Gd-EOB-DTPA增强MRI预测肝细胞癌基因治疗靶点表达水平的研究

Study of predicting target therapy related gene expression level for hepatocellular carcinoma using Gd-EOB-DTPA enhanced MRI

目的分析Gd-EOB-DTPA动态增强MRI术前预测HCC基因表达水平的可能性。方法回顾性分析91例单发HCC术前Gd-EOB-DTPA增强MRI特征,包括肿瘤最大径、信号均匀性、肿瘤包膜、肿瘤边缘、瘤内血管、动脉中期瘤周强化、肝胆特异期瘤周低信号、ADC值、T_1减低值比率。采用免疫组化评估术后HCC标本基因治疗靶点(B-Raf、Raf-1、VEGFR2、VEGFR3)表达水平。采用秩和检验、Spearman相关及多因素Logistic回归分析各MRI特征与B-Raf、Raf-1、VEGFR2、VEGFR3表达水平的相关性。结果单因素分析结果表明,肿瘤包膜状态(P=0.000)、瘤内血管(P=0.002)与B-Raf基因表达水平密切相关;肿瘤包膜状态(P=0.001)、瘤内血管(P=0.013)与Raf-1基因表达水平密切相关;各MRI特征均与VEGFR2、VEGFR3基因表达水平无相关性。多因素Logistic回归模型分析显示肿瘤包膜不完整(P=0.002,OR=11.870,95%CI:2.473~56.975)或无肿瘤包膜(P=0.004,OR=15.750,95%CI:2.373~104.537)是HCC病灶B-Raf基因高表达的独立危险因素;肿瘤包膜不完整(P=0.000,OR=11.250,95%CI:3.206~39.474)或无肿瘤包膜(P=0.040,OR=5.556,95%CI:1.078~28.635)是HCC病灶Raf-1基因高表达的独立危险因素。结论利用Gd-EOB-DTPA增强MRI可术前预测HCC的B-Raf、Raf-1基因表达水平。

Objective To investigate the feasibility of predicting target therapy related gene expression level in hepatocellular carcinoma(HCC)using preoperative Gd-EOB-DTPA enhanced MRI.Methods 91 patients with solitary HCC who underwent preoperative Gd-EOB-DTPA enhanced MRI were prospectively analyzed.Features including tumor size,signal homogeneity,tumor capsule,tumor margin,intratumoral vessels,peritumoral enhancement in mid-arterial phase,peritumoral hypointensity during hepatobiliary phase,apparent diffusion coefficients(ADCs),and T1 reduction rate between pre-and post-contrast enhancement images were assessed.HCC target therapy related gene(B-Raf,Raf-1,VEGFR2,VEGFR3)expression level in excision specimens were evaluated using immunohistochemical staining.Correlation between these MRI features and B-Raf,Raf-1,VEGFR2,VEGFR3 gene expression level were analyzed by Rank sum test,Spearman correlation and multivariate logistic regression so as to establish a prediction model.Results Univariate analysis showed that tumor incomplete or non capsule(P=0.000),intratumoral vessels(P=0.002)were significantly related with the B-Raf gene expression level,and tumor capsule status(P=0.001),intratumoral vessels(P=0.013)were significantly correlated with the Raf-1 gene expression level.There was no significant association between the expression level of VEGFR2,VEGFR3 and all the MRI features.Multivariate logistic regression analysis demonstrated that incomplete tumor capsule(P=0.002,OR=11.870,95%CI:2.473-56.975)or non capsule(P=0.004,OR=15.750,95%CI:2.373-104.537)were independent risk factors of HCC with high B-Raf gene expression level,and incomplete tumour capsule(P=0.000,OR=11.250,95%CI:3.206-39.474)or non capsule(P=0.040,OR=5.556,95%CI:1.078-28.635)were independent risk factors of HCC with high Raf-1 gene expression level.Conclusion Preoperative Gd-EOB-DTPA-enhanced MRI has predictive value for expression level of B-Raf amd Raf-1 gene.