Laboratory of Genetic Toxicology, National Institute of Pediatrics, Mexico City, Mexico.
Department of Pediatric Oncology, National Institute of Pediatrics, Mexico City, Mexico.
Cancer Biomark. 2018;22(2):317-324. doi: 10.3233/CBM-171027.
Intratumoral up-regulation of genes coding for drug transporters and metabolizing enzymes, such as MDR1 and CYP3A4, after chemotherapy are linked to cancer drug resistance. However their expression in primary soft tissue sarcomas (STS) prior to drug treatment and their role in innate resistance remain unclear.
The aim of this study was characterize MDR1 and CYP3A4 expression pattern before to chemotherapy and its clinical implication in pediatric STS.
In this prospective study we analyzed MDR1 and CYP3A4 mRNA expression in both normal and tumor tissues from 28 newly diagnosed STS pediatric and then compared with patients' clinical-pathological data, including chemotherapy response.
Our data showed that the expression of the MDR1 gene was significantly higher in malignant tissue than in the normal tissues of patients with STS. In addition, high MDR1 expression was significantly associated with local advances, as well as poor response to treatment. In contrast, CYP3A4 expression level was negligible in both tumoral and non-tumoral tissues.
These results suggest that a significant mRNA level of MDR1 gene was intrinsically present in STS before exposure to chemotherapeutic drugs, suggesting that MDR1 may be important contributors of innate chemoresistance of this tumor type.
化疗后肿瘤内编码药物转运蛋白和代谢酶的基因（如 MDR1 和 CYP3A4）的上调与癌症药物耐药性有关。然而，它们在原发性软组织肉瘤（STS）中的表达在药物治疗之前以及它们在固有耐药性中的作用尚不清楚。
本研究旨在描述化疗前 MDR1 和 CYP3A4 的表达模式及其在儿科 STS 中的临床意义。
在这项前瞻性研究中，我们分析了 28 例新诊断的 STS 儿科患者的正常和肿瘤组织中的 MDR1 和 CYP3A4 mRNA 表达，并将其与患者的临床病理数据进行比较，包括化疗反应。
我们的数据表明，MDR1 基因的表达在 STS 患者的恶性组织中明显高于正常组织。此外，高 MDR1 表达与局部进展以及对治疗的不良反应显著相关。相比之下，CYP3A4 在肿瘤和非肿瘤组织中的表达水平可以忽略不计。
这些结果表明，MDR1 基因的 mRNA 水平在 STS 暴露于化疗药物之前就已经显著存在，表明 MDR1 可能是这种肿瘤类型固有化疗耐药性的重要贡献者。
