一种新型的超级增强子相关风险模型,用于预测肝细胞癌的预后并指导个性化治疗。
A novel super-enhancer-related risk model for predicting prognosis and guiding personalized treatment in hepatocellular carcinoma.
发表日期:2024 Sep 02
作者:
Qing Wu, Ping Li, Xuan Tao, Nan Lin, BinBin Mao, Xianhe Xie
来源:
MOLECULAR & CELLULAR PROTEOMICS
摘要:
我们的研究致力于开发基于超级增强子相关基因 (SERG) 的强大预测特征,其双重目标是预测肝细胞癌 (HCC) 的生存结果和评估肿瘤免疫微环境 (TiME)。HCC RNA 测序数据从癌症基因组图谱 (TCGA) 中检索,365 名患者按 1:1 的比例随机分配到训练组或测试组。 HCC 的 SERG 是从 Super-Enhancer 数据库 (SEdb) 下载的。在训练集的基础上,识别了 SERG 签名,并通过内部和外部验证 (GSE14520) 集确认了其预后价值。我们随后检查了模型的潜在功能丰富和肿瘤免疫浸润的程度。此外,我们还进行了体外实验来深入研究CBX2基因的生物学功能。建立并验证了包括CBX2、TPX2、EFNA3、DNASE1L3和SOCS2在内的SE相关预后模型。根据该风险模型,高危组患者的预后明显较差,其免疫细胞浸润与低危组存在显着差异。此外,高危组表现出肿瘤相关病理通路的显着富集。 SERGs 特征通常可用于筛选可能对免疫治疗有反应的 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,我们发现CBX2基因表达的下调会抑制HCC细胞活力、迁移和细胞周期进展,同时促进细胞凋亡。我们利用SERGs开发了一种新型HCC预后模型,表明高危评分的患者不仅面临着预后较差,但也可能表现出对免疫检查点抑制剂(ICIs)的治疗反应减弱。该模型旨在根据每位患者的个体需求制定个性化治疗策略,从而改善 HCC 患者的整体临床结果。此外,CBX2 是 HCC 治疗干预的有前途的候选者。© 2024。作者。
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).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.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.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.© 2024. The Author(s).