■肝细胞癌(HCC)的进展与巨噬细胞极化(MP)有关。我们的目的是在HCC患者中鉴定与MP相关的基因,并基于这些基因开发预后模型。
■我们成功开发了一个由六个MP相关基因(SCN4A,EBF3,ADGRB2,HOXD9,CLEC1B,和MSC)来计算每位患者的风险评分。然后根据中位风险评分将患者分为高危组和低危组。使用Kaplan-Meier和ROC曲线评估MP相关预后模型的性能,这产生了良好的结果。此外,列线图显示良好的临床疗效,并显示与实际观察一致的生存预测.基因集富集分析(GSEA)揭示了与KRAS信号下调相关的途径的富集,G2M检查站,和E2F在高风险组中的目标。相反,与脂肪酸代谢相关的途径,外源性生物代谢,胆汁酸代谢,低危组的脂肪生成丰富。风险评分与侵袭相关基因的数量呈正相关。两组之间的免疫检查点表达存在显著差异。高风险组患者对丝裂霉素C的敏感性增加,顺铂,吉西他滨,雷帕霉素,和紫杉醇,而低危组的患者对阿霉素的敏感性更高。这些发现表明,高危人群可能具有更多的侵袭性HCC,对特定药物的敏感性更高。IHC染色显示SCN4A在HCC组织中的表达水平较高。此外,在HepG2细胞上进行的实验表明,SCN4A表达降低的细胞上清液促进M2巨噬细胞极化标记,THP-1细胞中的CD163。SCN4A表达降低诱导HCC相关基因,而增加的SCN4A表达降低了它们在HepG2细胞中的表达。
■包含六个MPRGs的MP相关预后模型可以有效预测HCC的预后,推断侵入性,并指导药物治疗。SCN4A在HCC中被鉴定为抑制基因。
UNASSIGNED: The progression of hepatocellular carcinoma (HCC) is related to macrophage polarization (MP). Our aim was to identify genes associated with MP in HCC patients and develop a prognostic model based on these genes.
UNASSIGNED: We successfully developed a prognostic model consisting of six MP-related genes (
SCN4A, EBF3, ADGRB2, HOXD9, CLEC1B, and MSC) to calculate the risk score for each patient. Patients were then classified into high- and low-risk groups based on their median risk score. The performance of the MP-related prognostic model was evaluated using Kaplan-Meier and ROC curves, which yielded favorable results. Additionally, the nomogram demonstrated good clinical effectiveness and displayed consistent survival predictions with actual observations. Gene Set Enrichment Analysis (GSEA) revealed enrichment of pathways related to KRAS signaling downregulation, the G2M checkpoint, and E2F targets in the high-risk group. Conversely, pathways associated with fatty acid metabolism, xenobiotic metabolism, bile acid metabolism, and adipogenesis were enriched in the low-risk group. The risk score positively correlated with the number of invasion-related genes. Immune checkpoint expression differed significantly between the two groups. Patients in the high-risk group exhibited increased sensitivity to mitomycin C, cisplatin, gemcitabine, rapamycin, and paclitaxel, while those in the low-risk group showed heightened sensitivity to doxorubicin. These findings suggest that the high-risk group may have more invasive HCC with greater susceptibility to specific drugs. IHC staining revealed higher expression levels of
SCN4A in HCC tissues. Furthermore, experiments conducted on HepG2 cells demonstrated that supernatants from cells with reduced
SCN4A expression promoted M2 macrophage polarization marker, CD163 in THP-1 cells. Reduced
SCN4A expression induced HCC-related genes, while increased
SCN4A expression reduced their expression in HepG2 cells.
UNASSIGNED: The MP-related prognostic model comprising six MPRGs can effectively predict HCC prognosis, infer invasiveness, and guide drug therapy.
SCN4A is identified as a suppressor gene in HCC.