Low-Level Expression of miR-375 Correlates with Poor Outcome and Metastasis While Altering the Invasive Properties of Head and Neck Squamous Cell Carcinomas
Low-Level Expression of miR-375 Correlates with Poor Outcome and Metastasis While Altering the Invasive Properties of Head and Neck Squamous Cell Carcinomas
复制标题
DOI：
10.1016/j.ajpath.2011.12.004
复制
发表时间：
2012-03-01
影响因子：
6
通讯作者：
Childs, Geoffrey
中科院分区：
文献类型：
--
作者：
Harris, Thomas;Jimenez, Lizandra;Childs, Geoffrey
小的非编码 microRNA (miRNA) 已被证明在所检查的每种肿瘤类型中都异常表达。我们通过比较头颈鳞状细胞癌 (HNSCC) 样本和邻近正常组织的整体 miRNA 表达谱，对我们的患者群体中变化最显着的 miRNA 进行排序。排名一致性评分分析显示，在评估的 736 个 miRNA 中，相对于来自同一患者的匹配的邻近非恶性组织，miR-375 在肿瘤中的 miRNA 水平降低最显着。这一结果之前已被其他研究组观察到；然而，我们通过独特的观察扩展了这一发现，即低 miR-375 表达水平与癌症存活和远处转移显着相关。在一项使用多变量 Cox 比例风险比 (HR) 和 95% 置信区间 (CI) 对 123 名原发性 HNSCC 患者进行的研究中，疾病死亡（HR：12.8，95% CI：3 至 49）和远处转移发生率（HR：8.7，95% CI：2 至 31）与 miR-375 的较低表达水平相关，无论肿瘤的部位或阶段如何。此外，我们发现过表达 miR-375 的口腔肿瘤细胞系（例如 UMSCC1 和 UMSCC47）在体外的侵袭性明显低于其匹配的空载体对照。我们得出的结论是，miR-375 代表了 HNSCC 预后不良和转移的潜在预后标志物，并且它可能通过抑制肿瘤的侵袭特性来发挥作用。 （Ant J Pathol 2012，180：917-928。DOI：10.1016/j.ajpath.2011.12.004）
Small, noncoding microRNAs (miRNAs) have been shown to be abnormally expressed in every tumor type examined. We used comparisons of global miRNA expression profiles of head and neck squamous cell carcinoma (HNSCC) samples and adjacent normal tissue to rank those miRNAs that were most significantly altered in our patient population. Rank Consistency Score analysis revealed miR-375 to have the most significantly lowered miRNA levels in tumors relative to matched adjacent nonmalignant tissue from the same patient among 736 miRNAs that were evaluated. This result has been previously observed by other groups; however, we extend this finding with the unique observation that low miR-375 expression levels correlate significantly with cancer survival and distant metastasis. In a study of 123 primary HNSCC patients using multivariable Cox proportional hazard ratios (HR) and 95% confidence intervals (CI), both death from disease (HR: 12.8, 95% Cl: 3 to 49) and incidence of distant metastasis (HR: 8.7, 95% CI: 2 to 31) correlated with lower expression levels of miR-375 regardless of the site or stage of the tumor. In addition, we found that oral cavity tumor cell lines (eg, UMSCC1 and UMSCC47) overexpressing miR-375 were significantly less invasive in vitro than their matched empty vector controls. We conclude that miR-375 represents a potential prognostic marker of poor outcome and metastasis in HNSCC and that it may function by suppressing the tumor's invasive properties. (Ant J Pathol 2012, 180:917-928. DOI: 10.1016/j.ajpath.2011.12.004)