现代泌尿外科杂志2024,Vol.29Issue(5) :459-465,475.DOI:10.3969/j.issn.1009-8291.2024.05.017

肾透明细胞癌中双硫死亡核心基因SLC7A11的孟德尔随机化及生物信息学分析

Mendelian randomization and bioinformatics analysis of the disulfidoptosis core gene SLC7A11 in clear cell renal cell carcinoma

李子峰 陈博宏 黄昊翔 冯聪 曾津 陈炜 吴大鹏
现代泌尿外科杂志2024,Vol.29Issue(5) :459-465,475.DOI:10.3969/j.issn.1009-8291.2024.05.017

肾透明细胞癌中双硫死亡核心基因SLC7A11的孟德尔随机化及生物信息学分析

Mendelian randomization and bioinformatics analysis of the disulfidoptosis core gene SLC7A11 in clear cell renal cell carcinoma

李子峰 1陈博宏 1黄昊翔 1冯聪 1曾津 1陈炜 1吴大鹏1
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作者信息

  • 1. 西安交通大学第一附属医院泌尿外科,陕西西安 710061
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摘要

目的 分析溶质载体家族7成员11(SLC7A11)在肾透明细胞癌(ccRCC)发生、发展中的作用及其预后价值.方法 采用两样本孟德尔随机化分析以识别与ccRCC风险存在因果关系的基因.使用来自UCSC Xena泛癌队列的RNA测序数据及临床数据分析SLC7A11的表达及预后意义.使用TCGA-KIRC数据(训练集)进行基因集富集分析(GSEA).随后通过逐步Cox回归分析建立了基于SLC7A11的预后模型,并在E-MATB-1980队列(验证集)中进行了外部验证.结果 孟德尔随机化分析显示,SLC7A11水平升高会加重ccRCC的患病风险(HR=1.27,95%CI:1.15~1.40,P<0.001).SLC7A11在各种肿瘤中过表达,并与高T分期和较差的生存预后相关(P<0.05).GSEA显示SLC7A11富集在增殖和转移相关通路,包括E2F和上皮-间质转化信号通路.SLC7A11预后模型在训练集(1、3、5年AUC=0.78、0.73、0.71)和验证集(1、3、5年AUC=0.70、0.71、0.72)中均显示出强大的预测性能.结论 SLC7A11作为ccRCC的潜在生物标志物和治疗靶点,为精准医学提供了新视角.

Abstract

Objective To investigate the role of solute carrier family 7 member 11(SLC7A11)in the pathogenesis and progression of clear cell renal cell carcinoma(ccRCC)and its prognostic significance.Methods Mendelian randomization analysis was employed to identify genes causally associated with the risk of ccRCC.The expression patterns and prognostic relevance of SLC7A11 were assessed using RNA sequencing data and clinical information obtained from the UCSC Xcna pan-cancer cohort.Gene set enrichment analysis(GSEA)was conducted using data from The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma(TCGA-KIRC)dataset(training set).A prognostic model based on SLC7A11 was then developed using stepwise Cox regression and validated externally in the E-MTAB-1980 cohort(validation set).Results Elevated level of SLC7A11 was associated with an increased risk of ccRCC(HR=1.27,95%CI:1.15-1.40,P<0.001).SLC7A11 was overexpressed in various tumors and correlated with higher T stage and poorer survival(P<0.05).GSEA demonstrated that SLC7A11 was enriched in pathways related to proliferation and metastasis,including E2F and epithelial-to-mesenchymal transition signaling pathways.Moreover,the SLC7A11 prognostic model exhibited robust predictive performance in both the training set(1-,3-,and 5-year AUC=0.78,0.73,0.71,respectively)and the external validation set(1-,3-,and 5-year AUC=0.70,0.71,0.72,respectively).Conclusion SLC7A11 can be a potential biomarker and therapeutic target for ccRCC,offering novel perspectives for precision medicine.

关键词

溶质载体家族7成员11/肾透明细胞癌/生信分析/孟德尔随机化/生物标志物/治疗靶点

Key words

solute carrier family 7 member 11(SLC7A11)/clear cell renal cell carcinoma/bioinformation analysis/mendelian randomization/biomarker/therapeutic target

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出版年

2024
现代泌尿外科杂志
西安交通大学

现代泌尿外科杂志

CSTPCD
影响因子:1.106
ISSN:1009-8291
参考文献量20
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