Low-level expression of miR-375 correlates with poor outcome and metastasis while altering the invasive properties of head and neck squamous cell carcinomas

Thomas M. Harris, Lizandra Jimenez, Nicole Kawachi, Jian Bing Fan, Jing Chen, Tom Belbin, Andrew Ramnauth, Olivier Loudig, Christian E. Keller, Richard V. Smith, Michael B. Prystowsky, Nicolas F. Schlecht, Jeffrey E. Segall, Geoffrey J. Childs

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Abstract

Small, noncoding microRNAs (miRNAs) have been shown to be abnormally expressed in every tumor type examined. We used comparisons of global miRNA expression profiles of head and neck squamous cell carcinoma (HNSCC) samples and adjacent normal tissue to rank those miRNAs that were most significantly altered in our patient population. Rank Consistency Score analysis revealed miR-375 to have the most significantly lowered miRNA levels in tumors relative to matched adjacent nonmalignant tissue from the same patient among 736 miRNAs that were evaluated. This result has been previously observed by other groups; however, we extend this finding with the unique observation that low miR-375 expression levels correlate significantly with cancer survival and distant metastasis. In a study of 123 primary HNSCC patients using multivariable Cox proportional hazard ratios (HR) and 95% confidence intervals (CI), both death from disease (HR: 12.8, 95% CI: 3 to 49) and incidence of distant metastasis (HR: 8.7, 95% CI: 2 to 31) correlated with lower expression levels of miR-375 regardless of the site or stage of the tumor. In addition, we found that oral cavity tumor cell lines (eg, UMSCC1 and UMSCC47) overexpressing miR-375 were significantly less invasive in vitro than their matched empty vector controls. We conclude that miR-375 represents a potential prognostic marker of poor outcome and metastasis in HNSCC and that it may function by suppressing the tumor's invasive properties.

Original languageEnglish (US)
Pages (from-to)917-928
Number of pages12
JournalAmerican Journal of Pathology
Volume180
Issue number3
DOIs
StatePublished - Mar 2012

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MicroRNAs
Neoplasm Metastasis
Confidence Intervals
Neoplasms
Tumor Cell Line
Mouth
Carcinoma, squamous cell of head and neck
Survival
Incidence
Population

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Low-level expression of miR-375 correlates with poor outcome and metastasis while altering the invasive properties of head and neck squamous cell carcinomas. / Harris, Thomas M.; Jimenez, Lizandra; Kawachi, Nicole; Fan, Jian Bing; Chen, Jing; Belbin, Tom; Ramnauth, Andrew; Loudig, Olivier; Keller, Christian E.; Smith, Richard V.; Prystowsky, Michael B.; Schlecht, Nicolas F.; Segall, Jeffrey E.; Childs, Geoffrey J.

In: American Journal of Pathology, Vol. 180, No. 3, 03.2012, p. 917-928.

Research output: Contribution to journalArticle

Harris, Thomas M. ; Jimenez, Lizandra ; Kawachi, Nicole ; Fan, Jian Bing ; Chen, Jing ; Belbin, Tom ; Ramnauth, Andrew ; Loudig, Olivier ; Keller, Christian E. ; Smith, Richard V. ; Prystowsky, Michael B. ; Schlecht, Nicolas F. ; Segall, Jeffrey E. ; Childs, Geoffrey J. / Low-level expression of miR-375 correlates with poor outcome and metastasis while altering the invasive properties of head and neck squamous cell carcinomas. In: American Journal of Pathology. 2012 ; Vol. 180, No. 3. pp. 917-928.
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AU - Chen, Jing

AU - Belbin, Tom

AU - Ramnauth, Andrew

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