Low-Level Expression of MicroRNAs let-7d and miR-205 Are Prognostic Markers of Head and Neck Squamous Cell Carcinoma
Low-Level Expression of MicroRNAs let-7d and miR-205 Are Prognostic Markers of Head and Neck Squamous Cell Carcinoma
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DOI：
10.2353/ajpath.2009.080731
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发表时间：
2009-03-01
影响因子：
6
通讯作者：
Schlecht, Nicolas F.
中科院分区：
文献类型：
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作者：
Childs, Geoffrey;Fazzari, Melissa;Schlecht, Nicolas F.
小的非编码microRNAs(MiRNAs)已被证明在所研究的每一种肿瘤类型中都异常表达。MiRNAs作为潜在的癌症预后指标的重要性被强调，因为它们参与了基本的细胞过程的调节，如细胞的增殖、分化和凋亡。本研究采用基因芯片技术检测了头颈部鳞状细胞癌(HNSCC)肿瘤及癌旁正常组织中miRNA的表达谱，并用TaqMan实时定量聚合酶链式反应对其进行了验证。使用TaqMan实时聚合酶链式反应，我们在104名接受治疗的HNSCC患者队列中，测量了诊断时在原发灶中微阵列上鉴定的miRNAs子集与癌症存活率之间的定量关联。在原发HNSCC肿瘤(包括miR-1、miR-133a、miR-205和let-7d)中，大多数miRNAs的表达水平低于正常癌旁组织。相反，BSA-miR-21在人类HNSCC肿瘤中经常过表达。使用单变量和多变量统计模型，我们表明低水平的hsa-miR205与局部复发显着相关，与诊断和治疗时的疾病严重程度无关。此外，hsa-miR-205和hsa-let-7d在HNSCC肿瘤中的低表达与头颈部肿瘤的预后显著相关。我们的研究结果表明，miRNA的表达水平可以作为头颈癌的预后指标。(Am J Pathol 2009174：736-745；DOI：10.2353/ajpath.2009.080731)
Small noncoding microRNAs (miRNAs) have been shown to be abnormally expressed in every tumor type examined. The importance of miRNAs as potential cancer prognostic indicators is underscored by their involvement in the regulation of basic cellular processes such as cell proliferation, differentiation, and apoptosis. in this study, miRNA expression profiles of head and neck squamous cell carcinoma (HNSCC) tumor and adjacent normal tissue were examined by microarray analysis and validated by quantitative TaqMan real-time polymerase chain reaction. Using TaqMan real-time polymerase chain reaction we measured the quantitative associations between a subset of miRNAs identified on microarrays in primary tumors at diagnosis and cancer survival in a cohort of 104 HNSCC patients undergoing treatment with curative intent. The majority of miRNAs exhibiting altered expression in primary human HNSCC tumors (including miR-1, miR-133a, miR-205, and let-7d) show lower expression levels relative to normal adjacent tissue. in contrast, bsa-miR-21 is frequently overexpressed in human HNSCC tumors. Using univariate and multivariable statistical models we show that low levels of hsa-miR205 are significantly associated with loco-regional recurrence independent of disease severity at diagnosis and treatment. In addition, combined low levels of hsa-miR-205 and hsa-let-7d expression in HNSCC tumors are significantly associated with poor head and neck cancer survival Our results show that miRNA expression levels can be used as prognostic markers of head and neck cancer. (Am J Pathol 2009, 174:736-745; DOI: 10.2353/ajpath.2009.080731)