Hu An, Huang Jing-Juan, Xu Wei-Hua, Jin Xiao-Jie, Li Ji-Ping, Tang Yuan-Jia, Huang Xin-Fang, Cui Hui-Juan, Sun Guang-Bin, Li Rui-Lin, Duan Jun-Li
Department of Otolaryngology, Gongli Hospital Pudong New Area, Miaopu Road 219, Shanghai 200135, China.
Department of Gerontology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine Kongjiang Road 1665, Shanghai 200092, China.
Am J Cancer Res. 2015 Apr 15;5(5):1775-85. eCollection 2015.
We sought to identify microRNAs that exhibit altered expression in laryngeal squamous cell carcinoma (SCC) and to determine whether microRNA expression is predictive of disease. This study was divided into three steps: (1) The expression of six miRNAs, such as up-regulated miR-223, miR-142-3p, miR-21, miR-16, miR-23a and down-regulated miR-375, was evaluated using total RNA isolated from freshly-frozen primary tumors and non-cancerous laryngeal squamous epithelial tissues and analyzed using quantitative real-time polymerase chain reaction (qRT-PCR). (2) We also investigated the mRNA expression levels of processing elements (RNASEN, DGCR8, and DICER1) that participate in miRNA-biogenesis pathway. (3) We analyzed the relationships between the expression levels of these miRNAs and the clinicopathologic parameters of laryngeal SCC patients. In this study, we found that: (1) A marked difference in the microRNA expression pattern was observed between tumors and non-cancerous tissue. With regard to miRNA-processing elements, the expression level of RNASEN was higher in laryngeal SCC than in normal epithelium (P<0.01). (2) The miR-21/miR-375 expression ratio was highly sensitive and specific for disease prediction. Kaplan-Meier analysis revealed a significant association between high expression of miR-21/miR-375 in cancerous tissue and a worse prognosis (p=0.032). (3) Furthermore, the expression ratio of miR-21/mir-375 in patients with stage (III-IV) tumors was significantly higher than that in those with stage (I-II) tumors (p=0.006). These data suggest that the pattern of microRNA expression in primary laryngeal SCC tissues is exhibiting strong predictive potential.
我们试图鉴定在喉鳞状细胞癌(SCC)中表达发生改变的微小RNA,并确定微小RNA表达是否可预测疾病。本研究分为三个步骤:(1)使用从新鲜冷冻的原发性肿瘤和非癌性喉鳞状上皮组织中分离的总RNA,评估六种微小RNA的表达,如上调的miR-223、miR-142-3p、miR-21、miR-16、miR-23a和下调的miR-375,并使用定量实时聚合酶链反应(qRT-PCR)进行分析。(2)我们还研究了参与微小RNA生物合成途径的加工元件(RNASEN、DGCR8和DICER1)的mRNA表达水平。(3)我们分析了这些微小RNA的表达水平与喉SCC患者临床病理参数之间的关系。在本研究中,我们发现:(1)在肿瘤组织和非癌组织之间观察到微小RNA表达模式存在显著差异。关于微小RNA加工元件,喉SCC中RNASEN的表达水平高于正常上皮(P<0.01)。(2)miR-21/miR-375表达比值对疾病预测具有高度敏感性和特异性。Kaplan-Meier分析显示,癌组织中miR-21/miR-375高表达与较差的预后显著相关(p=0.032)。(3)此外,III-IV期肿瘤患者的miR-21/mir-375表达比值显著高于I-II期肿瘤患者(p=0.006)。这些数据表明,原发性喉SCC组织中的微小RNA表达模式具有很强的预测潜力。