目的分析恶性胸腹腔积液中原代肿瘤细胞胸苷酸合成酶(TS)基因的mRNA表达水平,探讨TS基因在恶性胸腹腔积液患者中对培美曲塞药物化疗疗效的预测作用。方法收集39例经病理确诊的Ⅳ期恶性肿瘤患者的恶性胸腹腔积液,分离原代肿瘤细胞,采用ATP-TCA法体外药物敏感试验检测化疗药物对原代肿瘤细胞的抗肿瘤作用;提取原代肿瘤细胞的总RNA,采用实时荧光定量PCR方法检测原代肿瘤细胞中培美曲塞药物疗效相关基因TS的相对表达水平。结果在恶性胸腹腔积液中,原代肿瘤细胞中TS mRNA的相对表达水平与恶性肿瘤患者的临床特征无明显相关性(P〉0.05);TS mRNA表达水平与培美曲塞药敏结果呈负相关,TS低表达,培美曲塞更敏感(P〈0.05)。结论恶性胸腹腔积液中原代肿瘤细胞TS mRNA的表达水平与培美曲塞体外药物敏感性相关。对于有恶性胸腹腔积液患者,可通过简单的胸腹腔穿刺获得与化疗药物疗效相关的基因信息,从而为恶性胸腹腔积液患者实施个体化治疗提供理论基础。
Objective To explore the mRNA expression of thymidylate synthase( TS) in tumor cells isolated from malignant pleural and peritoneal effusions,and to investigate the predictive role of TS to the efficacy of pemetrexed-based chemotherapy. Methods Tumor cells were isolated from malignant pleural and peritoneal effusions of 39 patients with malignant tumor. Viable tumor cells were tested for sensitivity to pemetrexed using ATP-TCA assay. RT-PCR was used to examine the TS mRNA level in the primary cultured cancer cells. Results The expression level of TS mRNA in malignant effusions was negatively correlated with pemetrexed sensitivity. The expression of TS mRNA was not related to age,gender or tumor type. Conclusions The results indicate that the expression level of TS mRNA in malignant effusions is negatively correlated with sensitivity to pemetrexed. Chest or abdominal puncture may play an important role for"real-time"individualized chemotherapy while tumor progression.