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IQGAP3在宫颈癌中的表达及其对患者预后和免疫浸润的影响OACSTPCD

Expression of IQGAP3 in cervical cancer and its effect on prognosis and immune infiltration

中文摘要英文摘要

目的 探讨在宫颈癌中IQ结构域GTP酶激活蛋白3(IQ motif-containing GTPase activating protein 3,IQGAP3)的表达水平及其与患者预后、免疫浸润水平和生物学功能之间的关系.方法 使用基因表达谱交互式分析(Gene Expression Profiling Interactive Analysis,GEPIA)数据库分析宫颈癌组织和正常对照组织中IQGAP3 mRNA的表达水平.利用人类蛋白质图谱(Human Protein Atlas,HPA)数据库提供的免疫组化切片探索了IQGAP3蛋白在宫颈癌组织及正常对照组织中的表达情况.采用免疫组化检测宫颈癌组织芯片中IQGAP3蛋白表达,并采用Kaplan-Meier法绘制生存曲线.从癌症基因组图谱(The Can-cer Genome Atlas,TCGA)数据库获得了306例宫颈癌的RNAseq数据以及相应的临床信息,对IQGAP3相关的差异基因进行了富集分析,包括基因本体论(gene ontology,GO)和京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析.采用EPIC算法对宫颈癌组织中免疫细胞的浸润情况进行分析,并分析IQGAP3高表达组和低表达组免疫检查点相关基因的表达情况.结果 与正常对照组织比较,宫颈癌组织中IQGAP3的mRNA及蛋白高表达(P<0.05).Ka-plan-Meier生存曲线分析显示,IQGAP3蛋白高表达组宫颈癌患者总生存期及无进展生存期明显降低(P<0.05),IQGAP3表达水平的升高与淋巴结转移、较高的T分期及复发之间存在明显的相关性(P<0.05).通过富集分析发现,IQGAP3可能参与间隙连接、铁死亡、Hippo信号通路的负调控等信号通路及生物学过程.此外,IQGAP3的表达与CD4+T细胞、巨噬细胞和NK细胞类型有关,在IQGAP3高表达组中,部分免疫检查点相关基因(CTLA4、HAVCR2、LAG3)的表达显著下调.结论 IQGAP3在宫颈癌中高表达,与患者的预后和免疫特征相关.

Objective To investigate the expression of IQ motif-containing GTPase activating protein 3(IQGAP3)in cervical cancer and its correlation with prognosis,immune infiltration levels and biological functions.Methods The level of IQGAP3 mRNA in cer-vical cancer tissues and normal control tissues was analyzed using the Gene Expression Profiling Interactive Analysis(GEPIA)database.The expression of IQGAP3 protein in cervical cancer tissues and normal control tissues was analyzed using immunohistochemical sections based on the Human Protein Atlas(HPA)database.The expression of IQGAP3 protein in cervical cancer tissue microarrays was detected by immunohistochemistry,and Kaplan-Meier survival curves were plotted.RNAseq data of 306 cases of cervical cancer and corresponding clinical information were obtained from The Cancer Genome Atlas(TCGA)database.Differentially expressed genes associated with IQGAP3 were enriched and analyzed by gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.Using the EPIC algorithm,the immune cell infiltration in cervical cancer tissues was analyzed and the expression of immune checkpoint-related genes in high and low IQGAP3 expression groups was examined.Results Compared to normal control tissues,both mRNA and protein levels of IQGAP3 were significantly upregulated in cervical cancer(P<0.05).Kaplan-Meier survival curve analysis indicated that the overall survival and the progression-free survival of the patients with high IQGAP3 protein expres-sion were significantly reduced(P<0.05).Elevated IQGAP3 expression was notably correlated with lymph node metastasis,higher T stage,and recurrence.Enrichment analysis suggested that IQGAP3 might be involved in signaling pathways and biological processes such as gap junctions,ferroptosis,and the negative regulation of Hippo signaling pathway.Additionally,IQGAP3 expression was associated with CD4+T cells,macrophages,and NK cells.In IQGAP3 high expression group,the expressions of certain immune checkpoint-related genes(CTLA4,HAVCR2,LAG3)were significantly downregulated.Conclusion IQGAP3 is highly expressed in cervical cancer and correlated with prognosis and immune characteristics.

芦娇娇;甄帅;江玉

西安交通大学第一附属医院医学影像科,西安 710061西安交通大学第一附属医院转化医学中心西安交通大学第一附属医院妇产科

临床医学

宫颈癌IQGAP3生物信息学预后免疫浸润

cervical cancerIQGAP3bioinformaticsprognosisimmune infiltration

《山西医科大学学报》 2024 (009)

1105-1112 / 8

西安交通大学第一附属医院科研发展基金项目(2020QN-27)

10.13753/j.issn.1007-6611.2024.09.002

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