基于生物信息学分析ADCY1基因在肾透明细胞癌中的表达及临床意义  

Bioinformatics-based analysis of ADCY1 gene expression in clear cell renal cell carcinoma and its clinical significance

作　　者：张琳 王东文[1,3] ZHANG Lin;WANG Dongwen(First Clinical Medical College of Shanxi Medical University,First Hospital of Shanxi Medical University,Taiyuan 030000;Department of Urology,First Hospital of Shanxi Medical University,Taiyuan 030000;Department of Urology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Shenzhen 518116,China)

机构地区：[1]山西医科大学第一临床医学院,山西太原030000 [2]山西医科大学第一医院泌尿外科,山西太原030000 [3]国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院深圳医院泌尿外科,广东深圳518116

出　　处：《现代泌尿外科杂志》2024年第6期547-554,共8页Journal of Modern Urology

基　　金：国家癌症中心重点课题项目(No.SZ2020ZD003);山西省研究生教育创新项目(No.2023SJ142)。

摘　　要：目的通过生物信息学方法分析腺苷酸环化酶1(ADCY1)在肾透明细胞癌(ccRCC)中的表达水平、临床意义及预后价值。方法基于UALCAN数据库获得数据分析ADCY1在ccRCC组织中的表达水平及与病理特征的相关性。通过GEPIA2数据库分析ADCY1在ccRCC中的预后价值。通过HPA数据库分析ADCY1的蛋白质表达水平和三维结构。基于Genecard数据库分析ADCY1的亚细胞定位。利用STRING数据库获得ADCY1相互作用蛋白,并使用R软件分析其功能富集。通过cBioPortal数据库分析ADCY1基因的突变情况。基于R语言分析ADCY1在ccRCC中的免疫细胞浸润情况。通过实时荧光定量聚合酶链式反应(qRT-PCR)和免疫组织化学染色初步验证ADCY1在ccRCC临床组织样本中的表达水平。结果ADCY1在ccRCC中表达降低,且与ccRCC病理分期、分级显著相关,ADCY1低表达的患者总生存率(OS)和无病生存率(RFS)低。ADCY1主要表达于细胞的质膜、细胞外、细胞核。ADCY1与吗啡成瘾、昼夜节律调节、多巴胺能突触、3′,5′-单磷酸腺苷(cAMP)信号通路密切相关。ADCY1在ccRCC中的主要突变类型为错义突变。ADCY1与ccRCC中的CD4 T细胞和巨噬细胞浸润呈正相关。验证实验结果显示,在ccRCC临床组织样本中ADCY1基因和蛋白表达相较于正常组织下降。结论ADCY1可能是ccRCC的新预后标志物和潜在临床治疗靶点。Objective To analyze the expression level,clinical significance and prognostic value of adenylate cyclase 1(ADCY1)in clear cell renal cell carcinoma(ccRCC).Methods ADCY1 expression level and correlation with pathological features were analyzed with UALCAN database.The prognostic value of ADCY1 in ccRCC was analyzed with GEPIA2 database.The protein expression level and three-dimensional structure of ADCY1 were analyzed with HPA database.The subcellular localization of ADCY1 was analyzed with Genecard database.ADCY1 interacting proteins were obtained using the STRING database and enriched with R software.Mutations of ADCY1 gene were analyzed with cBioPortal database.Immune cell infiltration of ADCY1 in ccRCC was analyzed with R language.ADCY1 expression level in ccRCC tissues was verified with quantitative real-time polymerase chain reaction(qRT-PCR)and immunohistochemical staining.Results ADCY1 was down-regulated in ccRCC and significantly correlated with pathological staging and grading.Patients with low ADCY1 expression had poorer overall and disease-free survival.ADCY1 was mainly expressed in the plasma membrane,extracellular,and nucleus of the cells.ADCY1 was closely related to morphine addiction,regulation of circadian rhythm,dopaminergic synapses,and cAMP signaling pathway.The main mutation type of ADCY1 in ccRCC was missense mutation.ADCY1 was positively correlated with CD4 T cell and macrophage infiltration in ccRCC.The gene and protein expressions of ADCY1 were decreased in ccRCC tissues.Conclusion ADCY1 is a new prognostic marker and potential clinical therapeutic target for ccRCC.

关 键 词：肾透明细胞癌 腺苷酸环化酶1 生物信息学分析 预后标志物 治疗靶点 

分 类 号：R737.11[医药卫生—肿瘤]