Loss of S100A14 expression at the tumor-invading front correlates with poor differentiation and worse prognosis in oral squamous cell carcinoma

Head Neck. 2020 Aug;42(8):2088-2098. doi: 10.1002/hed.26140. Epub 2020 Mar 23.

Abstract

Background: We previously showed a tumor-suppressive function of S100A14 in oral squamous cell carcinoma (OSCC). This study aimed to examine the prognostic significance and differentiation-related function of S100A14 in OSCC.

Methods: S100A14 expression was examined in 170 OSCCs from Norwegian and Nepalese populations using immunohistochemistry. Pro-differentiation function was investigated by overexpressing and silencing S100A14 expression in OSCC-derived cells. External transcriptomic datasets were used to validate association between S100A14 and differentiation markers in OSCC.

Result: Loss of S100A14 expression at the invading tumor fronts significantly correlated with poor differentiation and reduced 10-years survival of OSCC-patients. Multivariate Cox analysis identified S100A14 to be an independent prognostic factor. Modulation of S100A14 expression in OSCC-derived cells positively correlated with the expression of differentiation markers. Analysis of external datasets supported the pro-differentiation function of S100A14.

Conclusion: These results indicate that S100A14 is a pro-differentiation protein and its expression might be useful as a prognostic marker in OSCC.

Keywords: Nepal; Norway; S100; oral cancer; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Calcium-Binding Proteins / genetics*
  • Carcinoma, Squamous Cell* / genetics
  • Cell Differentiation
  • Cell Line, Tumor
  • Head and Neck Neoplasms*
  • Humans
  • Mouth Neoplasms* / genetics
  • Prognosis
  • Squamous Cell Carcinoma of Head and Neck

Substances

  • Biomarkers, Tumor
  • Calcium-Binding Proteins
  • S100A14 protein, human