High expression of myoferlin is associated with poor outcome in oropharyngeal squamous cell carcinoma patients and is inversely associated with HPV-status.

Bhavna Kumar,Theodoros N Teknos,Benjamin J Swanson,David E Schuller,Pawan Kumar,Amit Agrawal,Nicole V Brown,Alessandra C Schmitt,Matthew Old,Enver Ozer

doi:10.18632/oncotarget.7625

Bhavna Kumar, Theodoros N Teknos + Show 8 more

Open Access

https://doi.org/10.18632/oncotarget.7625

Copy DOI

Journal: Oncotarget	Publication Date: Feb 23, 2016
Citations: 28	License type: cc-by

Affiliation: The Ohio State University, Emory University

Abstract

Myoferlin (MYOF) is a member of ferlin family of membrane proteins that was originally discovered as a muscle specific protein. Recent studies have shown that myoferlin is also expressed in other cell types including endothelial cells and cancer cells. However, very little is known about the expression and biological role of myoferlin in head and neck cancer. In this study, we examined expression profile of myoferlin in oropharyngeal squamous cell carcinoma (OPSCC) and assessed its correlation with disease progression and patient outcome. In univariate analyses, nuclear MYOF was associated with poor overall survival (p<0.001) and these patients had 5.5 times increased hazard of death (95% Cl 3.4-8.8). Nuclear myoferlin expression was also directly associated with tumor recurrence (p<0.001), perineural invasion (p=0.008), extracapsular spread (p=0.009), higher T-stage (p=0.0015) and distant metastasis (p<0.001). In addition, nuclear MYOF expression was directly associated with IL-6 (p<0.001) and inversely with HPV status (p=0.0014). In a subgroup survival analysis, MYOF nuclear+/IL-6+ group had worst survival (84.6% mortality), whereas MYOF nuclear-/IL-6- had the best survival. Similarly, patients with HPV-negative/MYOF-positive tumors had worse survival compared to HPV-positive/MYOF-negative. Taken together, our results demonstrate for the first time that nuclear myoferlin expression independently predicts poor clinical outcome in OPSCC patients.

Highlights

Head and neck squamous cell carcinoma (HNSCC) is the eighth most frequent cancer worldwide and includes the following subsites: oral cavity, nasopharynx, oropharynx, hypopharynx and larynx [1, 2]
We examined the expression of myoferlin in surgically treated oropharyngeal squamous cell carcinoma samples and correlated that with survival, human papillomavirus (HPV) status, and other clinical and pathological variables
We show that myoferlin expression, nuclear myoferlin expression, is highly predictive of poor overall survival, tumor recurrence, perineural invasion, higher T stage and distal metastasis in oropharyngeal squamous cell carcinoma (OPSCC) patients

Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC) is the eighth most frequent cancer worldwide and includes the following subsites: oral cavity, nasopharynx, oropharynx, hypopharynx and larynx [1, 2]. The majority of patients present with locally advanced stage disease and require multimodality therapy with surgery followed by chemotherapy/radiotherapy or organ preserving chemotherapy/radiotherapy [3,4,5]. These treatments are intensive and associated with severe acute toxicity, such as mucositis, dermatitis and dysphagia as well as long term sensorineural hearing loss, permanent xerostomia and altered swallowing function [6, 7]. Advancements in the anti-cancer treatments including surgery, radiation and chemotherapy have increased the local control of HNSCC, the overall survival rates have not improved significantly over the last three decades [8]. It is becoming increasing clear that treatment for patients with HNSCC has to shift from a single disease approach to tailoring the therapy based on patient’s tumor characteristics

Methods

Results

Conclusion