超声造影定量参数水平与原发性肝癌病理特征、癌细胞恶性行为的相关性分析

Correlations between quantitative parameters of contrast-enhanced ultrasound and pathological features,malignant behaviors of primary hepatocellular carcinoma

目的探讨超声造影定量参数水平与原发性肝癌病理特征、癌细胞恶性行为的相关性。方法回顾性选取2016年9月至2019年1月间在福建医科大学附属宁德市医院确诊为原发性肝癌的患者168例作为肝癌组,同期在本院进行体检的健康志愿者50例作为正常对照组。对比两组研究对象的超声造影定量参数[达峰时间(TTP)、峰值强度(PI)、曲线下面积(AUC)]水平,以及肝癌组患者中不同肿瘤分期、不同肿瘤最大直径者超声造影定量参数水平的差异。采用实时荧光定量PCR法检测并对比肝癌组织、癌旁正常组织中肝癌细胞增殖相关基因[脱嘌呤/脱嘧啶核酸内切酶1(APE1)、Ⅳ型胶原蛋白基因α1(COL4A1)、叉头框P2(FOXP2)、缺氧诱导因子-1α(HIF-1α)]、肝癌细胞凋亡相关基因[磷脂酰肌醇-3-激酶(PI3K)、丝苏氨酸蛋白激酶(Akt)、p53、含半胱氨酸的天冬氨酸蛋白水解酶3(caspase-3)、MST1]表达量的差异。采用Pearson检验分析原发性肝癌患者超声造影定量参数水平与癌基因表达量的相关关系。结果肝癌组患者的TTP短于正常对照组,PI、AUC水平高于正常对照组(P<0.05)。Ⅲ~Ⅳ期、肿瘤最大直径≥5 cm的原发性肝癌患者的TTP水平分别低于Ⅰ~Ⅱ期、肿瘤最大直径<5 cm原发性肝癌患者,PI、AUC水平分别高于Ⅰ~Ⅱ期、肿瘤最大直径<5 cm原发性肝癌患者(P<0.05)。肝癌组织中APE1、COL4A1、HIF-1αmRNA的表达量高于癌旁正常组织,FOXP2 mRNA的表达量低于癌旁正常组织;PI3K、Akt mRNA的表达量高于癌旁正常组织,p53、caspase-3、MST1 mRNA的表达量低于癌旁正常组织(P<0.05)。Pearson检验发现,原发性肝癌患者超声造影定量参数TTP、PI、AUC的水平与病理特征、癌细胞恶性行为直接相关。结论原发性肝癌患者超声造影定量参数水平发生显著改变,可间接反映肿瘤病理特征及恶性生物学行为。

Objective To investigate the correlation between quantitative parameters of contrast-enhanced ultrasound and pathological features,malignant behaviors of primary hepatocellular carcinoma(PHC).Methods This retrospective study selected 168 patients diagnosed with PHC in Ningde Hospital affiliated to Fujian Medical University during September 2016 to January 2019 as hepatocellular carcinoma group,and selected 50 healthy volunteers underwent physical examination in our hospital during the same period as normal control group.The contrast-enhanced ultrasound quantitative parameters[time to peak(TTP),peak intensity(PI)and area under the curve(AUC)]of two groups were compared,as well as the differences among patients with different stages and different maximum tumor diameters in PHC group.Real-time fluorescence quantitative PCR was used to detect and compare the expression of APE1,COL4A1,FOXP2,HIF-1a,PI3K,Akt,p53,caspase-3 and MST1 in hepatocellular carcinoma and adjacent normal tissues.Pearson test was used to analyze the correlation between the contrast-enhanced ultrasound quantitative parameters and the expression of oncogene in PHC patients.Results TTP in PHC group was shorter than that in normal control group,PI and AUC levels were higher than those in normal control group(P<0.05).TTP of PHC patients in stage III^IV and with the maximum tumor diameters≥5 cm was shorter than that of patients in stage I^II and<5 cm respectively,while PI and AUC levels were higher than those in stage I^II and<5 cm respectively(P<0.05).The expression of APE1,COL4A1,HIF-1alpha in hepatocellular carcinoma tissues was higher than that in adjacent normal tissues,the expression of FOXP2 was lower than that in adjacent normal tissues;the expression of PI3K and Akt was higher than that in adjacent normal tissues,and the expression of p53,caspase-3 and MST1 was lower than those in adjacent normal tissues(P<0.05).Pearson test showed that the levels of TTP,PI and AUC were directly related to pathological features and malignant behavior of cancer cells.Conclusion The quantitative parameters of contrast-enhanced ultrasound in patients with primary hepatocellular carcinoma are significantly changed,which can indirectly reflect the pathological characteristics and malignant biological behavior of the tumor.