Sushma Pandey1, Tarig A Osman2, Sunita Sharma3, Evan M Vallenari1, Aboulghassem Shahdadfar4, Chin B Pun5, Dej K Gautam6, Lars Uhlin-Hansen7,8, Oddveig Rikardsen9, Anne C Johannessen2,10, Daniela E Costea2,10,11, Dipak Sapkota1. 1. Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway. 2. Department of Clinical Medicine, the Gade Laboratory for Pathology, University of Bergen, Haukeland University Hospital, Bergen, Norway. 3. Department of Clinical Dentistry, Centre for Clinical Dental Research, University of Bergen, Bergen, Norway. 4. Centre for Eye Research, Department of Ophthalmology, Oslo University Hospital, Ullevål, Oslo, Norway. 5. Department of Pathology, B.P. Koirala Memorial Cancer Hospital, Bharatpur, Nepal. 6. Department of Surgical Oncology, B.P. Koirala Memorial Cancer Hospital, Bharatpur, Nepal. 7. Department of Clinical Pathology, University Hospital of North Norway, Tromsø, Norway. 8. Department of Medical Biology-Tumor Biology Research Group, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway. 9. Department of Otorhinolaryngology, University Hospital of North Norway, Tromsø, Norway. 10. Department of Pathology, Haukeland University Hospital, Bergen, Norway. 11. Centre for Cancer Biomarkers (CCBIO), Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
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.
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.