肾透明细胞癌预后免疫相关基因的生物信息学筛选。
Bioinformatics screening of prognostic immune-related genes in renal clear cell carcinoma.
发表日期:2024 May 23
作者:
Kai Cui, He Song, Han Zhang, Peiyu Sun
来源:
GENES & DEVELOPMENT
摘要:
本研究旨在利用生物信息学来识别透明细胞肾细胞癌 (ccRCC) 中的预后免疫相关基因,特别关注 LILRB3。它评估了LILRB3在ccRCC中的表达、其与患者预后的关系以及其作为预测生存的生物标志物的潜力,从而为ccRCC的诊断提供初步依据。利用癌症基因组图谱 (TCGA) 数据集和免疫基因集,我们寻找在 ccRCC 中表达升高的免疫相关基因。对72个正常组织样本和531个ccRCC样本进行分析,以倍数变化(FC) > 2和P值 < 0.01的筛选标准鉴定差异基因。采用生存分析和受试者工作特征 (ROC) 曲线分析来发现与 ccRCC 预后和诊断相关的基因。在 cBioPortal 的协助下,以 |r|≥0.5 为截止值的 Pearson 相关分析评估了与 LILRB3 共表达的基因。 DAVID 在线工具对 LILRB3 共表达基因进行了功能和通路富集分析。利用TIMER和TCIA数据库探讨LILRB3对肿瘤微环境中免疫浸润的影响及其与关键免疫检查点的关系。筛选TCGA数据库发现ccRCC中有3719个上调差异基因,其中355个重叠的免疫相关基因。对这 355 个基因的生存分析显示,其中 100 个基因具有显着的生存影响。 ROC曲线分析精确定位了诊断效率最高的前10个基因,其中包括LILRB3。 LILRB3 作为 Cox 风险回归模型的独立风险因素出现。 GO 和 KEGG 分析将 LILRB3 与各种生物过程联系起来,包括趋化因子信号通路、免疫反应、抗原加工和呈递、炎症反应、T 细胞共刺激和信号转导。 LILRB3显着影响ccRCC免疫浸润,并与PD-1、LAG3、IDO1、PD-L1、CTLA4、TIM3、TIGIT和VISTA等多个免疫检查点呈正相关。 LILRB3 在 ccRCC 中的表达水平高于正常组织,并且与患者不良预后相关。它在 RCC 微环境免疫浸润中的重要作用表明,LILRB3 可以作为 ccRCC 治疗和预后的新靶点,强调其诊断和预后意义。© 2024。作者,获得植物遗传学研究所独家许可波兰科学院。
This study aims to harness bioinformatics to identify prognostic immune-related genes in clear cell renal cell carcinoma (ccRCC), focusing particularly on LILRB3. It evaluates LILRB3's expression in ccRCC, its association with patient prognosis, and its potential as a biomarker for predicting survival, thereby providing a preliminary basis for the diagnosis of ccRCC. Utilizing The Cancer Genome Atlas (TCGA) datasets and an immune gene set, we sought immune-related genes with elevated expression in ccRCC. Seventy-two normal tissue samples and 531 ccRCC samples were analyzed, and differential genes were identified with a screening criterion of fold change (FC) > 2 and P value < 0.01. Survival analysis and receiver operating characteristic (ROC) curve analysis were employed to discover genes of prognostic and diagnostic relevance to ccRCC. Pearson correlation analysis with a cutoff of |r|≥ 0.5, facilitated by cBioPortal, assessed genes co-expressed with LILRB3. The DAVID online tool conducted functional and pathway enrichment analyses for LILRB3-coexpressed genes. The TIMER and TCIA databases were utilized to explore LILRB3's influence on immune infiltration in the tumor microenvironment and its relation to key immunological checkpoints. Screening the TCGA database revealed 3719 up-regulated differential genes in ccRCC, with 355 overlapping immune-related genes. Survival analysis of these 355 genes revealed 100 with significant survival impact. ROC curve analysis pinpointed the top 10 genes, including LILRB3, with the highest diagnostic efficiency. LILRB3 emerged as an independent risk factor from the Cox risk regression model. GO and KEGG analyses linked LILRB3 to various biological processes, including chemokine signaling pathways, immunological response, antigen processing and presentation, inflammatory response, T cell co-stimulation, and signal transduction. LILRB3 significantly affected ccRCC immune infiltration and correlated positively with several immunological checkpoints, such as PD-1, LAG3, IDO1, PD-L1, CTLA4, TIM3, TIGIT, and VISTA. LILRB3 shows higher expression levels in ccRCC than in normal tissues and correlates with poor patient prognosis. Its impactful role in the immune infiltration of the RCC microenvironment suggests that LILRB3 could serve as a novel target for ccRCC treatment and prognosis, underlining its diagnostic and prognostic significance.© 2024. The Author(s), under exclusive licence to Institute of Plant Genetics Polish Academy of Sciences.