Suppr超能文献

去泛素化酶相关mRNA特征模型预测肝细胞癌患者的预后并影响其免疫微环境:一项观察性研究

Deubiquitinase-associated mRNA signature model predicts prognosis and influences the immune microenvironment in patients with hepatocellular carcinoma: An observational study.

作者信息

Liu Haodong, Liu Yinan, Liang Shijie, Yang Zheng, Mo Wuning

机构信息

Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Medicine of Guangxi Department of Education, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang, China.

Department of Pediatrics, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China.

出版信息

Medicine (Baltimore). 2025 Jul 25;104(30):e43442. doi: 10.1097/MD.0000000000043442.

Abstract

Liver hepatocellular carcinoma (LIHC) represents a category of malignant neoplasms that present a considerable risk to public health. Recent studies have increasingly focused on the biological roles of messenger RNAs (mRNAs) linked to deubiquitinating enzymes in the context of LIHC. These deubiquitinating enzyme-associated mRNAs have been utilized to construct a prognostic model for this type of cancer. Prognostic mRNAs associated with LIHC were identified through univariate Cox regression and co-expression analysis. A clinical risk prediction model was established utilizing multivariate Cox regression and least absolute shrinkage and selection operator analysis, resulting in the stratification of patients into high-risk and low-risk categories. The model's accuracy and clinical significance were assessed through various methodologies, including receiver operating characteristic curves, area under the curve calculations, univariate and multivariate Cox regression analyses, principal component analysis, t-distributed stochastic neighbor embedding, Kaplan-Meier Plotter, gene set enrichment analysis, tumor mutation burden analysis, immune infiltration analysis, and drug sensitivity prediction. The UALCAN database was employed to validate the aberrant expression of the identified characteristic genes, and consistency clustering analysis was conducted to delineate and compare the molecular subtypes of LIHC. The risk model we developed exhibited robust predictive capabilities, with the high-risk cohort demonstrating reduced survival rates across various clinical contexts. This group also presented a more pronounced tumor mutation burden, exhibited stronger correlations with immune cell populations, and displayed heightened activation of numerous immune checkpoints. Notably, the characteristic genes (CBX2, ERGIC3, GNL2) were found to be aberrantly overexpressed in the cancer genome atlas cohort, correlating with unfavorable prognostic outcomes, and may play a role in tumor invasion and metastasis. Consistency clustering analysis revealed 3 distinct subtypes (C1, C2, C3), with subtype C3 showing elevated activation levels at the majority of immune checkpoints in comparison to subtypes C2 and C1, as well as increased sensitivity to pharmacological agents such as 5-fluorouracil and afatinib. The prognostic assessment model developed in this research offers an innovative approach for the identification of novel prognostic markers in patients diagnosed with (LIHC).

摘要

肝细胞癌(LIHC)是一类对公众健康构成重大风险的恶性肿瘤。最近的研究越来越关注与去泛素化酶相关的信使核糖核酸(mRNA)在LIHC背景下的生物学作用。这些与去泛素化酶相关的mRNA已被用于构建此类癌症的预后模型。通过单变量Cox回归和共表达分析确定了与LIHC相关的预后mRNA。利用多变量Cox回归和最小绝对收缩和选择算子分析建立了临床风险预测模型,从而将患者分为高风险和低风险类别。通过各种方法评估了该模型的准确性和临床意义,包括受试者工作特征曲线、曲线下面积计算、单变量和多变量Cox回归分析、主成分分析、t分布随机邻域嵌入、Kaplan-Meier Plotter、基因集富集分析、肿瘤突变负担分析、免疫浸润分析和药物敏感性预测。使用UALCAN数据库验证所鉴定特征基因的异常表达,并进行一致性聚类分析以描绘和比较LIHC的分子亚型。我们开发的风险模型具有强大的预测能力,高风险队列在各种临床情况下的生存率均降低。该组还表现出更明显的肿瘤突变负担,与免疫细胞群体的相关性更强,并且显示出多种免疫检查点的激活增强。值得注意的是,发现特征基因(CBX2、ERGIC3、GNL2)在癌症基因组图谱队列中异常过表达,与不良预后结果相关,并且可能在肿瘤侵袭和转移中起作用。一致性聚类分析揭示了3种不同的亚型(C1、C2、C3),与C2和C1亚型相比,C3亚型在大多数免疫检查点处显示出更高的激活水平,并且对5-氟尿嘧啶和阿法替尼等药物的敏感性增加。本研究中开发的预后评估模型为识别诊断为(LIHC)的患者中的新型预后标志物提供了一种创新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/515e/12303482/7a3c1de40277/medi-104-e43442-g001.jpg

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验