Association of OCT4, SOX2, and NANOG expression with oral squamous cell carcinoma progression

J Oral Pathol Med. 2016 Feb;45(2):89-95. doi: 10.1111/jop.12335. Epub 2015 Jul 25.

Abstract

Background: OCT4, SOX2, and NANOG are major transcription factors related to stem cell self-renewal and differentiation. The aim of this study was to examine the association of OCT4, SOX2, and NANOG expression levels with the development and prognosis of patients with oral squamous cell carcinoma (OSCC).

Materials and methods: Expression levels of OCT4, SOX2, and NANOG were evaluated by immunohistochemistry with tissue microarray slides of 436 OSCC, 362 corresponding tumor-adjacent normal (CTAN) tissues, and 71 normal uvula epithelium tissues. The clinicopathologic and follow-up data of the OSCC patients were recorded.

Results: OCT4 expression was significantly higher in normal and CTAN tissues than in tumor tissue (both P < 0.001). SOX2 expression in CTAN tissue was significantly higher than that in normal (P = 0.021) and tumor tissues (P < 0.001). However, NANOG expression was significantly higher in CTAN (P = 0.014) and tumor tissues (P = 0.009) than in normal tissue. Higher OCT4 and SOX2 expressions were associated with earlier AJCC stage (P = 0.002 and P < 0.001), small tumor size (P = 0.017 and P = 0.001), and the absence of lymph node metastasis (P = 0.015 and P = 0.025). Higher levels of SOX2 expression were associated with better disease-specific survival (P = 0.002) even after adjustment for clinicopathologic factors.

Discussion: OCT4 and SOX2 are biomarkers of tumorigenesis and early stage OSCC. SOX2 is an independent prognostic factor for OSCC.

Keywords: NANOG; OCT4; SOX2; oral cancer; squamous cell carcinoma.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor* / biosynthesis
  • Biomarkers, Tumor* / genetics
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Disease Progression*
  • Female
  • Humans
  • Lymphatic Metastasis / pathology
  • Male
  • Middle Aged
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / pathology
  • Nanog Homeobox Protein / biosynthesis*
  • Nanog Homeobox Protein / genetics
  • Nanog Homeobox Protein / metabolism
  • Neoplastic Stem Cells / pathology
  • Octamer Transcription Factor-3 / biosynthesis*
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism
  • Prognosis
  • SOXB1 Transcription Factors / biosynthesis*
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism
  • Transcription Factors / metabolism
  • Young Adult

Substances

  • Biomarkers, Tumor
  • NANOG protein, human
  • Nanog Homeobox Protein
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • Transcription Factors