血清 microRNA 125b 作为接受顺铂为基础的化疗的晚期 NSCLC 患者的诊断或预后生物标志物。
Serum microRNA 125b as a diagnostic or prognostic biomarker for advanced NSCLC patients receiving cisplatin-based chemotherapy.
机构信息
Respiratory Medicine, Huzhou Central Hospital, China.
出版信息
Acta Pharmacol Sin. 2013 Feb;34(2):309-13. doi: 10.1038/aps.2012.125. Epub 2012 Sep 17.
AIM
To investigate the expression profile of microRNAs in inoperable advanced non-small cell lung cancer (NSCLC) patients receiving chemotherapy and the potential relevance of microRNAs to clinicopathological characteristics and prognosis.
METHODS
Serum samples were taken from 260 inoperable advanced NSCLC patients and 260 healthy individuals. All the patients received cisplatin-based chemotherapy, including NP/NC regimens, GP/GC regimens, and TP/TC regimens. The serum levels of microRNAs (miR-125b, miR-10b, miR-34a and miR-155) were determined by quantitative real-time PCR.
RESULTS
Serum levels of the 4 microRNAs examined in NSCLC patients were significantly increased as compared with healthy individuals. The levels of miR-125b and miR-155 were changed in a similar pattern: the patients with stage IV disease had the highest one, while the patients with stage III A and stage III B disease showed similar increased levels. The levels of miR-10b and miR-34a in the patients with different stages were increased to similar extent. The level of miR-125b in poorly differentiated cancer was significantly higher than those in well and moderately differentiated cancers, while the levels of miR-10b, miR-34a, and miR-155 did not significantly differ with cancer differentiation. Among the 4 microRNAs examined, only miR-125b was significantly associated with therapeutic response, exhibiting higher expression levels in non-responsive patients. Furthermore, the high level of miR-125b was significantly correlated with poor patient survival. A multivariate Cox regression analysis showed that the expression level of miR-125b was an independent prognostic marker in NSCLC patients.
CONCLUSION
Our results suggest that miR-125b is a potential diagnostic or prognostic biomarker for NSCLC. This finding has important implications for development of targeted therapeutics to overcome chemotherapeutic resistance in NSCLC.
目的
研究不可手术的晚期非小细胞肺癌（NSCLC）患者化疗后 microRNAs 的表达谱及其与临床病理特征和预后的潜在相关性。
方法
采集 260 例不可手术的晚期 NSCLC 患者和 260 例健康个体的血清样本。所有患者均接受基于顺铂的化疗，包括 NP/NC、GP/GC 和 TP/TC 方案。采用实时定量 PCR 检测 microRNAs（miR-125b、miR-10b、miR-34a 和 miR-155）的血清水平。
结果
与健康个体相比，NSCLC 患者 4 种 microRNAs 的血清水平均显著升高。miR-125b 和 miR-155 的水平变化模式相似：IV 期患者最高，而 IIIA 期和 IIIB 期患者显示相似的升高水平。不同分期患者 miR-10b 和 miR-34a 的水平升高程度相似。低分化癌中 miR-125b 的水平明显高于高分化和中分化癌，而 miR-10b、miR-34a 和 miR-155 的水平与癌症分化程度无显著差异。在检测的 4 种 microRNAs 中，只有 miR-125b 与治疗反应显著相关，无反应患者的表达水平更高。此外，miR-125b 高水平与患者生存不良显著相关。多变量 Cox 回归分析显示，miR-125b 的表达水平是 NSCLC 患者的独立预后标志物。
结论
我们的研究结果表明，miR-125b 是 NSCLC 的潜在诊断或预后生物标志物。这一发现对于开发针对 NSCLC 的靶向治疗以克服化疗耐药性具有重要意义。
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