title: Loss of NKX3-1 as a potential marker for an increased risk of occult             lymph node metastasis and poor prognosis in oral squamous cell carcinoma.
abstract: The prognosis of oral squamous cell carcinoma (OSCC) is significantly dependent             on the existence of cervical lymph node metastasis (LNM), with the overall survival             rate being much lower in patients with LNM. Primary causes and molecular mechanisms             of LNM are still largely unclear. We hypothesized that factors related with cancer             progress and/or prognosis in OSCC are revealed by genome-wide investigation of             DNA copy number aberrations (CNAs). In order to find biomarkers for occult LNM             of OSCC, we comprehensively investigated genomic DNAs from 60 OSCC patients using             Affymetrix mapping arrays and statistically analyzed correlations between CNAs             of genes and the presence of occult LNM in the patients. The genome-wide CNA study             indicated significant correlations between the presence of occult LNM and CNAs             of certain genes. Through a literature survey, we narrowed down the candidates             and focused on loss of NKX3-1, which is a homeodomain-containing transcription             factor. NKX3-1 is known as a tumor suppressor gene in prostate cancer but has             never been reported in OSCC. Quantitative RT-PCR and immunohistochemistry (IHC)             analyses also showed significantly lower expression of NKX3-1 in the cases with             occult LNM, which was further validated by IHC analysis in independent cases.             The survival analyses indicated that NKX3-1 loss is a significant risk factor             to decrease the disease-free survival (DFS) and the overall survival (OS) rates.             This is the first time that the significant association of NKX3-1 loss and occult             LNM was indicated in OSCC. The present results suggest that loss of NKX3-1 may             be a potential biomarker for occult LNM of OSCC.
authors.affiliation: Department of Bioinformatics, Graduate School, Tokyo Medical                     and Dental University, Tokyo, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Miyaguchi
authors.forename: Narikazu
authors.initials: N
authors.lastname: Uzawa
authors.forename: Kaoru
authors.initials: K
authors.lastname: Mogushi
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Chieko
authors.initials: C
authors.lastname: Michikawa
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Nakata
authors.forename: Jun
authors.initials: J
authors.lastname: Sumino
authors.forename: Norihiko
authors.initials: N
authors.lastname: Okada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mizushima
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Fukuoka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality / Q000556:secondary*; D016000:Cluster Analysis; D056915:DNA Copy Number Variations; D005260:Female; D055106:Genome-Wide Association Study; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D012307:Risk Factors; D017384:Sequence Deletion; D018709:Statistics, Nonparametric; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; C491178:NKX3-1 protein, human; D014157:Transcription Factors; D042582:Vascular Endothelial Growth Factor C