hsa‐miR‐210 is a marker of tumor hypoxia and a prognostic factor in head and neck cancer

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 ¼ 0.67, P < .001). We found no association between hsa-miR-210, hsamiR-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 ¼ .001) and short overall survival (P ¼ .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.

MicroRNA-210 Regulates Cancer Cell Proliferation through Targeting Fibroblast Growth Factor Receptor-like 1 (FGFRL1)

“…In contrast to our study, miR-210 was reported to be upregulated in breast cancer, pancreatic tumors, and head and neck cancer and to be correlated with their poor outcome (21)(22)(23)(24). Moreover, previous studies have shown that miR-210 inhibits apoptosis and bypasses cell cycle arrest in cancer cell lines such as MCF-7 and HCT116 Dicer ex5 cells (25,26).…”

MicroRNA expression patterns in adrenocortical carcinoma variants and clinical pathologic correlations

“…Concerning the importance of histological variant in ACC clinical outcome, we have confirmed the results of a retrospective survival analysis provided by Wong et al [26], in which was shown a better prognosis for malignant adrenocortical neoplasm showing predominant oncocytic features in comparison with those of classical type. The prognostic value of miR-210 has already been demonstrated in breast [33], pancreatic [34], head and neck carcinomas [35], pediatric osteosarcoma [36], and glioblastoma [37].…”

MicroRNA: Potential Targets for the Development of Novel Drugs?

“…miRNA appears to be a reliable biomarker for diagnosis, prognosis, and treatment evaluation in different types of cancers. [40][41][42] miRNA expression profiles could be used to define the cell types, [2,3] thereby allowing detection of the miRNA biomarker or expression signatures from patients in order to develop individualized therapeutic plans, possibly even targeting specific miRNAs for a given patient. Furthermore, the understanding of how an individual's genetic inheritance of miRNA polymorphisms affects the body's response to certain drugs will be key to creating drugs with greater efficacy and safety.…”