MicroRNA expression ratio is predictive of head and neck squamous cell carcinoma.
MicroRNA expression ratio is predictive of head and neck squamous cell carcinoma.
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DOI：
10.1158/1078-0432.ccr-08-3131
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发表时间：
2009-04-15
期刊：
影响因子：
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通讯作者：
Marsit CJ
中科院分区：
文献类型：
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作者：
Avissar M;Christensen BC;Kelsey KT;Marsit CJ
这项工作已经证明，microRNA表达率可以在头颈部鳞状细胞癌（HNSCC）的背景下非常准确地区分非病变组织和肿瘤组织，头颈部鳞状细胞癌是全球重要的公共卫生问题。miR-221：miR-375的比值显示出较高的区分潜力，在区分肿瘤与正常组织方面具有92%的灵敏度和93%的特异性，并且表明这种简单的分子标记物可能具有作为诊断工具的显著临床潜力。microRNA（miRNAs）参与癌症及其作为诊断和预后生物标志物的潜力正日益受到重视。我们试图鉴定头颈部鳞状细胞癌（HNSCC）中改变的miRNA，并确定miRNA表达是否是疾病的预测因子。通过微阵列分析从新鲜冷冻的原发性肿瘤、新鲜冷冻的未患病的头颈部上皮组织和HNSCC细胞系分离的RNA的662个miRNA的表达。随后使用总共99个HNSCC样品和14个正常上皮细胞通过qRT-PCR验证在阵列上和通过qRT-PCR差异表达的miRNA。在肿瘤和细胞系之间观察到miRNA表达模式的显著差异。18个miRNAs在正常组织和肿瘤组织中的表达发生了显著变化。这些miRNAs中的4个在较大的样本系列中得到验证，并且每个都显示出显著的差异表达（P < 0.0001）。此外，miR-221：miR-375的表达比率证明了用于疾病预测的高灵敏度（0.92）和特异性（0.93）。这些数据表明，培养的肿瘤细胞系不适合用于miRNA生物标志物鉴定，并且原发性头颈组织中miRNA表达的模式反映了疾病状态，某些miRNA表现出很强的预测潜力。这些结果表明，miR-221和miR-375应作为诊断生物标志物进行进一步评估，因为它们可能在定义广泛响应的HNSCC预防和治疗策略中具有实用性。
This work has demonstrated that a microRNA expression ratio can distinguish between non-diseased tissue and tumor tissue with great accuracy in the context of head and neck squamous cell carcinoma (HNSCC), an important public health concern worldwide. The ratio of miR-221:miR-375 showed high discriminatory potential, with a sensitivity of 92% and specificity of 93% in distinguishing tumor from normal tissue, and suggests that this simple molecular marker may hold significant clinical potential as a diagnostic tool. The involvement of microRNAs (miRNAs) in cancer and their potential as biomarkers of diagnosis and prognosis are becoming increasingly appreciated. We sought to identify miRNAs altered in head and neck squamous cell carcinoma (HNSCC) and to determine whether miRNA expression is predictive of disease. RNA isolated from fresh frozen primary tumors, fresh frozen non-diseased head and neck epithelial tissues, and HNSCC cell lines was profiled for the expression of 662 miRNAs by microarray. The miRNAs that were both differentially expressed on the array and by qRT-PCR were subsequently validated by qRT-PCR using a total of 99 HNSCC samples and 14 normal epithelia. A marked difference in miRNA expression pattern was observed between tumors and cell lines. Eighteen miRNAs were significantly altered in their expression between normal tissues and tumors. Four of these miRNAs were validated in the larger sample series, and each showed significant differential expression (P < 0.0001). Further, an expression ratio of miR-221:miR-375 demonstrated a high sensitivity (0.92) and specificity (0.93) for disease prediction. These data suggest that cultured tumor cell lines are inappropriate for miRNA biomarker identification, and that the pattern of miRNA expression in primary head and neck tissues is reflective of disease status, with certain miRNAs exhibiting strong predictive potential. These results indicate that miR-221 and miR-375 should be evaluated further as diagnostic biomarkers, as they may hold utility in defining broadly responsive prevention and treatment strategies for HNSCC.