Clinical Cancer Research文章：miRNA的表達與肺鱗癌的診斷與預后

　　世界上每年有超過160萬例肺癌新發(fā)病例，超過137萬人死于肺癌。中國每年有52萬例肺癌新發(fā)病例，超過45萬人死于肺癌。80%肺癌是非小細胞肺癌，非小細胞肺癌中40%是鱗癌。ⅠA期肺鱗癌患者的5年存活率約為60%，而Ⅱ-Ⅳ期肺鱗癌患者的5年存活率為5% - 40%。因此，發(fā)現(xiàn)新的標志物并應用于早期診斷和預后對于提高肺鱗癌患者的生存率具有重要意義。

　　中國醫(yī)學科學院腫瘤研究所赫捷教授與清華大學郭永副研究員合作利用microRNA芯片系統(tǒng)的比較了60對肺鱗癌和癌旁組織microRNA表達譜的差異，發(fā)現(xiàn)了一個包含5個microRNA的分類器（hsa-miR-210, hsa-miR-182, hsa-miR-486-5p, hsa-miR-30a and hsa-miR-140-3p)。該分類器區(qū)分肺鱗癌和正常肺組織的準確率超過94%。與此同時，他們還發(fā)現(xiàn)hsa-miR-31的表達量與病人的存活期負相關。DICER1基因是hsa-miR-31的靶基因。

　　上述研究的博奧生物晶芯®哺乳動物miRNA芯片服務與Real time RT-PCR服務在博奧生物有限公司完成。

原文摘要：

　　A 5-MicroRNA Signature for Lung Squamous Cell Carcinoma Diagnosis and hsa-miR-31 for Prognosis
　　Purpose: Recent studies have suggested that microRNA biomarkers could be useful for stratifying lung cancer subtypes, but microRNA signatures varied between different populations. Squamous cell carcinoma (SCC) is one major subtype of lung cancer that urgently needs biomarkers to aid patient management. Here, we undertook the first comprehensive investigation on microRNA in Chinese SCC patients.
Experimental Design: MicroRNA expression was measured in cancerous and noncancerous tissue pairs strictly collected from Chinese SCC patients (stages I–III), who had not been treated with chemotherapy or radiotherapy prior to surgery. The molecular targets of proposed microRNA were further examined.

　　Results: We identified a 5-microRNA classifier (hsa-miR-210, hsa-miR-182, hsa-miR-486-5p, hsa-miR-30a, and hsa-miR-140-3p) that could distinguish SCC from normal lung tissues. The classifier had an accuracy of 94.1% in a training cohort (34 patients) and 96.2% in a test cohort (26 patients). We also showed that high expression of hsa-miR-31 was associated with poor survival in these 60 SCC patients by Kaplan–Meier analysis (P = 0.007), by univariate Cox analysis (P = 0.011), and by multivariate Cox analysis (P = 0.011). This association was independently validated in a separate cohort of 88 SCC patients (P = 0.008, 0.011, and 0.003 in Kaplan–Meier analysis, univariate Cox analysis, and multivariate Cox analysis, respectively). We then determined that the tumor suppressor DICER1 is a target of hsa-miR-31. Expression of hsa-miR-31 in a human lung cancer cell line repressed DICER1 activity but not PPP2R2A or LATS2.

　　Conclusions: Our results identified a new diagnostic microRNA classifier for SCC among Chinese patients and a new prognostic biomarker, hsa-miR-31.

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