Overexpression of TWIST2 correlates with poor prognosis in head and neck squamous cell carcinomas.
Head and neck squamous cell carcinomas (HNSCC) are a heterogeneous group of tumors with variable presentation and clinical behavior. Despite improvements in surgical and radiation therapy techniques, the 5-year survival rate has not improved significantly over the past decades. Thus, there is an urgent need to identify novel markers that may allow for the development of personalized therapeutic approaches. In the present study we evaluated the prognostic role of the expression of genes related to the induction of epithelial mesenchymal transition (EMT). To this aim, a consecutive series of 69 HNSCC were analyzed for the expression of TWIST1, TWIST2, SNAI1, SNAI2, E-Cadherin, N-Cadherin and Vimentin.TWIST1, TWIST2, SNAI1 and SNAI2 were significantly overexpressed in HNSCC, with TWIST2, SNAI1 and SNAI2 being more markedly increased in tumors compared to normal mucosae. The expression of TWIST1 and SNAI2 was associated with upregulation of mesenchymal markers, but failed to correlate with pathological parameters or clinical behaviour. In contrast, we found that upregulation of TWIST2, which was independent of the activation of a mesenchymal differentiation program, correlated with poor differentiation grade (p=0.016) and shorter survival (p=0.025), and identifies a subset of node-positive oral cavity/pharynx cancer patients with very poor prognosis (p less than 0.001). Overall our study suggests that the assessment of TWIST2 expression might help to stratify HNSCC patients for risk of disease progression, pointing to TWIST2 as a potential prognostic marker.
Unit of Experimental Oncology 1, CRO National Cancer Institute, Aviano, Italy.
Daniela
D
Gasparotto
Jerry
J
Polesel
Alessandra
A
Marzotto
Roberta
R
Colladel
Sara
S
Piccinin
Piergiorgio
P
Modena
Alessandra
A
Grizzo
Sandro
S
Sulfaro
Diego
D
Serraino
Luigi
L
Barzan
Claudio
C
Doglioni
Roberta
R
Maestro
D014408:Biomarkers, Tumor; D015820:Cadherins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism; D011379:Prognosis; D012097:Repressor Proteins / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D000077195:Squamous Cell Carcinoma of Head and Neck; D014157:Transcription Factors / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism
D014408:Biomarkers, Tumor; D015820:Cadherins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C000604407:SNAI1 protein, human; C000604408:SNAI2 protein, human; D000071250:Snail Family Transcription Factors; C103173:TWIST1 protein, human; C486274:TWIST2 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1; D014746:Vimentin