MicroRNA 92a-2 A Biomarker Predictive for Chemoresistance and Prognostic for Survival in Patients with Small Cell Lung Cancer
MicroRNA 92a-2 A Biomarker Predictive for Chemoresistance and Prognostic for Survival in Patients with Small Cell Lung Cancer
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DOI：
10.1097/jto.0b013e3181dea6be
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发表时间：
2010-08-01
影响因子：
20.4
通讯作者：
Weiss, Glen J.
中科院分区：
文献类型：
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作者：
Ranade, Aarati R.;Cherba, David;Weiss, Glen J.
目的：尽管大多数小细胞肺癌（SCLC）患者对初始化疗有反应，但在首次反应评估（化疗耐药）时疾病进展的患者预后较差。需要预测性生物标志物来帮助研究人员设计未来的临床试验，以便在标准临床和实验室参数之外更好地对患者进行分层，并确定针对该患者亚群的新治疗方法。我们假设肿瘤microRNAs （miRNAs）可以作为SCLC全身化疗患者化疗耐药的预测性生物标志物和生存预后生物标志物。患者和方法：有临床特征和基线合并症注释的SCLC样本是可用的。对诊断性SCLC肿瘤样本进行miRNA微阵列分析，并使用XenoBase（数据集成和发现工具）进行分析。通过定量实时聚合酶链反应确定前16个候选miRNA，然后进行分析，确定与化疗耐药和生存相关的临床和miRNA生物标志物。结果：miR-92a-2* (p = 0.010)、miR- 147 （p = 0.018）和miR574-5p （p = 0.039）与化疗耐药显著相关。通过逐步多因素分析，只有性别和miR-92a-2*对生存率有显著影响（p = 0.023）和（p = 0.015）。基线合并症与化疗耐药或生存率无关。结论：较高的肿瘤miR-92a-2*水平与SCLC患者的化疗耐药和生存率降低有关。肿瘤miR-92a-2*可能应用于筛选有新发化疗耐药风险的SCLC患者，以便为这一亚群设计更有针对性的临床试验。在独立样本集中进一步验证是必要的。
Purpose: Although the majority of patients with small cell lung cancer (SCLC) respond to initial chemotherapy, those with disease progression at first response assessment (chemoresistance) have inferior outcomes. There is a need for predictive biomarkers to aid investigators in designing future clinical trials that better stratify patients beyond standard clinical and laboratory parameters and to identify new treatments for this patient subpopulation. We hypothesized that tumor microRNAs (miRNAs) could serve as predictive biomarkers for chemoresistance and prognostic biomarkers for survival of patients with SCLC treated with systemic chemotherapy.Patients and Methods: SCLC samples annotated with clinical characteristics and baseline comorbidities were available. miRNA microarray profiling was performed on diagnostic SCLC tumor samples, and analysis was performed using XenoBase, a data integration and discovery tool. Confirmation of the top 16 miRNA candidates was performed using quantitative real-time polymerase chain reaction followed by analyses to determine clinical and miRNA biomarkers associated with chemoresistance and survival.Results: miRNAs significantly associated with chemoresistance were miR-92a-2* (p = 0.010), miR- 147 (p = 0.018), and miR574-5p (p = 0.039). By stepwise multivariate analysis, only gender and miR-92a-2* contributed significantly to survival (p = 0.023) and (p = 0.015), respectively. Baseline comorbidities were not associated with chemoresistance or survival.Conclusions: Higher tumor miR-92a-2* levels are associated with chemoresistance and with decreased survival in patients with SCLC. Tumor miR-92a-2* may have application in screening patients with SCLC at risk for de novo chemoresistance in an effort to design more tailored clinical trials for this subpopulation. Further validation in independent sample sets is warranted.