RIPK2免疫调控及临床预后的生物信息学分析

The bioinformatics analysis of RIPK2 immune regulation and clinical prognosis

目的探讨受体相互作用丝氨酸/苏氨酸蛋白激酶2(RIPK2)参与免疫调控通路及临床预后的作用。方法通过TIMER、cBioPortal、Human Protein Atlas(HPA)和UALCAN和STRING等数据库对RIPK2在组织中的定位和表达,及其在肿瘤免疫浸润、免疫调控和生存预后中的作用进行分析。结果(1)RIPK2主要由激酶和CARD结构域构成,第18~298位氨基酸是其激酶结构,第435~526位氨基酸是CARD结构域;与正常组织细胞比较,RIPK2在大部分恶性肿瘤中高表达,其中在子宫内膜上皮癌和人黑色素瘤细胞系(hTERT-HME1)中表达最高。相比胶质瘤(GBM)和透明细胞癌(KIRC),在结肠癌(COAD)组织突变率和表达水平较高。(2)免疫组化和荧光染色结果显示,RIPK2定位在胞质,在不同肿瘤组织中RIPK2的表达和AIM2、CASP1、GSDMD、NLRP3、NOD1和NOD2蛋白表达呈正相关。(3)PPI网络图显示,RIPK2参与免疫调控,包括NOD样、NLRP3炎性小体、AIM2炎性小体和细胞焦亡相关通路。(4)RIPK2的表达与免疫渗漏和临床预后有关,在COAD和KIRC中,RIPK2的表达与CD_(8)^(+)、CD_(4)^(+)T细胞、Neutrophil细胞存在相关性。(5)生存分析曲线显示,RIPK2高表达与KIRC患者的预后生存相关,且高表达RIPK2的KIRC患者生存期缩短。结论RIPK2在COAD、GBM和KIRC等恶性肿瘤中高表达,参与调控免疫渗漏、预测肿瘤预后和生存分析,推测RIPK2可作为一个关键的候选基因,在免疫调控、指导临床预后和治疗恶性肿瘤中发挥重要作用。

Objective To investigate the role of receptor interacting serine/threonine kinase 2(RIPK2)in immune regulatory pathway and clinical prognosis.Methods TIMER,cBioPortal,Human Protein Atlas(HPA)and UALCAN and STRING databases were used to analyze the localization and expression of RIPK2 in tissues and its role in tumor invasion,immune regulation and survival prognosis.Results(1)RIPK2 was mainly composed of kinase and CARD domain.Amino acids from 18 to 298 were its kinase structure,and 435 to 526 were CARD domain.Compared with normal tissue or cells,RIPK2 was highly expressed in most malignant tumors.Compared with glioma and clear cell carcinoma,the mutation rate and expression levels were higher in colon cancer tissues,with the highest expressions in endometrial epithelial carcinoma and human melanoma cell line(HTERT-HME1).(2)Immunohistochemistry and fluorescence staining showed that RIPK2 was localized in the cytoplasm,and positively correlated with protein expressions of AIM2,CASP1,GSDMD,NLRP3,NOD1 and NOD2 in different tumor tissues.(3)PPI network diagram showed that RIPK2 was involved in immune regulation,including NOD-like,NLRP3 inflammasome,AIM2 inflammasome and proptosis related pathways.(4)RIPK2 expression was related to immune leakage.RIPK2 was highly expressed in most malignant tumors compared to normal tissue cells,with the highest expression in endometrial epithelial carcinoma and human melanoma cell line(hTERT-HME1).Compared to glioma(GBM)and clear cell carcinoma(KIRC),the tissue mutation rate and expression level were higher in colon cancer(COAD).(5)High expression of RIPK2 was found to be associated with prognostic survival in KIRC patients in the survival analysis,and the survival was significantly reduced in KIRC patients with high RIPK2 expression.Conclusion RIPK2 is highly expressed in common COAD,GBM,and KIRC malignancies,which are involved in the regulation of immune leakage,tumor prognosis and survival analysis.RIPK2 could be a key candidate gene that plays an important role in immune regulation,guiding clinical prognosis,and treatment of malignant tumors.