hsa-mir-210 Is a Marker of Tumor Hypoxia and a Prognostic Factor in Head and Neck Cancer
hsa-mir-210 Is a Marker of Tumor Hypoxia and a Prognostic Factor in Head and Neck Cancer
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DOI：
10.1002/cncr.25009
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发表时间：
2010-05-01
期刊：
影响因子：
6.2
通讯作者：
Harris, Adrian L.
中科院分区：
文献类型：
--
作者：
Gee, Harriet E.;Camps, Carme;Harris, Adrian L.
背景：缺氧是头颈部鳞状细胞癌耐药的重要机制。microRNA是调节多种mRNA的短的非编码RNA，并且在癌症中经常失调。作者研究了3种microRNA的作用，包括缺氧诱导的hsa-miR-210，作为缺氧或预后的潜在标志物。方法：在46例HNSCC患者的样本中检测3种缺氧相关microRNA hsa-miR-210、hsa-miR-21和hsa-miR-10 b。表达水平与临床病理变量和其他缺氧标志物相关：已发表的99个基因缺氧元基因，个别缺氧相关基因，如TWIST 1，缺氧诱导因子1及其靶基因碳酸酐酶9的免疫组化表达。然后，我们进行了生存分析，以研究这些microRNA的预后意义。研究结果：只有hsa-miR-210的水平与其他缺氧标志物显著相关，包括99基因缺氧多基因（rho = 0.67，P < .001）。我们发现hsa-miR-210、hsa-miR-21或hsa-miR-10 b与临床病理变量（如肿瘤大小、分化和分期）之间无相关性。然而，高水平的hsa-miR-210与局部疾病复发（P = 0.001）和总生存期短（P = 0.008）相关。hsa-miR-21和hsa-miR-10 b与预后无显著性差异。结论：hsa-miR-210在头颈癌中的表达与其他评估缺氧的方法相关，并与预后相关。这保证了进一步的研究，作为涉及缺氧调节治疗的患者的分类标志。Cancer 2010;116：2148-58. (C)2010美国癌症协会
BACKGROUND: Hypoxia is an important mechanism of treatment resistance in head and neck squamous cell carcinoma (HNSCC). MicroRNAs are short noncoding RNAs that regulate multiple mRNAs and are frequently dysregulated in cancer. The authors have investigated the role of 3 microRNAs, including the hypoxia-induced hsa-miR-210, as potential markers of hypoxia or prognosis. METHODS: Three hypoxia-related microRNAs, hsa-miR-210, hsa-miR-21, and hsa-miR-10b, were measured in 46 samples from patients with HNSCC. Expression levels were correlated with clinicopathological variables and other markers of hypoxia: a published 99-gene hypoxia metagene, individual hypoxia-related genes such as TWIST1, and immunohistochemical expression of hypoxia-inducible factor 1 and its target gene carbonic anhydrase 9. We then performed survival analyses to investigate the prognostic significance of these microRNAs. RESULTS: Only the level of hsa-miR-210 was significantly correlated with other markers of hypoxia, including the 99-gene hypoxia metagene (rho = 0.67, P < .001). We found no association between hsa-miR-210, hsa-miR-21, or hsa-miR-10b and clinicopathological variables such as tumor size, differentiation, and stage. However, high levels of hsa-miR-210 were associated with locoregional disease recurrence (P = .001) and short overall survival (P = .008). hsa-miR-21 and hsa-miR-10b had no prognostic significance. CONCLUSIONS: Expression of hsa-miR-210 in head and neck cancer correlates with other approaches for assessing hypoxia and is associated with prognosis. This warrants further study as a classification marker of patients for therapies involving modulation of hypoxia. Cancer 2010;116:2148-58. (C) 2010 American Cancer Society.