转移性恶性胸腹腔积液患者肿瘤细胞中乳腺癌易感基因1mRNA的表达与铂类敏感性的关系

Relationship between BRCAI mRNA expression in tumor cells from malignant effusions and chemosensitivity to cisplatin in patients with metastatic malignant effusions

目的研究乳腺癌易感基因1（BRCA1）在转移性恶性胸腹腔积液肿瘤细胞中的表达，并探讨BRCA1基因表达在铂类化疗疗效中的预测作用。方法收集31例经病理确诊的恶性胸腹腔积液标本，分离原代肿瘤细胞。采用细胞计数试剂盒（CCK8）体外药物敏感性试验，检测顺铂（DDP）对原代肿瘤细胞的抗肿瘤作用，采用实时荧光定量PCR法检测肿瘤细胞中BRCA1mRNA的相对表达水平。结果BRCA1mRNA在原代肿瘤细胞中的表达水平为0．618（0．014～18．063），DDP对原代肿瘤细胞的半数抑制浓度（IC50）为2．809μg/ml（0．118～19．439μg/ml）。BRCA1mRNA的表达及DDP对原代肿瘤细胞的IC50值与患者的年龄、性别、原发肿瘤类型、是否接受化疗以及积液类型均无关（均P〉0．05）。BRCA1mRNA的表达水平与DDP抵抗正相关，BRCA1mRNA低表达者对DDP的敏感性高（r=0．786，P〈0．001）。结论检测BRCA1mRNA的表达水平可以为转移性胸腹腔积液患者应用铂类药物化疗提供理论依据。

Objective To explore the mRNA expression of breast cancer susceptibility gene 1 （BRCA1） in tumor cells isolated from malignant pleural and peritoneal effusions, and the predictive role of BRCA1 related to the efficacy of cisplatin-based chemotherapy. Methods Tumor cells were isolated from malignant pleural and peritoneal effusions of 31 cancer patients. The response of these tumor cells to cisplatin was determined by CCK8 assay. Real time quantitative RT-PCR was used to examine the BRCAI mRNA level in the primary culture cancer cells. Results The expression level of BRCA1 mRNA was 0.618 （0. 01±18. 063）in primary culture tumor cells. The IC50 of DDP was 2. 809 μg/ml in the primary culture tumor cells （0. 118-19. 439 μg/ml）. Both BRCA1 mRNA expression and the tumor cells IC50 of DDP were not significantly related with patient age, gender, the type of primary tumor, whether to accept the chemotherapy and effusion type （P 〉0.05）. The level of BRCA1 mRNA was negatively correlated with the chemosensitivity in terms of IC50 of cisplatin （P 〈 0. 001 ）. Conclusion Assessment of expression level of BRCA1 mRNA may be useful in predicting the efficacy of cisp]atin-based chemotherapy in patients with metastatic malignant effusions.