Department of Plastic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
Int J Mol Sci. 2024 Nov 7;25(22):11969. doi: 10.3390/ijms252211969.
Hepatocellular carcinoma is characterized by high recurrence rates and poor prognosis. Cancer stem cells contribute to tumor heterogeneity, treatment resistance, and recurrence. This study aims to identify key genes associated with stemness and immune cell infiltration in HCC. We analyzed RNA sequencing data from The Cancer Genome Atlas to calculate mRNA expression-based stemness index in HCC. A weighted gene co-expression network analysis was performed to identify stemness-related gene modules. A single-sample gene set enrichment analysis was used to evaluate immune cell infiltration. Key genes were validated using RT-qPCR. The mRNAsi was significantly higher in HCC tissues compared to adjacent normal tissues and correlated with poor overall survival. WGCNA and subsequent analyses identified 10 key genes, including minichromosome maintenance complex component 2, cell division cycle 6, forkhead box M1, NIMA-related kinase 2, Holliday junction recognition protein, DNA topoisomerase II alpha, denticleless E3 ubiquitin protein ligase homolog, maternal embryonic leucine zipper kinase, protein regulator of cytokinesis 1, and kinesin family member C1, associated with stemness and low immune cell infiltration. These genes were significantly upregulated in HCC tissues. A functional enrichment analysis revealed their involvement in cell cycle regulation. This study identified 10 key genes related to stemness and immune cell infiltration in HCC. These genes, primarily involved in cell cycle regulation, may serve as potential targets for developing more effective treatments to reduce HCC recurrence and improve patient outcomes.
肝细胞癌的特点是复发率高、预后差。癌症干细胞导致肿瘤异质性、治疗耐药和复发。本研究旨在鉴定与 HCC 干性和免疫细胞浸润相关的关键基因。我们分析了癌症基因组图谱中的 RNA 测序数据，以计算 HCC 中基于 mRNA 表达的干性指数。进行了加权基因共表达网络分析以鉴定干性相关基因模块。使用单样本基因集富集分析评估免疫细胞浸润。使用 RT-qPCR 验证关键基因。与相邻正常组织相比，HCC 组织中的 mRNAsi 显著升高，与总体生存不良相关。WGCNA 及随后的分析确定了 10 个关键基因，包括微小染色体维持复合物成分 2、细胞分裂周期 6、叉头框 M1、NIMA 相关激酶 2、 Holliday 连接识别蛋白、DNA 拓扑异构酶 IIα、牙本质蛋白 E3 泛素蛋白连接酶同源物、母胚亮氨酸拉链激酶、细胞分裂调控蛋白 1 和驱动蛋白家族成员 C1，与干性和低免疫细胞浸润相关。这些基因在 HCC 组织中显著上调。功能富集分析表明它们参与细胞周期调控。本研究鉴定了 10 个与 HCC 干性和免疫细胞浸润相关的关键基因。这些基因主要参与细胞周期调控，可能成为开发更有效治疗方法以降低 HCC 复发和改善患者预后的潜在靶点。
