Micro-RNA profiles in osteosarcoma as a predictive tool for ifosfamide response
Micro-RNA profiles in osteosarcoma as a predictive tool for ifosfamide response
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DOI：
10.1002/ijc.25715
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发表时间：
2011-08-01
影响因子：
6.4
通讯作者：
Alberti, Laurent
中科院分区：
文献类型：
--
作者：
Gougelet, Angelique;Pissaloux, Daniel;Alberti, Laurent
Micro-RNA (miRNA) 目前被用作血液癌症和实体瘤的癌症生物标志物。骨肉瘤是第一种原发性恶性骨肿瘤，其特征是复杂的遗传和对常规治疗的抵抗。对于后一种特性，尽管术前给予了化疗药物，但自 1990 年以来中位生存率并未得到改善。化疗前对肿瘤反应的预测将构成这一病理学的重大进展。我们在这项研究中评估了 miRNA 分析是否可以超越目前骨肉瘤诊断的局限性。我们测量了不同骨肉瘤样本中的 miRNA 表达：(i) 27 个来自患者的骨肉瘤石蜡包埋肿瘤，(ii) 人骨肉瘤细胞系，以及 (iii) 来自同基因大鼠骨肉瘤模型的肿瘤，再现了人骨肉瘤。使用微流控卡确定 miRNA 谱，微流控卡执行基于 TaqMan (R) 的高通量 PCR 测定，称为 TaqMan (R) 低密度阵列。大鼠和人类来源的骨肉瘤显示出 miRNA 特征，可以区分良好的反应者和不良的反应者。特别是，我们在患者肿瘤中鉴定出了 5 个有区别的 miRNA（miR-92a、miR-99b、miR-132、miR-193a-5p 和 miR-422a），这些 miRNA 可以很容易地用于诊断。这些有区别的 miRNA 以及在大鼠中鉴定的 miRNA 均针对 TGF beta、Wnt 和 MAP 激酶通路。这些结果表明，我们的平台构成了一种有效的诊断工具，可以预测肿瘤对药物的敏感性，以尝试更好地适应肿瘤生物学特异性的治疗，并确定新的潜在治疗策略。
Micro-RNAs (miRNA) are currently used as cancer biomarkers for hematological cancers and solid tumors. Osteosarcoma is the first primary malignant bone tumor, characterized by a complex genetic and resistance to conventional treatments. For this latter property, the median survival has not been improved since 1990 despite preoperative administration of chemotherapeutic agents. The prediction of tumor response before chemotherapy treatment would constitute a major progress for this pathology. We assessed in this study if miRNA profiling could surpass the current limitations for osteosarcoma diagnosis. We measured the miRNA expression in different osteosarcoma samples: (i) 27 osteosarcoma paraffin-embedded tumors from patients, (ii) human osteosarcoma cell lines, and (iii) tumors from a syngeneic rat osteosarcoma model, recapitulating human osteosarcoma. miRNA profiles were determined using microfluidic cards performing high-throughput TaqMan (R)-based PCR assays, called TaqMan (R) Low Density Arrays. Osteosarcoma of rat and human origins showed a miRNA signature, which could discriminate good from bad responders. In particular, we identified five discriminating miRNAs (miR-92a, miR-99b, miR-132, miR-193a-5p and miR-422a) in patient tumors, which could be easily transferable to diagnosis. These discriminating miRNAs, as well as those identified in rat, targeted the TGF beta, the Wnt and the MAP kinase pathways. These results indicate that our platform constitutes a potent diagnostic tool to predict tumor sensitivity to a drug in attempt to better adapt treatment to tumor biological specificities and also to identify new potential therapeutic strategies.