A three-gene expression signature associated with positive surgical margins in tongue squamous cell carcinomas: Predicting surgical resectability from tumour biology?

Zuzana Saidak (1) , Caroline Pascual (1) , Jebrane Bouaoud (2, 3) , Louise Galmiche (4) , Florian Clatot (5, 6) , Stéphanie Dakpé (1) , Cyril Page (7) , Antoine Galmiche (1, 7)

1 CHIMERE - CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516
2 CMF et Stomatologie - Chirurgie maxillofaciale et Stomatologie [CHU Amiens]
3 CHU Pitié-Salpêtrière [AP-HP]
4 Service de pathologie [CHU Necker]
5 GPMCND - Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques
6 CLCC Henri Becquerel - Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen
7 CHU Amiens-Picardie

Objectives: Achieving complete tumour resection is one of the main goals of surgery for head and neck squamous cell carcinoma (HNSCC) tumours. Whether biological characteristics of tumours contribute to the surgical resectability and the presence of positive surgical margins (SM) after resection of HNSCC is unclear. We aimed to address this issue. Materials and methods: We used data from The Cancer Genome Atlas (TCGA) to relate the SM status of 356 HNSCC tumours covering five major primary locations (tongue, larynx, tonsils, floor of mouth and buccal mucosa) with data from multiple omics approaches (transcriptomic, genomic and proteomic analyses). Results: We identified three differentially expressed genes whose expression was significantly associated with the presence of positive SM in tongue tumours (n = 144). The three genes (CCDC66, ZRANB2 and VCPKMT) displayed significantly higher mRNA levels in tongue tumours with positive SM compared to tumours with negative SM. The corresponding gene expression signature identified tongue tumours with a positive SM with high sensitivity and specificity (85% and 76%, respectively, Area Under the Curve (AUC) = 0.84). Tongue tumours with this signature were characterised by a high grade, elevated proliferation levels and a tumour stroma with fewer fibroblasts and endothelial cells. Conclusion: Positive SM were found to be strikingly associated with tumour biology in tongue tumours. These findings offer interesting perspectives for biomarker identification and precision surgery in these tumours.

Mots clés: Gene expression; Head and neck squamous cell carcinoma; Surgical margins; The Cancer Genome Atlas (TCGA); Tongue tumours.

Domaines: Cancer

Zuzana Saidak, Caroline Pascual, Jebrane Bouaoud, Louise Galmiche, Florian Clatot, et al.. A three-gene expression signature associated with positive surgical margins in tongue squamous cell carcinomas: Predicting surgical resectability from tumour biology?. Oral Oncology, 2019, 94, pp.115-120. ⟨10.1016/j.oraloncology.2019.05.020⟩. ⟨hal-02352881⟩