hsa-mir-210 是肿瘤乏氧的标志物和头颈部癌症的预后因素。

hsa-mir-210 is a marker of tumor hypoxia and a prognostic factor in head and neck cancer.

机构信息

Cancer Research UK Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.

出版信息

Cancer. 2010 May 1;116(9):2148-58. doi: 10.1002/cncr.25009.

DOI:10.1002/cncr.25009

PMID:20187102

Abstract

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.

摘要

背景

缺氧是头颈部鳞状细胞癌（HNSCC）治疗耐药的重要机制。miRNAs 是短的非编码 RNA，可调节多个 mRNA，并且在癌症中经常失调。作者研究了 3 种 microRNAs（包括缺氧诱导的 hsa-miR-210）作为潜在的缺氧或预后标志物的作用。

方法

在 46 例 HNSCC 患者的样本中测量了 3 种与缺氧相关的 microRNAs（hsa-miR-210、hsa-miR-21 和 hsa-miR-10b）。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 基因缺氧荟萃基因、TWIST1 等个别缺氧相关基因以及缺氧诱导因子 1 及其靶基因碳酸酐酶 9 的免疫组织化学表达。然后，我们进行了生存分析，以研究这些 microRNAs 的预后意义。

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 基因缺氧荟萃基因（rho = 0.67，P <.001）。我们没有发现 hsa-miR-210、hsa-miR-21 或 hsa-miR-10b 与肿瘤大小、分化和分期等临床病理变量之间的关联。然而，高水平的 hsa-miR-210 与局部区域疾病复发（P =.001）和总生存时间短（P =.008）相关。hsa-miR-21 和 hsa-miR-10b 没有预后意义。