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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >Candidate MicroRNA Biomarkers of Therapeutic Response to Sunitinib in Metastatic Renal Cell Carcinoma: A Validation Study in Patients with Extremely Good and Poor Response
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Candidate MicroRNA Biomarkers of Therapeutic Response to Sunitinib in Metastatic Renal Cell Carcinoma: A Validation Study in Patients with Extremely Good and Poor Response

机译：候选MicroRNA生物标志物的转移性肾细胞癌的孙氨醇：患者患者患者极其良好，差

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Background/Aim: Targeted therapy with the tyrosine kinase inhibitor sunitinib is used in the first line of metastatic renal cell carcinoma (mRCC) treatment. The aim of the present study was independent validation of microRNAs (miRNAs) identified in previous studies as biomarkers predicting response to sunitinib therapy. Materials and Methods: Based on a literature search, 10 miRNAs were chosen from six relevant studies as candidates for validation: miR-155, miR-484, miR-221, miR-222 , miR-425 , miR-133, miR-410, miR-141, miR-628 and miR-942. Validation of these miRNAs was performed on cohort of 56 patients with mRCC with extremely good or poor response responses to sunitinib treatment using quantitative reverse transcription-polymerase chain reaction. Patients were divided into either responding (n=24) or non-responding (n=32) groups to sunitinib treatment according to Response Evaluation Criteria in Solid Tumors and progression free survival (PFS). All patients in the responding group had PFS longer than 18 months, PFS of non-responders was shorter than 6 months in all cases. Results: miR-942 and miR-133 were confirmed as being differentially expressed in tumors of responding and non-responding patients. It was not possible to validate the predictive value of other tested miRNAs, however, expression of miR-221 and miR-425 tended to be positively associated with therapeutic response (p0.1). We further developed a model based on the combination of miR-942 and miR-133 expression, that enabled identification of non-responding patients with mRCC with sensitivity of 78% and specificity of 79% (area under the curve=0.8071). Conclusion: Following further independent validation, detection of these miRNAs may prevent unnecessary and costly approaches to therapy in non-responding patients with mRCC.
机译：背景/目的：靶向治疗与酪氨酸激酶抑制剂Sunitinib在第一线转移肾细胞癌（MRCC）治疗中使用。本研究的目的是在先前研究中确定的微小RNA（miRNA）的独立验证，作为预测孙炎治疗的反应的生物标志物。材料和方法：基于文献搜索，从六个相关研究中选择10名MIRNA作为验证候选者：MIR-155，MIR-484，MIR-221，MIR-222，MIR-425，MIR-133，MIR-410 ，miR-141，miR-628和miR-942。使用定量逆转录 - 聚合酶链反应对56例MRCC的56名患者的群体进行56例MRCC的患者的核心进行验证。根据实体肿瘤的响应评估标准和进展免费存活（PFS），将患者分为响应（n = 24）或不响应（n = 32）组到孙氨基治疗。响应组中所有患者的患者均超过18个月，非响应者的PFS在所有情况下短于6个月。结果：MiR-942和MIR-133被证实在响应和无应答患者的肿瘤中差异表达。然而，不可能验证其他测试的miRNA的预测值，然而，miR-221和miR-425的表达往往与治疗响应呈正相关（p <0.1）。我们进一步开发了基于miR-942和miR-133表达的组合的模型，使得能够鉴定患有MRCC的无响应患者，敏感性为78％，特异性为79％（曲线下的面积= 0.8071）。结论：在进一步独立的验证之后，这些miRNA的检测可以防止不必要的且昂贵的患者在非答复患者中治疗MRCC。

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