背景:我们的研究致力于开发一种基于超级增强子相关基因(SERGs)的强大预测特征,具有预测生存结果和评估肝细胞癌(HCC)肿瘤免疫微环境(TiME)的双重目标。
方法:从癌症基因组图谱(TCGA)检索HCCRNA测序数据,365例患者以1:1的比例被随机分配到训练或测试组.HCC的SERGs从超级增强子数据库(SEdb)下载。在训练集的基础上,确定了SERGs签名,其预后价值通过内部和外部验证(GSE14520)组得到证实。我们随后检查了该模型的潜在功能富集和肿瘤免疫浸润程度。此外,我们进行了体外实验来研究CBX2基因的生物学功能。
结果:建立并验证了包括CBX2,TPX2,EFNA3,DNASE1L3和SOCS2的SE相关预后模型。根据这个风险模型,高风险组患者的预后明显较差,免疫细胞浸润与低危组差异显著。此外,高危人群表现出肿瘤相关病理通路的显著富集.SERGs签名通常可用于筛选可能对免疫疗法有反应的HCC患者,因为风险评分与肿瘤免疫功能障碍和排除(TIDE)评分之间存在正相关。此外,CBX2基因表达的下调被发现抑制HCC细胞活力,迁移,和细胞周期进程,同时促进细胞凋亡。
结论:我们利用SERGs开发了一种新的HCC预后模型,这表明高风险评分的患者不仅预后较差,而且对免疫检查点抑制剂(ICIs)的治疗反应也可能减弱。该模型旨在针对每个患者的个性化需求定制个性化治疗策略,从而改善HCC患者的整体临床结果。此外,CBX2是HCC治疗干预的有希望的候选者。
BACKGROUND: Our research endeavored to develop a robust predictive signature grounded in super-enhancer-related genes (SERGs), with the dual objectives of forecasting survival outcomes and evaluating the tumor immune microenvironment (TiME) in hepatocellular carcinoma (HCC).
METHODS: HCC RNA-sequencing data were retrieved from The Cancer Genome Atlas (TCGA), and 365 patients were randomly assigned to training or testing sets in 1:1 ratio. SERGs of HCC were downloaded from Super-Enhancer Database (SEdb). On the basis of training set, a SERGs signature was identified, and its prognostic value was confirmed by internal and external validation (GSE14520) sets. We subsequently examined the model for potential functional enrichment and the degree of tumor immune infiltration. Additionally, we carried out in vitro experiments to delve into the biological functions of CBX2 gene.
RESULTS: An SE-related prognostic model including CBX2, TPX2, EFNA3, DNASE1L3 and SOCS2 was established and validated. According to this risk model, patients in the high-risk group had a significantly worse prognosis, and their immune cell infiltration was significantly different from that of low-risk group. Moreover, the high-risk group exhibited a significant enrichment of tumor-associated pathological pathways. The SERGs signature can generally be utilized to screen HCC patients who are likely to respond to immunotherapy, as there is a positive correlation between the risk score and the Tumor Immune Dysfunction and Exclusion (TIDE) score. Furthermore, the downregulation of the CBX2 gene expression was found to inhibit HCC cell viability, migration, and cell cycle progression, while simultaneously promoting apoptosis.
CONCLUSIONS: We developed a novel HCC prognostic model utilizing SERGs, indicating that patients with high-risk score not only face a poorer prognosis but also may exhibit a diminished therapeutic response to immune checkpoint inhibitors (ICIs). This model is designed to tailor personalized treatment strategies to the individual needs of each patient, thereby improving the overall clinical outcomes for HCC patients. Furthermore, CBX2 is a promising candidate for therapeutic intervention in HCC.