ZFYVE28可作为肿瘤预后的生物标志物并抑制肿瘤增殖  

ZFYVE28 is a Prognostic Biomarker and Inhibit Tumor Proliferation

作　　者：黄书晨 苑萌萌 崔冰[1] 闫宇鹏[1] 王红蕊 汪一波[1] HUANG Shu-chen;YUAN Meng-meng;CUI Bing;YAN Yu-peng;WANG Hong-rui;WANG Yi-bo(State Key Laboratory of Cardiovascular Disease,Fuwai Hospital,National Center for Cardiovascular Diseases,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,102308,China)

机构地区：[1]中国医学科学院北京协和医学院国家心血管病中心中国医学科学院阜外医院心血管疾病国家重点实验室,北京市102308

出　　处：《中国分子心脏病学杂志》2020年第2期3322-3329,共8页Molecular Cardiology of China

基　　金：国家自然科学基金(81770424/81970430);心血管疾病国家重点实验室(2018ZR-10/2018kf-04)。

摘　　要：目的ZFYVE28(zinc finger FYVE-type containing 28)是EGFR(epidermal growth factor receptor)的负调节因子,ZFYVE28能够促进原癌基因EGFR的胞内降解。然而,ZFYVE28与肿瘤预后及肿瘤增殖之间的相关性仍需要进一步研究。方法通过Oncomine数据库和TIMER数据库分析ZFYVE28在各种类型肿瘤中的表达水平。然后使用PrognoScan,Kaplan-Meier Plotter和GEPIA评估ZFYVE28表达对肿瘤临床预后的影响。接着使用TIMER数据库比较ZFYVE28的表达水平与肿瘤免疫浸润之间的相关性。通过GEPIA分析ZFYVE28与多种受体酪氨酸激酶(RTKs)的表达相关性。最后通过构建荷瘤小鼠模型验证ZFYVE28影响肿瘤增殖的假说。结果通过分析Oncomine数据库和TIMER数据库我们发现ZFYVE28在肿瘤组织中的表达水平显著低于癌旁组织。对Kaplan-Meier Plotter数据库中的Pan-cancer队列的RNA测序数据分析显示,ZFYVE28的高水平表达与更好的总生存期(OS)相关。结合对TCGA数据库和PrognoScan数据库的分析,我们认为ZFYVE28与多种肿瘤的临床预后显著相关。对肿瘤组织进行基因表达相关性分析,发现ZFYVE28的表达水平与多种RTKs的表达显著相关,这些RTKs参与包括细胞增殖在内的众多生物学过程。最后,动物实验的结果证实ZFYVE28能够抑制体内的肿瘤增殖。结论研究表明ZFYVE28与肿瘤患者的临床预后密切相关,并能够影响体内的肿瘤增殖。此外,ZFYVE28可能具有广谱的促RTKs降解的功能,这有待后续机制实验的验证。本研究对ZFYVE28参与肿瘤增殖做了初步探索,并证明了ZFYVE28能够作为肿瘤患者预后的生物标志物。Objective ZFYVE28(zinc finger FYVE-type containing 28)is a negative regulator factor of EGFR(epidermal growth factor receptor).ZFYVE28 in the absence of ubiquitination can promote intracellular degradation of EGFR,a protooncogene.However,it remains to be explored with respect to the relationship of ZFYVE28 expression with tumor prognosis and tumor proliferation.Methods ZFYVE28 expression in various types of tumors was analyzed firstly by searching Oncomine database and TIMER database.PrognoScan,Kaplan-Meier Plotter,and GEPIA were then searched to assess the impact of ZFYVE28 expression on clinical outcomes of tumor patients.Subsequently,the correlation between ZFYVE28 expression and tumor immune invasion was compared according to TIMER database.Further analysis was carried out concerning the relationship between ZFYVE28 expression and various genes encoding receptor tyrosine kinases(RTKs)based on GEPIA.Finally,the hypothesis of ZFYVE28 participating in tumor cell proliferation was verified by the establishment of tumor bearing mice model.Results By analyzing the Oncomine database and TIMER database,we found that the expression of ZFYVE28 in tumor tissues was significantly lower than that in the corresponding adjacent tissues.According to the analysis results of RNA-seq data of Pan-cancer cohort in Kaplan-Meier Plotter,high ZFYVE28 expression was related to better overall survival.Data screened from TCGA and PrognoScan supported that ZFYVE28 was significantly related to the prognosis of various cancers.Furthermore,correlation analysis of gene expression in tumor tissue revealed that ZFYVE28 expression was significantly related to the expression of multiple RTKs.Besides,these RTKs were involved in many biological processes including cell proliferation.Finally,the results of animal experiment confirmed that ZFYVE28 could inhibit tumor proliferation in vivo.Conclusion ZFYVE28 may be intimately correlated with the prognosis of tumor patients and can affect tumor proliferation in vivo.Meanwhile,ZFYVE28 correlates obvio

关 键 词：ZFYVE28 肿瘤增殖 癌症 疾病预后 表达分析 

分 类 号：R730.2[医药卫生—肿瘤]