title: SOX4 expression is closely associated with differentiation and lymph node metastasis in oral squamous cell carcinoma.
abstract: SOX4 is a member of the SOX family of transcription regulators. In recent years, SOX4 was shown to be overexpressed in cancers of various organs and related to epithelial-mesenchymal transition, which is a metastatic factor. This study was the first to investigate correlations between SOX4 expression levels and the clinicopathologic factors of oral squamous cell carcinoma (OSCC). We analyzed SOX4 expression levels in 50 patients with OSCC using immunohistochemistry. All samples expressed the SOX4 protein and elevated SOX4 expression was significantly correlated with gender, T status, and stage levels. The expression level of SOX4 in primary foci of poorly differentiated OSCC was higher than that of well differentiated OSCC, which indicated that SOX4 expression is associated with the differentiation of OSCC. However, regardless of the differentiation level in the primary focus, SOX4 expression levels were found to be very high in the metastatic focus. Furthermore, SOX4 expression in metastatic foci was significantly suppressed by neoadjuvant therapy. These results indicate that undifferentiated OSCC cells expressing SOX4 are more likely to metastasize and neoadjuvant therapy including chemoradiation therapy may have some effect in metastatic prevention.
authors.affiliation: Graduate School of Dentistry, Second Department of Oral and Maxillofacial Surgery, Osaka Dental University, 8-1 Kuzuhahanazono-cho, Hirakata, Osaka, 573-1121, Japan, gamba_0304@yahoo.co.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Watanabe
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ohnishi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Wato
authors.forename: Akio
authors.initials: A
authors.lastname: Tanaka
authors.forename: Kenji
authors.initials: K
authors.lastname: Kakudo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D059186:Chemoradiotherapy, Adjuvant / Q000379:methods; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism*; D020360:Neoadjuvant Therapy / Q000379:methods; D055751:SOXC Transcription Factors / Q000378:metabolism*; D012737:Sex Factors; D018709:Statistics, Nonparametric
chemical_list: C083431:SOX4 protein, human; D055751:SOXC Transcription Factors
references.citation: Am J Pathol. 2010 Dec;177(6):2741-52
references.pmid: 20952589
references.citation: Oncogene. 2010 Feb 25;29(8):1214-26
references.pmid: 19935697
references.citation: Neuro Oncol. 2008 Oct;10(5):648-60
references.pmid: 18577562
references.citation: Oral Oncol. 2010 Jun;46(6):407-10
references.pmid: 20403722
references.citation: Cancer Metastasis Rev. 2007 Dec;26(3-4):645-62
references.pmid: 17768600
references.citation: CA Cancer J Clin. 2010 Sep-Oct;60(5):277-300
references.pmid: 20610543
references.citation: Carcinogenesis. 2010 Jul;31(7):1298-307
references.pmid: 20400479
references.citation: PLoS One. 2012;7(12):e52804
references.pmid: 23285187
references.citation: Nat Cell Biol. 2008 Feb;10(2):202-10
references.pmid: 18193036
references.citation: Nature. 2008 Jan 10;451(7175):147-52
references.pmid: 18185580
references.citation: Cell Stem Cell. 2009 Nov 6;5(5):504-14
references.pmid: 19896441
references.citation: Nature. 2007 Oct 11;449(7163):682-8
references.pmid: 17898713
references.citation: Cancer Res. 2009 Jan 15;69(2):709-17
references.pmid: 19147588
references.citation: Nature. 1990 Jul 19;346(6281):240-4
references.pmid: 1695712
references.citation: Int J Biochem Cell Biol. 2007;39(12):2153-60
references.pmid: 17825600
references.citation: Hum Mol Genet. 2009 Apr 1;18(7):1343-52
references.pmid: 19153074
references.citation: Cancer Res. 2006 Apr 1;66(7):3434-42
references.pmid: 16585165
references.citation: Cancer Res. 2009 Dec 1;69(23):9038-46
references.pmid: 19887623
references.citation: Oncogene. 2006 Sep 14;25(41):5626-39
references.pmid: 16636670
references.citation: EMBO J. 1993 Oct;12(10):3847-54
references.pmid: 8404853
references.citation: Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006 Jul;102(1):67-76
references.pmid: 16831675
references.citation: Mol Cell Biol. 2007 Nov;27(22):7802-15
references.pmid: 17875931
references.citation: Diagn Pathol. 2012 Apr 17;7:41
references.pmid: 22510499
references.citation: Annu Rev Immunol. 2004;22:55-79
references.pmid: 15032574
references.citation: Cancer Res. 2007 Dec 1;67(23):11254-62
references.pmid: 18056451
references.citation: Br J Cancer. 2009 Feb 10;100(3):511-23
references.pmid: 19156145
references.citation: Cancer Cell. 2009 Mar 3;15(3):195-206
references.pmid: 19249678
references.citation: Cancer Res. 2012 Sep 1;72(17):4597-608
references.pmid: 22787120
references.citation: J Mol Endocrinol. 1999 Jun;22(3):295-304
references.pmid: 10343288
references.citation: Cancer Res. 2006 Apr 15;66(8):4011-9
references.pmid: 16618720
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3788-93
references.pmid: 19234109
references.citation: J Neurosci. 2007 May 16;27(20):5495-505
references.pmid: 17507571
references.citation: Mayo Clin Proc. 2007 Jul;82(7):878-87
references.pmid: 17605971
references.citation: Dev Biol. 2000 Nov 15;227(2):239-55
references.pmid: 11071752