miRNA的表达与肺鳞癌的诊断与预后
世界上每年有超过160万例肺癌新发病例，超过137万人死于肺癌。中国每年有52万例肺癌新发病例，超过45万人死于肺癌。80%肺癌是非小细胞肺癌，非小细胞肺癌中40%是鳞癌。ⅠA期肺鳞癌患者的5年存活率约为60%，而Ⅱ-Ⅳ期肺鳞癌患者的5年存活率为5% - 40%。因此，发现新的标志物并应用于早期诊断和预后对于提高肺鳞癌患者的生存率具有重要意义。
中国医学科学院肿瘤研究所赫捷教授与清华大学郭永副研究员合作利用microRNA芯片系统的比较了60对肺鳞癌和癌旁组织microRNA表达谱的差异，发现了一个包含5个microRNA的分类器（hsa-miR-210, hsa-miR-182, hsa-miR-486-5p, hsa-miR-30a and hsa-miR-140-3p)。该分类器区分肺鳞癌和正常肺组织的准确率超过94%。与此同时，他们还发现hsa-miR-31的表达量与病人的存活期负相关。DICER1基因是hsa-miR-31的靶基因。
上述研究的博奥生物晶芯®哺乳动物miRNA芯片服务与Real time RT-PCR服务在博奥生物有限公司完成。
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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