基于生物信息学分析肾透明细...域指蛋白6的表达及临床意义_于建宇.pdf

癌症进展2023 年 3 月第 21 卷第 6 期ONCOLOGY PROGRESS,Mar 2023 V ol.21,No.6*论著*基于生物信息学分析肾透明细胞癌中植物同源结构域指蛋白基于生物信息学分析肾透明细胞癌中植物同源结构域指蛋白6 6的的表达及临床意义表达及临床意义于建宇1，方爱钟2，郑义2，于春娜1，彭怡琛1，林艺1，汪晓敏1#，李文斌1,2#1首都医科大学附属北京天坛医院神经肿瘤综合治疗病区，北京 1000712首都医科大学健康医疗大数据国家研究院，北京 1000690 0摘要摘要：目的目的基于生物信息学分析肾透明细胞癌（KIRC）中植物同源结构域指蛋白 6（PHF6）的表达及临床意义，进而推断 PHF6在 KIRC 中的作用。方法方法通过癌症基因组图谱（TCGA）数据库下载 535例 KIRC 组织及72例正常肾组织的表达数据和临床数据，从基因型-组织表达（GTEx）数据库下载28例正常肾组织的表达数据和临床数据。比较 TCGA、GTEx 数据库中正常肾组织与 KIRC 组织中 PHF6 的表达情况，并比较不同临床特征KIRC患者KIRC组织中PHF6的表达情况。依据PHF6表达水平的中位数，将TCGA数据库中535例KIRC患者分为 PHF6高表达组和 PHF6低表达组，比较两组患者的总生存期（OS）、无进展生存期（PFS）、疾病特异性生存期（DSS）。对PHF6高表达组和PHF6低表达组差异表达的基因进行基因本位（GO）分析，并对PHF6高表达组的基因进行京都基因与基因组百科全书（KEGG）通路富集分析；选取相关基因进行相关性分析，并通过免疫组化法验证PHF6表达与核糖体蛋白S6激酶A6（RSK4）表达的相关性。结果结果与正常肾组织相比，PHF6在KIRC组织中表达下调，PHF6高表达组KIRC患者的中位OS、PFS、DSS均长于PHF6低表达组（P0.05）。通过GO分析可知，差异基因主要集中于体液免疫应答和补体激活等生物学过程，免疫球蛋白复合物和血液微粒等细胞成分，抗原结合、糖胺聚糖结合和硫化合物结合等分子功能上；通过KEGG通路分析可知，PHF6高表达的信号通路中与免疫相关的信号通路活化。相关性分析结果显示，如肌醇 1，4，5-三磷酸 2 型受体（ITPR2）、磷脂酶 A2 组A（PLA2G4A）、前列腺素F受体（PTGFR）、RSK4均与PHF6的表达呈正相关（r=0.52、0.34、0.50、0.42，P0.01）。免疫组化结果显示，RSK4 蛋白的表达与 PHF6 蛋白的表达呈正相关（r=0.557，P0.01）。结论结论与正常肾组织相比，PHF6在KIRC组织中表达下调，PHF6高表达KIRC患者的预后较好，RSK4的表达与PHF6的表达呈正相关。可以根据PHF6的表达水平，对KIRC患者进行干预，有必要将其作为KIRC的候选生物标志物。关键词关键词：植物同源结构域指蛋白6；肾透明细胞癌；预后中图分类号中图分类号：R R737737.1111文献标志码文献标志码：AdoiAdoi：10.11877/j.issn.1672-1535.2023.21.06.06Expression and clinical significance of plant homeodomain finger proteinExpression and clinical significance of plant homeodomain finger protein 6 6 in inrenal clear cell carcinoma based on bioinformatics analysisrenal clear cell carcinoma based on bioinformatics analysisYU Jianyu1,FANG Aizhong2,ZHENG Yi2,YU Chunna1,PENG Yichen1,LIN Yi1,WANG Xiaomin1#,LI Wenbin1,2#1Department of Neuro-Oncology,Cancer Center,Beijing Tiantan Hospital,Capital Medical University,Beijing 100071,China2National Institute for Data Science in Health and Medicine,Capital Medical University,Beijing 100069,ChinaAbstractAbstract:ObjectiveObjectiveBased on bioinformatics analysis of the expression and clinical significance of plant homeodomain finger protein 6(PHF6)in renal clear cell carcinoma(KIRC),the role of PHF6 in KIRC can be inferred.MethodMethodDownloaded the expression and clinical data of 535 KIRC tissues and 72 normal kidney tissues from The Cancer GenomeAtlas(TCGA)database,and 28 normal kidney tissues from the Genotype-Tissue Expression(GTEx)database.Comparedthe expression of PHF6 between normal kidney tissue and KIRC tissue in TCGA and GTEx databases,and compared theexpression of PHF6 in KIRC tissue of KIRC patients with different clinical characteristics.Based on the median expression level of PHF6,535 KIRC patients in the TCGA database were divided into PHF6 high expression group and PHF6low expression group,the overall survival(OS),progression-free survival(PFS),and disease-specific survival(DSS)ofthe two groups were compared.Performed Gene Ontology(GO)enrichment analysis on differentially expressed genes inthe PHF6 high expression group and PHF6 low expression group,and performed Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis on genes in the PHF6 high expression group.Selected relevant genes forcorrelation analysis,and verified the correlation between PHF6 expression and ribosomal protein S6 kinase A6(RSK4)expression through immunohistochemistry.ResultResultCompared with normal kidney tissue,PHF6 expression was downregulated in KIRC tissue,and the median OS,PFS,and DSS of KIRC patients with PHF6 high expression group werelonger than those of the PHF6 low expression group(P0.05).According to GO analysis,differential genes mainly focus基金项目：国家自然科学基金（81972338、82270153）#通信作者（corresponding author），汪晓敏，邮箱：；李文斌，邮箱：603癌症进展2023年3月第21卷第6期on biological processes such as humoral immune response and complement activation,cellular components such as immunoglobulin complex and blood microparticle,and molecular functions such as antigen binding,glycosaminoglycan binding,and sulfur compound binding.Through KEGG pathway analysis,it can be concluded that immune related signalingpathways were activated in the PHF6 highly expressed signaling pathway.The correlation analysis results showed thatthe expression of PHF6 was positively correlated with inositol 1,4,5-triphosphate receptor type 2(ITPR2),phospholipase A2 group IVA(PLA2G4A),prostaglandin F receptor(PTGFR),and RSK4(r=0.52,0.34,0.50,0.42,P0.01).The immunohistochemical results showed positive correlation between the expression of RSK4 protein and the expression ofPHF6 protein(r=0.557,P0.01).ConclusionConclusionCompared with normal kidney tissue,PHF6 expression is downregulatedin KIRC tissue.KIRC patients with PHF6 high expression have a better prognosis,and the expression of RSK4 is positively correlated with PHF6 expression.It is necessary to intervene in KIRC patients based on the expression level ofPHF6 as a candidate biomarker for KIRC.Key wordsKey words:plant homeodomain finger protein 6;renal clear cell carcinoma;prognosisOncol Prog,2023,21(6)肾细胞癌是全球常见的恶性肿瘤之一，其中最