甲状腺乳头状癌超声弹性成像参数与微血管密度和癌细胞恶性生物学行为的相关性及其在淋巴结转移评估中的价值

Correlation of UE parameters of PTC and MVD,malignant biological behavior of cancer cells,and its value in the assessment of lymph node metastasis

目的:探讨甲状腺乳头状癌(PTC)超声弹性成像(UE)参数与微血管密度(MVD)、癌细胞恶性生物学行为的相关性及其在淋巴结转移评估中的价值。方法:选取医院收治的100例PTC患者,将其纳入PTC组,同期选取100例甲状腺良性肿瘤患者纳入良性组。两组均采取UE检查,对比两组与有无淋巴结转移PTC患者UE参数(弹性比值、蓝色面积比值),对两组肿瘤组织标本采取CD34免疫组化染色后获取MVD计数,并测定两组肿瘤组织标本中自噬基因[第10号染色体缺失的磷酸酶张力蛋白同源物基因(PTEN)、微管相关蛋白轻链3(PLC3)]、侵袭基因[去整合素-金属蛋白酶9(ADAM9)、BCL6共抑制因子样蛋白1(BCORL1)]以及增殖基因[Xklp2靶蛋白(TPX2)、碱性螺旋-环-螺旋转录因子1(Twist1)]表达量,应用Pearson相关分析探讨PTC的UE参数与MVD计数、自噬、侵袭及增殖有关基因表达的关联性,应用受试者工作特征(ROC)曲线及曲线下面积(AUC)评价UE参数对PTC患者淋巴结转移的诊断价值。结果:PTC组弹性比值、蓝色面积比值均高于良性组(t=8.577,t=5.438;P<0.05),而每个高倍视野中MVD计数低于良性组(t=11.498,P<0.05),肿瘤组织标本中PTEN、LC3mRNA表达量低于良性组,ADAM9、BCORL1、TPX2及Twist1mRNA表达量高于良性组(t=13.587,t=24.321,t=15.139,t=9.537,t=17.437,t=14.978;P<0.05)。PTC患者UE的弹性比值、蓝色面积比值与MVD计数、PTEN、LC3mRNA表达量呈显著负相关(r=-0.599、r=-0.412,r=-0.543,r=-0.520,r=-0.574,r=-0.439;P<0.05),与ADAM9、BCORL1、TPX2及Twist1 mRNA表达量呈显著正相关(r=0.582,r=0.492,r=0.522,r=0.496,r=0.615,r=0.491,r=0.585,r=0.564;P<0.05);有淋巴结转移PTC患者弹性比值、蓝色面积比值高于无淋巴结转移患者(t=6.234,t=2.311;P<0.05);诊断PTC患者淋巴结转移的AUC:弹性比值+蓝色面积比值的AUC为0.883,弹性比值的AUC为0.792,蓝色面积比值的AUC为0.741。结论:UE参数弹性比值、蓝色面积比值与PTC患者肿瘤MVD、癌细胞恶性生物学行为显著相关,并能诊断淋巴结转移,可为临床决策、干预提供重要的参考信息。

Objective:To investigate the correlation between the parameters of ultrasound elastography(UE)of papillary thyroid carcinoma(PTC)and microvessel density(MVD),malignant biological behavior of cancer cells,and its value in the assessment of lymph node metastasis.Methods:100 PTC patients of hospital were selected as the PTC group,100 patients with benign thyroid tumors during the same period were selected as the benign group.Both two groups underwent UE examination,and then the UE parameters(elastic ratio,blue area ratio)were compared between the two groups and patients with or without lymph node metastasis.CD34 immunohistochemical staining was performed on tumor tissue samples from the tumor tissue specimens of two groups to obtain MVD counts.And the expression levels of the autophagy gene[Phosphatase tensin homolog gene(PTEN)deleted on chromosome 10,microtubule-associated protein light chain 3(PLC3)],invasion gene[de-integrin-metal protease 9(ADAM9),BCL6 coinhibitor-like protein 1(BCORL1)],proliferation genes[Xklp2 target protein(TPX2),Twist1]of tumor tissue samples between two groups were determined.Pearson correlation analysis was used to analyze and explore the correlations between UE parameters of PTC and gene expression related to MVD count,autophagy,invasion and proliferation.The receiver operating characteristic(ROC)curve and the area under curve(AUC)were used to evaluate the diagnostic value of UE parameters for lymph node metastasis of PTC patients.Results:The elastic ratio and blue area ratio of PTC group were significantly higher than those of benign group(t=8.577,t=5.438,P<0.05),respectively.The MVD count in each high power field of PTC group was significantly lower than that of benign group(t=11.498,P<0.05).The expression levels of PTEN and LC3 mRNA in tumor tissue specimens of PTC group were significantly lower than that of benign group,and the expression levels of ADAM9,BCORL1,TPX2 and Twist1 mRNA were significantly higher than those of benign group(t=13.587,t=24.321,t=15.139,t=9.537,t=17.437,t=14.978,P<0.05),respectively.The elastic ratio and blue area ratio of UE of PTC patients were significantly negatively correlated with the expression levels of MVD counts,PTEN and LC3 mRNA(r=-0.599,r=-0.412,r=-0.543,r=-0.520,r=-0.574,r=-0.439,P<0.05),and were significantly positively correlated with the expression levels of ADAM9,BCORL1,TPX2 and Twist1 mRNA(r=0.582,r=0.492,r=0.522,r=0.496,r=0.615,r=0.491,r=0.585,r=0.564,P<0.05),respectively.The elastic ratio and blue area ratio of PTC patients with lymph node metastasis were significantly higher than those without lymph node metastasis(t=6.234,t=2.311,P<0.05),respectively.The results of AUCs in diagnosing lymph node metastasis in PTC patients indicated that the AUC of"elastic ratio+blue area ratio"was 0.883,the AUC of elastic ratio was 0.792,and the AUC of blue area ratio was 0.741.Conclusion:The elastic ratio and blue area ratio of UE parameter are significantly correlation with tumor MVD and malignant biological behavior of cancer cell of PTC patients,it can diagnose lymph node metastasis and provide important reference information for clinical decision and intervention.