miR-34a is downregulated in cis-diamminedichloroplatinum treated sinonasal squamous cell carcinoma patients with poor prognosis
miR-34a is downregulated in cis-diamminedichloroplatinum treated sinonasal squamous cell carcinoma patients with poor prognosis
复制标题
DOI：
10.1111/j.1349-7006.2012.02338.x
复制
发表时间：
2012-09-01
期刊：
影响因子：
5.7
通讯作者：
Horii, Akira
中科院分区：
文献类型：
--
作者：
Ogawa, Takenori;Saiki, Yuriko;Horii, Akira
为了分析头颈部鳞状细胞癌顺式二胺二氯铂耐药的相关机制，我们分析了RPMI2650及其衍生的先前建立的顺式二胺二氯铂耐药细胞系RPMI2650CR。为了鉴定耐药表型相关的microRNA，我们通过芯片比较了RPMI2650CR和RPMI2650之间的microRNA表达。进一步研究了下调的microrna之一miR-34a。定量逆转录聚合酶链反应证实了miR-34a在RPMI2650CR中的表达降低，但将miR-34a前体导入RPMI2650CR或将miR-34a抑制剂导入RPMI2650并未改变顺式二胺氯铂的敏感性。然而，经动脉内灌注顺式二胺二氯铂治疗的24例鼻窦鳞状细胞癌患者miR-34a表达降低与疾病特异性生存差（P = 0.0015）、无病生存差（P = 0.0019）、局部控制率差（P = 0.017）有显著相关性（中位随访期：53个月）。此外，多因素分析显示，miR-34a表达与无病生存率的风险比为0.005（95%可信区间[CI] 0.000.29, P = 0.011）和局部控制率的风险比为0.008 （95% CI 0.000.44, P = 0.019）之间存在显著相关性，但其他参数如年龄、性别、治疗方法、T和N分期等并未显示出类似的相关性。这些结果强烈提示miR-34a的表达可以成为接受顺式二胺二氯铂治疗的鼻窦鳞状细胞癌患者的独立预后生物标志物。
For the purpose of analyzing mechanisms related to the cis-diamminedichloroplatinum resistance in head and neck squamous cell carcinoma, we analyzed RPMI2650 and its derived previously established cis-diamminedichloroplatinum resistant cell line RPMI2650CR. To identify resistant phenotype-related microRNAs, we compared microRNA expressions between RPMI2650CR and RPMI2650 by microarray. One of the microRNAs as downregulated, miR-34a, was further investigated. Decreased expression of miR-34a in RPMI2650CR was confirmed by quantitative reverse transcription-polymerase chain reaction, but introduction of the miR-34a precursor into RPMI2650CR or the inhibitor of miR-34a into RPMI2650 did not change cis-diamminedichloroplatinum sensitivities. However, 24 patients with sinonasal squamous cell carcinomas treated with intra-arterial infusion of cis-diamminedichloroplatinum showed a significant association between decreased expression of miR-34a and poor disease specific survival (P = 0.0015), poor disease free survival (P = 0.0019), and poor local control rates (P = 0.017) (median follow-up period: 53 months). Furthermore, multivariate analyses demonstrated significant associations between miR-34a expression and the hazard ratios of disease free survival at 0.005 (95% confidence interval [CI] 0.000.29, P = 0.011) and local control rate at 0.008 (95% CI 0.000.44, P = 0.019), although other parameters such as age, gender, treatment method, T and N stages did not show any similar association. These results strongly suggest that miR-34a expression can be an independent prognostic biomarker in patients with sinonasal squamous cell carcinoma who are undergoing treatment with cis-diamminedichloroplatinum.