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

Miyaguchi,Ken; Uzawa,Narikazu; Mogushi,Kaoru; Takahashi,Ken-Ichiro; Michikawa,Chieko; Nakata,Yoshimi; Sumino,Jun; Okada,Norihiko; Mizushima,Hiroshi; Fukuoka,Yutaka; Tanaka,Hiroshi

doi:10.3892/ijo.2012.1373

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

Authors:
- Ken Miyaguchi
- Narikazu Uzawa
- Kaoru Mogushi
- Ken-Ichiro Takahashi
- Chieko Michikawa
- Yoshimi Nakata
- Jun Sumino
- Norihiko Okada
- Hiroshi Mizushima
- Yutaka Fukuoka
- Hiroshi Tanaka
View Affiliations

Affiliations: Department of Bioinformatics, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan, Department of Maxillofacial Surgery, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan, Department of Computational Biology, Graduate School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan, Department of Diagnostic Oral Pathology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan, Center for Public Health Informatics, National Institute of Public Health, Tokyo, Japan, Department of Biosystem Modeling, Graduate School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan
Published online on: February 14, 2012 https://doi.org/10.3892/ijo.2012.1373
Pages: 1907-1914

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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.