hsa-mir-210 is a marker of tumor hypoxia and a prognostic factor in head and neck cancer.
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.
Gee
Harriet E
HE
Cancer Research UK Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
Camps
Carme
C
Buffa
Francesca M
FM
Patiar
Shalini
S
Winter
Stuart C
SC
Betts
Guy
G
Homer
Jarrod
J
Corbridge
Rogan
R
Cox
Graham
G
West
Catharine M L
CM
Ragoussis
Jiannis
J
Harris
Adrian L
AL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000032:analysis*; D008875:Middle Aged; D018307:Neoplasms, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D012322:RNA Precursors / Q000032:analysis
D014408:Biomarkers, Tumor; C547183:MIRN10 microRNA, human; C524940:MIRN21 microRNA, human; C543800:MIRN210 microRNA, human; D035683:MicroRNAs; D012322:RNA Precursors