动态增强磁共振成像评价新辅助化疗术对乳腺癌血管生成及细胞增殖的影响

The effects of neoadjuvant chemotherapy on angiogenesis and cell proliferation of breast cancer in the DCEMRI evaluation

目的:探讨动态增强磁共振成像(DCE-MRI)在评价新辅助化疗术对乳腺癌血管生成及细胞增殖的影响中的价值。方法:选择医院收治并经组织病理学检查确诊的92例乳腺癌患者,于患者治疗前、治疗后28 d行DCE-MRI检查,并获得容量转运常数(K^(trans))、速率常数(K_(ep))及血管外细胞外间隙容积常数(Ve)等定量参数。依据治疗效果将患者分为完全有效(CR)组(21例),部分有效(PR)组(58例)和无效(NR)组(13例),比较不同疗效患者的DCE-MRI参数、病灶组织中血管新生基因、细胞增殖基因mRNA表达量的差异,采用Pearson检验分析新辅助化疗术后对乳腺癌DCE-MRI参数与血管新生及细胞增殖间的关系。结果:治疗后,不同疗效组的K^(trans)、K_(ep)的差异有统计学意义(F=27.410,F=20.386;P<0.05);NR组的血管新生基因、细胞增殖基因mRNA表达量Cyr61、HIF-1α、VEGF和MMP-9基因的mRNA表达量高于CR组、PR组,差异有统计学意义(F=12.184,F=15.933,F=13.267,F=11.682;P<0.05);新辅助化疗后DCE-MRI参数K^(trans)、K_(ep)对疗效具有预测价值(F=27.410,F=20.386;P<0.05);Pearson检验结果显示,K^(trans)、K_(ep)与血管新生基因、细胞增殖基因(除Kiss-1外)mRNA表达量呈正相关(r_(Cyr61)=0.705,r_(HIF-α)=0.689,r_(VEGF)=0.721,r_(MMP-9)=0.637,r_(CXCR7)=0.593,r_(SphKl)=0.724,r_(EZH2)=0.705,r_(IFT57)=0.705;P<0.05),与Kiss-1基因的mRNA表达量呈负相关(r=-0.713,r=-0.700;P<0.05)。结论:DCE-MRI参数K^(trans)、K_(ep)可有效判断新辅助化疗术治疗乳腺癌的疗效,其与乳腺癌血管新生及细胞增殖存在明显相关性。

Objective:To explore the value of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)in evaluating the effects of neoadjuvant chemotherapy on angiogenesis and cell proliferation in breast cancer.Methods:92 patients with breast cancer who admitted to hospital and were confirmed by histological examination were selected.DCE-MRI examination was implemented on patients before they received treatment,and at 28th d after they received treatment.And a series of quantitative parameters included volume transfer constant(K^(trans)),rate constant(K_(ep))and extravascular and extracellular space volume constant(Ve)were obtained.Patients were divided into complete response(CR)group(21 cases),partial response(PR)group(58 cases)and non-response(NR)group(13 cases)according to the therapeutic effects.The differences of DCE-MRI parameters,the mRNA expression quantities of angiogenesis gene and cell proliferation gene in the focus tissue among patients with different therapeutic effects were compared.Pearson test was used to analyze the relationships between DCE-MRI parameters and angiogenesis,and between that and cell proliferation after the treatment with neoadjuvant chemotherapy for breast cancer.Results:There were significant differences in K^(trans)and K_(ep)between different groups after treatment(F=27.410,F=20.386,P<0.05).And the mRNA expression levels of angiogenesis gene and cell proliferation gene(Cyr61,HIF-1α,VEGF and MMP-9)of NR group were significantly higher than those of CR group and PR group(F=12.184,F=15.933,F=13.267,F=11.682,P<0.05).The K^(trans)and K_(ep)of DCE-MRI parameters after neoadjuvant chemotherapy had predictive value to the curative effect(F=27.410,F=20.386,P<0.05).The results of Pearson test showed that K^(trans)and K_(ep)were positively correlated with the mRNA expression levels of angiogenesis gene and cell proliferation gene(except Kiss-1)(r_(Cyr61)=0.705,r_(HIF-α)=0.689,r_(VEGF)=0.721,r_(MMP-9)=0.637,r_(CXCR7)=0.593,r_(SphKl)=0.724,r_(EZH2)=0.705,r_(IFT57)=0.705,P<0.05),and were negatively correlated with the mRNA expression level of Kiss-1 gene(r=-0.713,r=-0.700,P<0.05).Conclusion:K^(trans)and K_(ep)of DCE-MRI parameters can effectively judge the curative effect of neoadjuvant chemotherapy in treating breast cancer,and they are significantly correlated with angiogenesis and cell proliferation of breast cancer.