Low-level expression of microRNAs let-7d and miR-205 are prognostic markers of head and neck squamous cell carcinoma

Geoffrey Childs, Melissa Fazzari, Gloria Kung, Nicole Kawachi, Margaret Brandwein-Gensler, Michael McLemore, Quan Chen, Robert D. Burk, Richard V. Smith, Michael B. Prystowsky, Thomas J. Belbin, Nicolas F. Schlecht

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)736-745
Number of pages10
JournalAmerican Journal of Pathology
Volume174
Issue number3
DOIs
StatePublished - Mar 2009

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MicroRNAs
Neoplasms
Head and Neck Neoplasms
Real-Time Polymerase Chain Reaction
Survival
Carcinoma, squamous cell of head and neck
Statistical Models
Microarray Analysis
Cell Differentiation
Cell Proliferation
Apoptosis
Recurrence
Therapeutics

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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Low-level expression of microRNAs let-7d and miR-205 are prognostic markers of head and neck squamous cell carcinoma. / 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.

In: American Journal of Pathology, Vol. 174, No. 3, 03.2009, p. 736-745.

Research output: Contribution to journalArticle

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. / Low-level expression of microRNAs let-7d and miR-205 are prognostic markers of head and neck squamous cell carcinoma. In: American Journal of Pathology. 2009 ; Vol. 174, No. 3. pp. 736-745.
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