Low-Level Expression of MicroRNAs let-7d and miR-205 Are Prognostic Markers of Head and Neck Squamous Cell Carcinoma

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...

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Veröffentlicht in:The American journal of pathology 2009-03, Vol.174 (3), p.736-745
Hauptverfasser: Childs, Geoffrey, Fazzari, Melissa, Kung, Gloria, Kawachi, Nicole, Brandwein-Gensler, Margaret, McLemore, Michael, Chen, Quan, Burk, Robert D, Smith, Richard V, Prystowsky, Michael B, Belbin, Thomas J, Schlecht, Nicolas F
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container_title The American journal of pathology
container_volume 174
creator Childs, Geoffrey
Fazzari, Melissa
Kung, Gloria
Kawachi, Nicole
Brandwein-Gensler, Margaret
McLemore, Michael
Chen, Quan
Burk, Robert D
Smith, Richard V
Prystowsky, Michael B
Belbin, Thomas J
Schlecht, Nicolas F
description 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, hsa-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.
doi_str_mv 10.2353/ajpath.2009.080731
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subjects Biological and medical sciences
Carcinoma, Squamous Cell - genetics
Carcinoma, Squamous Cell - mortality
Carcinoma, Squamous Cell - pathology
Female
Gene Expression Regulation, Neoplastic
Head and Neck Neoplasms - genetics
Head and Neck Neoplasms - mortality
Head and Neck Neoplasms - pathology
Humans
Investigative techniques, diagnostic techniques (general aspects)
Male
Medical sciences
MicroRNAs - genetics
MicroRNAs - isolation & purification
Middle Aged
Neoplasm Staging
Otorhinolaryngology (head neck, general aspects and miscellaneous)
Otorhinolaryngology. Stomatology
Pathology
Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques
Polymerase Chain Reaction
Prognosis
Reference Values
Regular
RNA, Neoplasm - genetics
RNA, Neoplasm - isolation & purification
Survival Analysis
Survivors
Tumors
title Low-Level Expression of MicroRNAs let-7d and miR-205 Are Prognostic Markers of Head and Neck Squamous Cell Carcinoma
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