Gene expression profiling of perineural invasion in head and neck cutaneous squamous cell carcinoma

Jonathan R. Clark,Nicholas West,Timothy J. Eviston,Navid Ahmadi,Ruta Gupta,Bruce Ashford,Simon A. Mueller,Elahe Minaei,Marie Ranson,Ping Zhang

doi:10.1038/s41598-021-92335-4

Abstract

Perineural invasion (PNI) is frequently associated with aggressive clinical behaviour in head and neck cutaneous squamous cell carcinoma (HNcSCC) leading to local recurrence and treatment failure. This study evaluates the gene expression profiles of HNcSCC with PNI using a differential expression analysis approach and constructs a tailored gene panel for sensitivity and specificity analysis. 45 cases of HNcSCC were stratified into three groups (Extensive, Focal and Non PNI) based on predefined clinicopathological criteria. Here we show HNcSCC with extensive PNI demonstrates significant up- and down-regulation of 144 genes associated with extracellular matrix interactions, epithelial to mesenchymal transition, cell adhesion, cellular motility, angiogenesis, and cellular differentiation. Gene expression of focal and non PNI cohorts were indistinguishable and were combined for further analyses. There is clinicopathological correlation between gene expression analysis findings and disease behaviour and a tailored panel of 10 genes was able to identify extensive PNI with 96% sensitivity and 95% specificity.

Highlights

Perineural invasion (PNI) is frequently associated with aggressive clinical behaviour in head and neck cutaneous squamous cell carcinoma (HNcSCC) leading to local recurrence and treatment failure
The final cohort of 45 patients (6 females and 39 males) were classified into three groups based on pathological criteria (Non-PNI, Focal-PNI, EXT-PNI)
Consistent with the gene expression profiling, the Non-PNI and Focal-PNI groups were combined for analysis

Summary

Introduction

Perineural invasion (PNI) is frequently associated with aggressive clinical behaviour in head and neck cutaneous squamous cell carcinoma (HNcSCC) leading to local recurrence and treatment failure. There is clinicopathological correlation between gene expression analysis findings and disease behaviour and a tailored panel of 10 genes was able to identify extensive PNI with 96%. Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy and frequently occurs in the head and neck[1]. This cancer is treated by a diverse range of clinicians including surgeons, primary care physicians and dermatologists. Perineural invasion (PNI) is an established adverse prognostic factor in multiple malignancies including head and neck cutaneous squamous cell carcinoma (HNcSCC)[2,3,4].

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