4-NQQ诱导小鼠舌癌形成过程中的血清差异蛋白筛选  

Screening of serum differential proteins by iBT quantification proteomics during 4-NQQ induced tongue cancer in mice

作　　者：李邦 王飞 张亚军 刘来奎[3] 孙应明[1] Li Bang;Wang Fei;Zhang Yajun(Dept of Stomatology,Wuxi Clinical College of Anhui Medical University,Wuxi 214044;Dept of Stomatology,The 101st Military Hospital,Wuxi 214000)

机构地区：[1]安徽医科大学无锡临床学院口腔科,无锡214044 [2]中国人民解放军第101医院口腔科,无锡214044 [3]南京医科大学附属口腔医院口腔基础教研室,南京210029

出　　处：《安徽医科大学学报》2018年第10期1513-1517,共5页Acta Universitatis Medicinalis Anhui

基　　金：江苏省自然科学基金(编号:BK20171483)

摘　　要：目的通过蛋白组学i BT技术,筛选舌癌形成过程中血清的差异表达蛋白,以期筛选出舌癌早期诊断的肿瘤标志物。方法使用4-硝基喹啉-1-氧化物(4-NQQ)诱导小鼠舌黏膜癌变,收取小鼠舌癌形成过程中特定时间点血清行蛋白组学分析。结果在24周时成功诱导小鼠舌黏膜癌变并有部分小鼠出现了浸润癌,血清蛋白组学分析结果显示,在8周和16周对比组中显示癌相关蛋白胶原蛋白α-1高表达,纤连蛋白(FN)低表达;在16周和24周的对比组中显示癌相关蛋白FHL1、FN、热休克蛋白84b(HSP 84b)、Serine/threonine-protein(PP2A)、(14-3-3)低表达。通路分析结果显示在舌癌形成过程中,RAS通路(RAS)、NF-κB通路(NF-κB)、磷脂酰肌醇3-激酶(PI3K)、JAK-STAT通路(JAKSTAT)癌相关通路异常。结论在蛋白组学的结果中发现的差异蛋白FHL1、FN、HSP、PP2A、14-3-3等在舌癌形成的过程中异常表达,有可能成为舌癌诊断的标志物,异常表达的通路如:NF-κB、PI3K、JAK-STAT等则有可能成为舌癌免疫治疗重要的靶点。Objective Screening differentially expressed proteins in serum of tongue carcinoma by proteomics iBT technique to screen for tumor markers for early diagnosis of tongue cancer.Methods 4-nitroquinoline-1-oxide(4-NQQ)was used to induce tongue cancer in mice and serum proteomic analysis was performed at a specific time point during the development of tongue cancer in mice.Results At 24 weeks,mice were successfully induced into tongue cancer and some mice developed invasive carcinoma.The results of serum proteomics analysis were as follows,in the compare groups of 8 weeks vs 16 weeks,cancer-associated collagen alpha-1 protein was up-regulated and Fibronectin(FN)was down-regulated.FHL1,FN,heat shock protein 84b(HSP 84b),serine/threonine-protein(PP2A)and(14-3-3)were found down-regulated in the compare groups of 16 weeks vs 24 weeks.Signal pathway analysis showed that cancer-related signaling pathways such as RAS,NF-κB,PI3K and JAK-STAT were abnormal in tongue carcinogenesis.Conclusion According to the results of iBT quantification analysis,FHL1,FN,HSP,PP2A,14-3-3,etc.are found abnormally express in the process of tongue tumorigenesis.Those proteins may become markers for the diagnosis of tongue cancer.The abnormal pathways such as:NF-κB,PI3K,JAK-STAT,etc.may become important targets for immunotherapy of tongue cancer.

关 键 词：舌癌 动物模型 4-硝基喹啉-1-氧化物 C57BL/6小鼠 肿瘤标志物 舌癌免疫治疗 

分 类 号：R739.86[医药卫生—肿瘤]