一种新型肾透明细胞癌焦亡相关基因预后风险模型的建立和验证

王万里; 任伟南; 赵千; 石贞玉; 厉永强

doi:10.16098/j.issn.0529-1356.2022.05.012

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解剖学报 ›› 2022, Vol. 53 ›› Issue (5) : 620-627. DOI: 10.16098/j.issn.0529-1356.2022.05.012

一种新型肾透明细胞癌焦亡相关基因预后风险模型的建立和验证

王万里¹ 任伟南¹ 赵千¹ 石贞玉^2* 厉永强^2*

作者信息 +

A novel defined pyroptosis-related genes prognostic risk model for predicting the prognosis of kidney renal clear cell carcinoma#br#

#br#

WANG Wan-li¹ REN Wei-nan¹ ZHAO Qian¹ SHI Zhen-yu^2* LI Yong-qiang ^2*

Author information +

文章历史 +

摘要

目的建立一种新型肾透明细胞癌焦亡相关基因风险模型。方法从癌症基因组图谱(TCGA)数据库、基因型组织表达(GTEx)数据库分别下载了522例肾透明细胞癌(KIRC)患者和72例正常组织样本。对TCGA和GTEx的数据进行差异分析，采用单因素和多因素COX回归分析以及LASSO Cox回归分析构建基因风险模型。使用国际癌症基因组联盟 (ICGC)数据作为外部验证数据集。对TCGA_KIRC队列的高、低风险组进行基因本体论(GO)富集分析与京都基因与基因组百科全书(KEGG)通路富集分析，探讨高、低风险组之间基因功能和通路的差异。利用CIBERSORT数据库探讨高、低风险组的免疫浸润情况。结果通过差异分析，得到13个差异表达的焦亡相关基因。采用单因素、多因素和LASSO Cox回归分析构建1个6基因风险模型。Kaplan-Meier分析结果显示，两个队列中高风险组生存时间均短于低风险组。在TCGA_KIRC队列中，1、2、3年曲线下面积(AUC)分别为0.710、0.683和0.727。在ICGC_RECA队列中，1、2、3年曲线下面积为0.592、0.531和0.545。独立预后分析显示，风险分数是1个独立预后因素。GO功能富集分析和KEGG通路富集分析结果表明，其主要与免疫和炎症反应相关。肿瘤的免疫浸润结果表明，高风险组中CD4+T细胞调节性T细胞、自然杀伤细胞、单核细胞、M2巨噬细胞和嗜酸性粒细胞浸润水平低，B细胞、CD8⁺T细胞、滤泡辅助性T细胞浸润水平高。结论细胞焦亡相关基因可能在KIRC肿瘤免疫中发挥重要作用，联合与细胞焦亡相关的6基因风险模型可以为KIRC患者的个性化治疗方案提供预测依据。

Abstract

Objective To establish a novel defined pyroptosis-related genes risk model of kidney renal clear cell carcinoma. Methods Data of 522 patients with KIRC and 72 normal tissue samples were respectively downloaded from the Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx) database. Differential analysis was performed between data of TCGA and GTEx. Univariate Cox regression analysis, multivariate Cox regression analyses and LASSO Cox regression analysis were used to establish a prognostic risk model. Data from the International Cancer Genome Consortium (ICGC) database was used as an external validation cohort. Gene ontology (GO) enrichment analysis and Kyoto Encylopedia of Genes and Genomes (KEGG) pathway analysis were used to explore the differences of gene functions and pathways between high-risk and low-risk groups. The CIBERSORT database was used to explore the immune infiltration of high-risk and low-risk groups. Results Through differential analysis, we obtained 13 differentially expressed pyroptosis-related genes. Univariate Cox regression analysis, multivariable Cox regression analyses and LASSO Cox regression analysis were used to establish a 6-gene risk model. Kaplan-Meier analysis indicated that survival time in high-risk group was shorter than low-risk group in both cohorts. The area under the curve (AUC) was 0.710 for 1-year, 0.683 for 2-year, and 0.727 for 3-year survival in the TCGA_KIRC cohort. The AUC was 0.592 for 1-year, 0.531 for 2-year, and 0.545 for 3-year survival in the ICGC_RECA cohort. Independent prognostic analysis indicated that risk score was an independent prognostic factor. GO enrichment analysis and KEGG pathway analysis showed that it was mainly associated with immune and inflammatory responses. The result of tumor immune infiltration showed that the high-risk group had low infiltration levels of regulatory T cells , natural killer cells, monocytes, M2 macrophages and eosinophils and igh infiltration level of B cells, CD8⁺T cells and follicular helper T cells. Conclusion Pyrolysis-related genes may play an important role in KIRC tumor immunity, and the 6-gene risk model can provide a forecast basis for personalized treatment of patients with KIRC.

导出引用

王万里任伟南赵千石贞玉厉永强. 一种新型肾透明细胞癌焦亡相关基因预后风险模型的建立和验证[J]. 解剖学报. 2022, 53(5): 620-627 https://doi.org/10.16098/j.issn.0529-1356.2022.05.012

WANG Wan-li REN Wei-nan ZHAO Qian SHI Zhen-yu LI Yong-qiang. A novel defined pyroptosis-related genes prognostic risk model for predicting the prognosis of kidney renal clear cell carcinoma#br#

#br#

[J]. Acta Anatomica Sinica. 2022, 53(5): 620-627 https://doi.org/10.16098/j.issn.0529-1356.2022.05.012

中图分类号： R730.1

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