肺腺癌组织中Connexin 43、TTF-1的表达与CT肺灌注成像的相关性研究

Correlation between the expression of Connexin 43 and TTF-1 and CT lung perfusion imaging in lung adenocarcinoma

目的研究肺腺癌组织中连接蛋白43(Connexin 43)与甲状腺转录因子-1(TTF-1)的表达,并探讨其与CT肺灌注成像的相关性。方法选择2015年1月-2017年12月我院收治的肺腺癌患者148例为研究对象,对患者的肺内单发结节行CT灌注成像,观察血流量(BF)、血容量(BV)与最高增强值(PEI)等灌注参数的变化。运用免疫组化SP法测定Connexin 43、TTF-1在肺腺癌组织及对应的癌旁正常组织中的表达。采用Spearman相关分析探讨Connexin 43、TTF-1表达和患者临床病理特征及灌注参数的关系。结果肺腺癌组织中的Connexin 43表达阳性率为55. 4%,明显低于癌旁正常组织中的Connexin 43表达阳性率100%(P<0. 05)。肺腺癌组织中的TTF-1表达阳性率为81. 8%,明显高于癌旁正常组织中的TTF-1表达阳性率6. 1%(P <0. 05)。Connexin 43表达与肿瘤分化程度、淋巴结转移、p TNM分期均相关(P <0. 05); TTF-1表达与淋巴结转移、p TNM分期均相关(P <0. 05)。148例肺腺癌患者BF为(46. 5±9. 7) m L·100mg-1·min-1,BV为(10. 1±1. 8) m L/100g,PEI为(22. 4±7. 2) HU。相关分析显示,Connexin 43的表达强度与BF、BV均呈负相关(r=-0. 503,P <0. 05; r=-0. 496,P <0. 05),与PEI不相关(r=0. 135,P>0. 05)。TTF-1的表达强度与BF、BV均呈正相关(r=0. 527,P <0. 05; r=0. 481,P <0. 05),与PEI不相关(r=0. 102,P> 0. 05)。Connexin 43表达强阳性组与弱阳性组的BF与BV值均显著低于Connexin 43表达阴性组(P <0. 01)。TTF-1表达强阳性组与弱阳性组的BF与BV值均显著高于TTF-1表达阴性组(P <0. 01)。结论 Connexin 43在肺腺癌组织中阳性表达率较低,而TTF-1蛋白在肺腺癌组织中阳性表达率较高,下调Connexin 43及上调TTF-1蛋白表达与肺腺癌的发生发展密切相关。CT肺灌注成像相关参数值与Connexin 43、TTF-1等肿瘤恶性分子表达水平存在直接相关关系,可将CT灌注成像用于肺腺癌肿瘤分期及治疗效果等方面的评价。

Objective To investigate the expression of connexin 43(Connexin 43)and thyroid transcription factor-1(TTF-1)in lung adenocarcinoma,and to explore their correlation with CT lung perfusion imaging.Methods 148 patients with lung adenocarcinoma treated from January 2015 to 2017 were selected as the subjects.CT perfusion imaging was performed on the solitary pulmonary nodules of the patients.The changes of perfusion parameters such as blood flow(BF),blood volume(BV)and maximum enhancement(PEI)were observed.The expression of Connexin 43 and TTF-1 in lung adenocarcinoma tissues and adjacent normal tissues was detected by immunohistochemical SP.Spearman correlation analysis was used to investigate the relationship between Connexin 43 and TTF-1 expression and clinicopathological features and perfusion parameters.Results The positive rate of Connexin 43 expression in lung adenocarcinoma was 55.4%,which was significantly lower than that in normal tissues adjacent to cancer(Connexin 100%)(100%)(P<0.05).The positive rate of TTF-1 expression in lung adenocarcinoma was 81.8%,which was significantly higher than 6.1% in adjacent normal tissues(P<0.05).The expression of Connexin 43 was correlated with the degree of tumor differentiation,lymph node metastasis and pTNM staging(P<0.05),and the expression of TTF-1 was correlated with lymph node metastasis and pTNM 148 patients with lung adenocarcinoma,BF was(46.5±9.7)ML·100mg-1·Min-1,BV was(10.1±1.8)mL/100g,and PEI was (22.4±7.2)HU.The correlation analysis showed that the expression intensity of Connexin 43 was negatively correlated with BF and BV (r=-0.503,P<0.05;r=-0.496,P<0.05),and was not related to PEI(r=0.135,P>0.05).The expression intensity of TTF-1 was positively correlated with BF and BV (r=0.527,P<0.05;r=0.481,P<0.05),and was not related to PEI(r=0.102,P>0.05).The BF and BV values of Connexin 43 expression in the strong positive group and the weak positive group were significantly lower than those in the negative Connexin 43 expression group(P<0.01).The BF and BV values of TTF-1 expression in the strong positive group and the weak positive group were significantly higher than those in the TTF-1 negative group(P<0.01).Conclusion The positive expression rate of Connexin 43 in lung adenocarcinoma is lower,and the positive expression rate of TTF-1 protein in lung adenocarcinoma is higher.The down-regulation of Connexin 43 and the up-regulation of TTF-1 protein are closely related to the development of lung adenocarcinoma.There is a direct correlation between the parameters of CT pulmonary perfusion imaging and the expression level of malignant molecules such as Connexin 43 and TTF-1.CT perfusion imaging can be used to evaluate the stage and therapeutic effect of lung adenocarcinoma.