Clin Cancer Res 2011 Nov;17 (21): 6802-11. [IF:7.338]
A 5-MicroRNA Signature for Lung Squamous Cell Carcinoma Diagnosis and hsa-miR-31 for Prognosis.
Tan X , Qin W , Zhang L , Hang J , Li B , Zhang C , Wan J , Zhou F , Shao K , Sun Y , Wu J , Zhang X , Qiu B , Li N , Shi S , Feng X , Zhao S , Wang Z , Zhao X , Chen Z , Mitchelson K , Cheng J , Guo Y , He J .
Authors' Affiliations: Departments of Thoracic Surgery and Pathology, Cancer Hospital and Institute, Peking Union Medical College and Chinese Academy of Medical Sciences; Medical Systems Biology Research Center, Department of Biomedical Engineering, and The State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University; National Engineering Research Center for Beijing Biochip Technology; and CapitalBio Corporation, Beijing, P.R. China.
中国医学科学院，清华大学医学系统生物学研究中心，清华大学生物膜与膜生物工程国家重点实验室，生物芯片北京国家工程研究中心
Abstract
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. 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. 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. Our results identified a new diagnostic microRNA classifier for SCC among Chinese patients and a new prognostic biomarker, hsa-miR-31. Clin Cancer Res; 17(21); 6802-11. 2011 AACR.
摘要：
最近研究表明microRNA生物标记可以用于肺癌的分型，但是microRNA在不同人群中表达是不同的。鳞癌是肺癌的一个主要亚型，亟待使用生物探针去协助治疗。因此，我们首次对中国肺鳞癌患者进行了庞大的microRNA研究。
我们检测了来自中国的肺鳞癌病人（I—III期）肿瘤组织及相应的非肿瘤组织中microRNA的表达情况，这些病人在手术之前未接受过化疗或者是放疗。同时也进行了针对microRNA的靶向研究。我们鉴定出含有5种microRNA的试剂盒（hsa-miR-210, hsa-miR-182, hsa-miR-486-5p, hsa-miR-30a, and hsa-miR-140-3p），它能够把肺鳞癌从正常肺组织中鉴别出来。该试剂盒在training 组（34例）和试验组（26例）的灵敏度分别为94.1%和96.2%。
我们通过Kaplan-Meier分析 (P = 0.007), Cox比例风险模型单因素分析 (P = 0.011)和Cox多因素分析(P = 0.011)发现在这60个病人中高表达hsa-miR-31预后较差。这种联系在另一组88个肺鳞癌中得到了验证（其Kaplan-Meier分析、 Cox比例风险模型单因素分析、多因素分析分别为P = 0.008, 0.011, and 0.003）。
所以我们认为抑瘤基因DICER1是hsa-miR-31的目的基因，肺癌细胞中表达hsa-miR-31可以抑制DICER1活性，而不是PPP2R2A 或LATS2。我们的研究鉴定出一个新的针对中国肺癌病人的诊断性的microRNA试剂盒和一个新的预后生物标记物hsa-miR-31。
