A gene expression profile associated with perineural invasion identifies a subset of HNSCC at risk of post-surgical recurrence. (November 2018)

• Record Type: Journal Article
• Authors: Saidak, Zuzana; Clatot, Florian; Chatelain, Denis; Galmiche, Antoine
• Is Part Of: Oral oncology. Volume 86(2018)
• Page Start: 53
• Page End: 60
• Publication Date: 2018-11
• Subjects: Head and neck squamous cell carcinoma -- Perineural invasion -- The Cancer Genome Atlas (TCGA) -- Gene expression; ALI angiolymphatic invasion -- CPE consensus purity estimation score -- DFS disease free survival -- ECS extracapsular spread -- FDR false discovery rate -- GO gene ontology -- HNSCC head and neck squamous cell carcinoma -- mTOR mammalian Target Of Rapamycin -- OS overall survival -- PNI perineural invasion -- RPPA Reverse Phase Protein Array -- SM positive surgical margin -- 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.2018.09.005
• Languages: English
• ISSNs: 1368-8375

Abstract

Highlights: Perineural invasion (PNI) is explored at the system biology level in HNSCC tumours from TCGA. PNI is associated with a gene expression profile enriched in muscle genes. This gene expression profile identifies a subset of HNSCC at risk of post-surgical recurrence. HNSCC tumours with PNI have increased activation levels of the Akt/PKB and mTOR kinases. Abstract: Objectives: Perineural invasion (PNI) is a common histopathological finding in head and neck squamous cell carcinoma (HNSCC). We aimed to explore the molecular mechanisms involved in PNI and the role of PNI as an aggressive pathological feature. Materials and methods: We used data from The Cancer Genome Atlas (TCGA) to relate the histological presentation of 528 HNSCC tumours to clinical, whole genome expression and proteomic data. Results: We identified a specific gene expression profile highly enriched in genes related to muscle differentiation/function and associated with PNI in HNSCC. We explored the clinical significance of this profile in three groups of HNSCC tumours stratified according to their low, intermediate or high risk of post-surgical recurrence. In the "low-risk" group, defined as tumours indicated for surgery without adjuvant radiotherapy (n = 51), the PNI gene expression profile identified a subset of HNSCC with a higher rate of tumour recurrence, decreased Disease Free Survival (DFS) and Overall Survival (OS) (p < 0.0001 and p = 0.0064, respectively). Comparable results were observed in "intermediate risk" tumours (n = 112), but not in "high risk" tumours (n = 147), whose prognosis was driven by the presence of lymph node extracapsular spread. Finally, we found that tumours with histological PNI had increased activation levels of the Akt/PKB and mTOR (mammalian Target Of Rapamycin) kinases. Conclusion: PNI is characterised by a specific gene expression profile and distinct biological characteristics. Analysing the PNI gene expression profile holds potential for therapeutic stratification of HNSCC and identification of a subset of tumours with a higher risk of recurrence.