expressed genes (DEGs) between HCC and normal samples, as well as between subtypes with the most significant survival differences, were extracted. Subtype-and-tumor common DEGs were identified by intersecting these DEGs. Prognostic genes were derived using univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses. A risk model was developed with the The Cancer Genome Atlas-Hepatocellular Carcinoma (TCGA-HCC) dataset and validated in the International Cancer Genome Consortium-Hepatocellular Carcinoma (ICGC-HCC) dataset, while independent prognostic predictors were confirmed through Cox analysis. Additionally, an immune microenvironment analysis was conducted to compare high- and low-risk groups. From the subtype-and-tumor common DEGs, five prognostic genes were identified and used to construct a prognostic gene signature. Expression of these genes was further validated at both protein and mRNA levels via Western blotting and Reverse Transcription Polymerase Chain Reaction (RT-PCR). The risk score and T stage emerged as reliable independent prognostic predictors. We observed significant differences in the abundance of 11 types of immune cells between the high-risk and low-risk groups. All five prognostic genes were expressed at significantly higher levels in normal liver tissues than in HCC tumor tissues. A risk model based on these genes offers a theoretical basis and valuable reference for HCC management.
肝细胞癌（HCC）是原发性肝癌中最常见的组织学亚型。本研究旨在建立一种与miRNA相关的预后基因特征，为HCC患者的预后和治疗提供理论框架。通过对来自三个数据库的miRNA - mRNA关系进行相关性分析，确定了与miRNA相关的（MIRcor）基因。然后基于这些MIRcor基因对HCC样本进行一致性聚类。提取HCC与正常样本之间以及生存差异最显著的亚型之间的差异表达基因（DEG）。通过对这些DEG进行交叉分析，确定亚型和肿瘤共同的DEG。使用单变量Cox和最小绝对收缩和选择算子（LASSO）回归分析得出预后基因。利用癌症基因组图谱 - 肝细胞癌（TCGA - HCC）数据集建立风险模型，并在国际癌症基因组联盟 - 肝细胞癌（ICGC - HCC）数据集中进行验证，同时通过Cox分析确认独立的预后预测因子。此外，进行了免疫微环境分析以比较高风险和低风险组。从亚型和肿瘤共同的DEG中，鉴定出五个预后基因并用于构建预后基因特征。通过蛋白质印迹和逆转录聚合酶链反应（RT - PCR）在蛋白质和mRNA水平进一步验证了这些基因的表达。风险评分和T分期是可靠的独立预后预测因子。我们观察到高风险组和低风险组之间11种免疫细胞的丰度存在显著差异。所有五个预后基因在正常肝组织中的表达水平均显著高于HCC肿瘤组织。基于这些基因的风险模型为HCC管理提供了理论基础和有价值的参考。
