Construction and Validation of a Mutation-Related Model in Papillary Renal Cell Carcinoma and Associated Immune Infiltration.

IF 2.3 4区 医学 Q2 PERIPHERAL VASCULAR DISEASE
Kidney & blood pressure research Pub Date : 2024-01-01 Epub Date: 2024-05-07 DOI:10.1159/000539096
Xiangyun Li, Yang Liu, Luting Zhou, Jianhua Wang, Xiaoqun Yang
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引用次数: 0

Abstract

Background: To improve the clinical evaluation of the prognosis of papillary renal cell carcinoma (PRCC), we screened a model to predict the survival of patients with mutations in related genes.

Methods: We downloaded RNA sequencing information from all patients with PRCC in TCGA. We first analyzed the differences in genes and the enrichment of these differences. Then, by selecting mutant genes, constructing a protein-protein interaction network, least absolute shrinkage and selection operator regression, and multivariable Cox regression, a prognosis model was constructed. Additionally, the model was validated using external data sets. We analyzed the immune infiltration of PRCC and the correlation between the model and popular targets. Finally, we performed tissue microarray analysis and immunohistochemistry to verify the expression levels of the three genes.

Results: We constructed a three-gene (never in mitosis gene A-related kinase 2 [NEK2], centromere protein A [CENPA], and GINS complex subunit 2 [GINS2]) model. The verification results indicated that the model had a good prediction effect. We also developed a visual nomogram. Enrichment analysis revealed the major pathways involved in muscle system processes. Immunoassays showed that the expression level of CENPA was positively correlated with PD-1 and CTLA4 expression levels. Immunohistochemical and tissue microarray results showed that these three genes were highly expressed in PRCC, which was consistent with the predicted results in the database.

Conclusion: We constructed and verified a three-gene model to predict the patient survival. The results show that the model has a good prediction effect.

构建和验证乳头状肾细胞癌突变相关模型及相关免疫浸润。
背景:为了改善乳头状肾细胞癌(PRC)预后的临床评估,我们筛选了一个预测相关基因突变患者生存期的模型:为了改善乳头状肾细胞癌(PRCC)预后的临床评估,我们筛选了一个模型来预测相关基因突变患者的生存率:我们下载了TCGA中所有PRCC患者的RNA测序信息。我们首先分析了基因的差异及其富集情况。然后,通过选择突变基因、构建蛋白-蛋白相互作用网络、拉索回归和多变量考克斯回归,构建了一个预后模型。此外,我们还利用外部数据集对该模型进行了验证。我们分析了 PRCC 的免疫浸润以及模型与流行靶点之间的相关性。最后,我们进行了组织芯片分析和免疫组化,以验证三个基因的表达水平:我们构建了一个三基因(NEK2、CENPA和GINS2)模型。验证结果表明,该模型具有良好的预测效果。我们还建立了一个可视化提名图。富集分析揭示了参与肌肉系统过程的主要通路。免疫测定显示,CENPA的表达水平与PD-1和CTLA4的表达水平呈正相关。免疫组化和组织芯片结果显示,这三个基因在 PRCC 中高表达,这与数据库中的预测结果一致:结论:我们构建并验证了预测患者生存率的三基因模型。结果表明,该模型具有良好的预测效果。
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来源期刊
Kidney & blood pressure research
Kidney & blood pressure research 医学-泌尿学与肾脏学
CiteScore
4.80
自引率
3.60%
发文量
61
审稿时长
6-12 weeks
期刊介绍: This journal comprises both clinical and basic studies at the interface of nephrology, hypertension and cardiovascular research. The topics to be covered include the structural organization and biochemistry of the normal and diseased kidney, the molecular biology of transporters, the physiology and pathophysiology of glomerular filtration and tubular transport, endothelial and vascular smooth muscle cell function and blood pressure control, as well as water, electrolyte and mineral metabolism. Also discussed are the (patho)physiology and (patho) biochemistry of renal hormones, the molecular biology, genetics and clinical course of renal disease and hypertension, the renal elimination, action and clinical use of drugs, as well as dialysis and transplantation. Featuring peer-reviewed original papers, editorials translating basic science into patient-oriented research and disease, in depth reviews, and regular special topic sections, ''Kidney & Blood Pressure Research'' is an important source of information for researchers in nephrology and cardiovascular medicine.
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