中国免疫学杂志2024,Vol.40Issue(5) :918-924.DOI:10.3969/j.issn.1000-484X.2024.05.004

肾透明细胞癌VSIG4表达及其与免疫细胞浸润的相关性研究

Analysis of VSIG4 expression in clear cell renal cell carcinoma and its correlation with tumor infiltrating immune cells

刘杭丰 刘盛露 段连瑞 昝丽坤 马彦杰 杨利军
中国免疫学杂志2024,Vol.40Issue(5) :918-924.DOI:10.3969/j.issn.1000-484X.2024.05.004

肾透明细胞癌VSIG4表达及其与免疫细胞浸润的相关性研究

Analysis of VSIG4 expression in clear cell renal cell carcinoma and its correlation with tumor infiltrating immune cells

刘杭丰 1刘盛露 1段连瑞 2昝丽坤 3马彦杰 4杨利军5
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作者信息

  • 1. 山西医科大学基础医学院药理学教研室,晋中 030600
  • 2. 山西医科大学基础医学院生物化学与分子生物学教研室,晋中 030600
  • 3. 山西省肿瘤医院病理科,太原 030001
  • 4. 山西医科大学第一附属医院泌尿外科,太原 030001
  • 5. 山西医科大学基础医学院药理学教研室,晋中 030600;山西医科大学靶向药物研究中心,晋中 030600
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摘要

目的:探究VSIG4在肾透明细胞癌(ccRCC)中的表达及其与免疫细胞浸润和预后的关系.方法:从癌症基因组图谱(TCGA)数据库中下载ccRCC的RNA-seq数据和患者相应的临床数据;通过Wilcoxon秩和检验分析ccRCC及正常肾组织中VSIG4 mRNA表达水平;Wilcoxon秩和或Kruskal-Wallis秩和检验分析VSIG4表达与临床病理参数的相关性;Kaplan-Meier法分析VSIG4表达与患者预后的相关性;基因集富集分析(GSEA)探究VSIG4在ccRCC中参与的信号通路;使用R软件运行CIBERSORT算法分析VSIG4表达与肿瘤浸润免疫细胞的相关性;Western blotting检测人正常肾上皮细胞系293T和人肾癌细胞系ACHN、A-498、786-O、OS-RC-2中VSIG4蛋白表达.结果:VSIG4在ccRCC中的表达水平显著高于正常组织(P<0.05);VSIG4的表达与患者远处转移分期和淋巴结转移分期显著相关(P<0.05);生存分析显示,VSIG4高表达组患者总体生存率显著低于低表达组患者(P<0.05);GSEA富集分析结果显示,VSIG4主要在凋亡、趋化因子信号通路、细胞黏附分子等信号通路富集;VSIG4表达与M1巨噬细胞呈负相关(r<0,P<0.05),而与M2巨噬细胞呈正相关(r>0,P<0.05);免疫印迹结果表明,肾癌细胞中VSIG4蛋白表达均高于人正常肾上皮细胞系.结论:VSIG4在ccRCC中高表达,且与预后呈负相关,可能成为ccRCC患者预后的生物标志物.

Abstract

Objective:To explore expression of VSIG4 in clear cell renal cell carcinoma(ccRCC)and its correlation with immune cells infiltration and prognosis.Methods:RNA-seq data of ccRCC and corresponding clinical data of patients were downloaded from The Cancer Genome Atlas(TCGA)database.Wilcoxon rank-sum test was used to analyze VSIG4 mRNA expression in ccRCC and normal renal tissues.Correlation between VSIG4 expression and clinicopathological parameters was analyzed by Wilcoxon rank-sum or Kruskal-Wallis rank-sum test.Kaplan-Meier method was used to analyze the correlation between VSIG4 expression and progno-sis of patients.Gene set enrichment analysis(GSEA)was used to explore the signaling pathway of VSIG4 in ccRCC.Correlation between VSIG4 level and tumor infiltrating immune cells was analyzed via CIBERSORT in R software.Western blotting was used to detect VSIG4 protein level in human renal epithelial cell line 293T,and human renal carcinoma cell line ACHN,A498,786-O and OS-RC-2.Results:Expression level of VSIG4 in ccRCC was significantly higher than that in normal tissues(P<0.05).VSIG4 expression was significantly correlated with the stages of distant metastasis and lymph node metastasis(P<0.05).Overall survival rate of patients with high VSIG4 expression was significantly lower than that of patients with low expression(P<0.05).GSEA enrichment analysis showed that VSIG4 was mainly enriched in apoptosis,chemokine signaling pathway,cell adhesion molecules and other signaling path-ways.VSIG4 expression was negatively correlated with M1 macrophages(r<0,P<0.05),while positively correlated with M2 macro-phages(r>0,P<0.05).Western blotting results showed that expression of VSIG4 in renal cell carcinoma cells was higher than that in normal renal cells.Conclusion:VSIG4 is highly expressed in ccRCC,and is negatively associated with prognosis,which may become a prognostic biomarker for ccRCC patients.

关键词

肾透明细胞癌/VSIG4/肿瘤浸润免疫细胞/生物信息学分析

Key words

Clear cell renal cell carcinoma/VSIG4/Tumor-infiltrating immune cells/Bioinformatics analysis

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基金项目

国家自然科学基金(81972325)

山西省应用基础研究计划青年项目(202103021223226)

出版年

2024
中国免疫学杂志
中国免疫学会,吉林省医学期刊社

中国免疫学杂志

CSTPCD北大核心
影响因子:0.926
ISSN:1000-484X
参考文献量31
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