IVIM-DWI与3D-ASL定量参数评估METTL14调控人结直肠癌裸鼠皮下移植瘤细胞增殖和血管生成状态的实验研究  

The Experiment Research of IVIM-DWI and 3D-ASL Quantitative Parameters to Evaluate METTL14 Regulating on Xenograft Growth and Angiogenesis in Nude Mice with Human Colorectal Cancer Cells

作　　者：张中原 韦巍 贾好东 方昕 董江宁 ZHANG Zhongyuan;WEI Wei;JIA Haodong(Xinxiang Medical University,Xinxiang,Henan Province 453003,P.R.China)

机构地区：[1]新乡医学院,453003 [2]中国科学技术大学附属第一医院西区影像科,合肥230001

出　　处：《临床放射学杂志》2023年第5期855-862,共8页Journal of Clinical Radiology

基　　金：中央高校基本科研业务费专项资金资助项目(编号:YD2150002001)。

摘　　要：目的探讨定量参数体素内不相干运动扩散加权成像(IVIM-DWI)和三维自旋动脉标记(3D-ASL)灌注成像技术动态评估甲基转移酶样14(METTL14)调控人结直肠癌(CRC)裸鼠皮下移植瘤细胞增殖和血管生成状态的可行性。方法采用免疫组织化学(IHC)检测52例临床标本CRC组织和邻近癌旁组织中的METTL14的表达。取20只5周龄裸鼠,随机平均分成两组,分别皮下注射稳定干扰METTL14基因的HCT116细胞和空载质粒(未干扰METTL14基因)对照HCT116细胞,建立METTL14敲低组和对照组的皮下移植瘤模型。两组裸鼠成瘤后分别进行MRI平扫、IVIM-DWI与3D-ASL检查。测量的IVIM-DWI参数有表观扩散系数(ADC)、真性扩散系数(D)、灌注相关的扩散系数(D^(*))、灌注分数(f)和3D-ASL参数血流量(BF)值,并将其与皮下瘤体积、质量、Ki-67和CD34的免疫组织化学染色结果进行相关性分析。结果IHC染色结果表明癌旁组织中METTL14蛋白表达较高,而肿瘤组织中表达较低。METTL14敲低组皮下移植瘤的体积和质量均大于对照组,差异存在统计学意义(t值分别为5.312、5.535,P值均<0.05)。METTL14敲低组的ADC值、D值均低于对照组,而D^(*)值、f值以及BF值均高于对照组,差异均有统计学意义(t值分别为-2.802、-4.311、4.992、4.141和6.498,P值均<0.05)。METTL14敲低组皮下移植瘤的Ki-67增殖指数和微血管密度(MVD)计数明显高于对照组,均存在统计学差异(t值为9.387和7.3,P值<0.05)。通过Pearson相关性分析,METTL14敲低组的D^(*)值、BF值与MVD计数及皮下移植瘤体积、重量之间均呈正相关性(P<0.05),而ADC值、D值与Ki-67增殖指数及皮下瘤体积、重量之间均呈负相关性(P<0.05)。结论IVIM-DWI与3D-ASL技术能够定量监测METTL14调控裸鼠皮下移植瘤的水分子扩散运动与微循环灌注的信息,无创性反映肿瘤组织内微血管生成与细胞密集度的状态,可用于评估METTL14对CRC皮下移植瘤生长的调控作用,�Objectivee To explore the feasibility of intravoxel incoherent motion diffusion weighted imaging(IVIMDWI)and three-dimensional arterial spin labeling(3D-ASL)perfusion imaging technique dynamically evaluating the regulation of METTL14 on the cell proliferation and angiogenesis of subcutaneous xenograft in nude mice of human colorectal cancer.Methods Immunohistochemistry(IHC)was used to detect METTL14 expression in CRC and adjacent tissues of 52 clinical specimens.Twenty 5-week-old nude mice were randomly divided into two groups.HCT116 cells with stable interference of METTL14 gene and control HCT116 cells with empty plasmid(no interference of METTL14 gene)were subcutaneously injected to the two group of nude mice,respectively,to establish subcutaneous transplanted tumor models of METTL14 knockdown group and control group.After that these mice carrying subcutaneous tumor preoperatively underwent plain MRI for IVIM-DWI and 3D-ASL examinations.IVIM-DWI quantitative parameters(ADC,D,D^(*),f)and 3D-ASL parameters(blood flow,BF)value were measured and optimal maps were reconstructed.Correlation analysis was conducted between all parameters and subcutaneous tumor volume,mass,Ki-67 and CD34 staining indices.Results IHC staining results showed that the expression of METTL14 protein was higher in adjacent tissues but lower in tumor tissues.Compared with control group,the volume and mass of subcutaneous xenograft in the Mettll4 knockdown group were much greater,with statistically significant differences(t value was 5.312,5.535,P<0.05).Besides,the values of ADC and D in the Mettl14 knockdown group were lower than those in the control group,while D^(*),F and BF values were higher than the counterpart,and the differences were statistically significant(t values were-2.802,-4.311,4.992,4.141 and 6.498,respectively,all P<0.05).Ki-67 and CD34 immunohistochemical results showed that the proliferation index and the microvessel density(MVD)count of xenograft in the Mettl14 knockdown group was significantly higher than that in the cont

关 键 词：裸鼠 结直肠癌 皮下移植瘤 体素内不相干运动扩散加权成像 三维自旋动脉标记法灌注成像 

分 类 号：R735.34[医药卫生—肿瘤]