CYP3A4、CYP3A5在肺腺癌中表达及其与预后的相关性

Relationship between the expressions of CYP3A4,CYP3A5 and prognosis in lung adenocarcinoma

目的探讨CYP3A4、CYP3A5在肺腺癌组织中的表达水平及与预后的相关性。方法收集南京医科大学附属肿瘤医院胸外科87例肺腺癌病理组织及其对应的临床资料,病理标本制作组织芯片,通过免疫组化法明确组织芯片中CYP3A4、CYP3A5蛋白的表达情况,结合临床病理特征和随访资料进行统计分析。结果肺腺癌组织芯片的免疫组化结果显示,CYP3A4在肺腺癌组织中显著高表达,而其在癌旁正常组织中则显著低表达(P=0.012);肺腺癌中CYP3A4的表达水平与肺腺癌TMN分期(P=0.013)和肿瘤分化程度(P=0.044)相关。与之相反,CYP3A5在肺腺癌组织中的表达水平显著低于癌旁正常组织(P<0.001);肺腺癌中CYP3A5的表达与肺腺癌组织分化程度(P=0.013)显著相关。CYP3A4高表达患者总生存期和无瘤生存期较CYP3A4低表达患者显著缩短(P<0.05),CYP3A5低表达患者总体生存期和无瘤生存期较CYP3A5高表达患者显著缩短(P<0.05);联合分析显示,CYP3A4高表达合并CYP3A5低表达的患者预后较其他患者差(P<0.05),COX多因素分析显示,CYP3A4高表达合并CYP3A5低表达为肺腺癌预后不良的独立危险因素。结论 CYP3A4高表达合并CYP3A5低表达是影响肺腺癌患者预后的独立危险因素;CYP3A4高表达合并CYP3A5低表达可作为预测肺腺癌预后的一个新靶标。

Objective To investigate the expression of CYP3A4 and CYP3A5 in lung adenocarcinoma and its correlation with prognosis. Methods The clinical features of 87 lung adenocarcinoma patients were col- lected. Subsequently, immunohistochemical （IHC） analysis was performed to detect CYP3A4 and CYP3A5 ex- pressions in 87 lung adenocarcinoma cases on a tissue microarray sample. Finally, the relationship between CYP3A4 and CYP3A5 expression as well as the clinic pathological characteristics of NSCLC were analyzed sta- tistically. Results Our study showed that the expression of CYP3A4 was significantly higher in lung adenocar- cinoma than that in normal tumor-adjacent tissues （P = 0. 012）. CYP3A4 protein expression in lung adenocarci- noma was related to TNM stage （ P = 0. 013 ） and differentiation （ P = 0. 044 ）. Expression of CYP3A5 was lower in lung adenocarcinoma than that in normal-adjacent tissues （ P 〈 0. 05 ）. Significance was observed between CYP3A5 expression and differentiation （P = 0. 013 ）. The Kaplan-Meier method suggested that high CYP3A4 and low CYP3A5 expressions were significantly associated with short disease-free survival and overall survival of patients. Conclusions This study provides evidence that the high CYP3A4 and low CYP3A5 expression level was an independent risk factor of lung adenocarcinoma and could act as a new target for prognosis of lung adeno- carcinoma.