A three-gene expression signature associated with positive surgical margins in tongue squamous cell carcinomas: Predicting surgical resectability from tumour biology?. (July 2019)

• Record Type: Journal Article
• Authors: Saidak, Zuzana; Pascual, Caroline; Bouaoud, Jebrane; Galmiche, Louise; Clatot, Florian; Dakpé, Stéphanie; Page, Cyril; Galmiche, Antoine
• Is Part Of: Oral oncology. Volume 94(2019)
• Page Start: 115
• Page End: 120
• Publication Date: 2019-07
• Subjects: Head and neck squamous cell carcinoma -- The Cancer Genome Atlas (TCGA) -- Gene expression -- Surgical margins -- Tongue tumours; ALI angiolymphatic invasion -- AUC Area Under the Curve -- DEG differentially expressed genes -- CNV copy number variations -- ECS extracapsular spread -- FDR false discovery rate -- HNSCC head and neck squamous cell carcinoma -- PNI perineural invasion -- ROC receiver operating characteristic -- SM surgical margins -- TCGA The Cancer Genome Atlas; Mouth -- Cancer -- Periodicals; Mouth -- Tumors -- Periodicals; Mouth Diseases -- Periodicals; Mouth Neoplasms -- Periodicals; Bouche -- Cancer -- Périodiques; Bouche -- Tumeurs -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9943105
• DOI: 10.1016/j.oraloncology.2019.05.020
• Languages: English
• ISSNs: 1368-8375

Abstract

Highlights: Tumour biology was linked with surgical margin (SM) status in HNSCC from TCGA. The genes CCDC66, ZRANB2 and VCPKMT are differentially expressed in tongue tumours with positive SM. The corresponding gene signature identifies tongue tumours with positive SM with high sensitivity and specificity. This signature reflects tumour grade, proliferation levels and stromal content. Abstract: 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.