title: Low-level expression of miR-375 correlates with poor outcome and metastasis while altering the invasive properties of head and neck squamous cell carcinomas.
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.
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Thomas
authors.initials: T
authors.lastname: Harris
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Lizandra
authors.initials: L
authors.lastname: Jimenez
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Nicole
authors.initials: N
authors.lastname: Kawachi
authors.affiliation: Illumina Inc., San Diego, California.
authors.forename: Jian-Bing
authors.initials: JB
authors.lastname: Fan
authors.affiliation: Illumina Inc., San Diego, California.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Tom
authors.initials: T
authors.lastname: Belbin
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Andrew
authors.initials: A
authors.lastname: Ramnauth
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Olivier
authors.initials: O
authors.lastname: Loudig
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Christian E
authors.initials: CE
authors.lastname: Keller
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Montefiore Medical Center, Bronx, New York.
authors.forename: Richard
authors.initials: R
authors.lastname: Smith
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Prystowsky
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Nicolas F
authors.initials: NF
authors.lastname: Schlecht
authors.affiliation: Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Segall
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, New York. Electronic address: geoffrey.childs@einstein.yu.edu.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Childs
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality*; D045744:Cell Line, Tumor; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000401:mortality*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D011446:Prospective Studies; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: C540933:MIRN375 microRNA, human; D035683:MicroRNAs; D004815:Epidermal Growth Factor