Table2_Determining the Prognostic Value of Spliceosome-Related Genes in Hepatocellular Carcinoma Patients.DOCX

Background: The spliceosome plays an important role in mRNA alternative splicing and is aberrantly expressed in several tumors. However, the potential roles of spliceosome-related genes in the progression of hepatocellular carcinoma (HCC) remain poorly understood.
Materials and Methods: Patient data were acquired from public databases. Expression differences and survival analyses were used to assess the importance of spliceosome-related genes in HCC prognosis. To explore the potential regulatory mechanisms of these genes, a protein-protein interaction network was constructed and screened using univariate and multivariate Cox regression and random forest analyses. This was used to create a five-gene prognostic model. The prognostic value and predictive power of the five-gene signature were assessed using the Kaplan-Meier and time-dependent receiver operating characteristic analyses in the training set. These results were further validated in an independent external set. To facilitate clinical application, a nomogram was prepared to predict the overall survival of HCC patients. The relative expression of five genes was detected using real-time quantitative polymerase chain reaction.
Results: The analysis revealed that LSM1-7, SNRPB, SNRPD1-3, SNRPE, SNRPF, SNRPG, and SNRPN could be used as prognostic biomarkers in HCC patients. Moreover, the five-gene risk model could clearly distinguish between the high-and low-risk groups. Furthermore, the risk model was associated with the tumor mutation burden, immune cell infiltration of CD8+ T cells, natural killer T cells, M2 macrophages, and immune checkpoint inhibitors, which also demonstrated the predictive efficacy of this risk model in HCC immunotherapy.
Conclusion: Spliceosome-related genes and the five-gene signature could serve as novel prognostic biomarkers for HCC patients, aiding clinical patient monitoring and follow-up.

背景：剪接体（spliceosome）在mRNA可变剪接中发挥关键作用，且在多种肿瘤中存在异常表达。然而，剪接体相关基因在肝细胞癌（hepatocellular carcinoma, HCC）进展中的潜在作用仍有待阐明。
材料与方法：患者数据获取自公共数据库。通过表达差异分析与生存分析，评估剪接体相关基因在肝细胞癌预后评估中的重要性。为探究这些基因的潜在调控机制，本研究构建了蛋白质-蛋白质相互作用（protein-protein interaction, PPI）网络，并通过单变量Cox回归、多变量Cox回归及随机森林分析进行筛选，以此建立五基因预后模型。在训练队列中，采用卡普兰-迈耶（Kaplan-Meier）分析与时间依赖性受试者工作特征（time-dependent receiver operating characteristic, t-ROC）分析，评估该五基因特征的预后价值与预测效能，并在独立外部验证队列中对上述结果进行复现验证。为推动临床转化应用，本研究构建了列线图（nomogram）以预测肝细胞癌患者的总生存期。通过实时定量聚合酶链反应（real-time quantitative polymerase chain reaction, qRT-PCR）检测了五个目标基因的相对表达水平。
结果：分析结果显示，LSM1-7、SNRPB、SNRPD1-3、SNRPE、SNRPF、SNRPG及SNRPN可作为肝细胞癌患者的潜在预后生物标志物。此外，该五基因风险模型可有效区分高风险组与低风险组人群。进一步分析表明，该风险模型与肿瘤突变负荷、CD8+ T细胞、自然杀伤T细胞、M2型巨噬细胞的免疫浸润水平及免疫检查点抑制剂治疗响应均存在显著关联，证实了该风险模型在肝细胞癌免疫治疗中的预测效能。
结论：剪接体相关基因及该五基因特征可作为肝细胞癌患者新型预后生物标志物，可为临床患者的病情监测与随访管理提供参考依据。