High expression of myoferlin is associated with poor outcome in oropharyngeal squamous cell carcinoma patients and is inversely associated with HPV-status
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Bhavna Kumar1,2, Nicole V. Brown3, Benjamin J. Swanson4, Alessandra C. Schmitt4,5, Matthew Old1,2, Enver Ozer1,2, Amit Agrawal1,2, David E. Schuller1,2, Theodoros N. Teknos1,2, Pawan Kumar1,2
1Department of Otolaryngology-Head and Neck Surgery, The Ohio State University, Columbus, OH 43210, USA
2Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA
3Center for Biostatistics, The Ohio State University, Columbus, OH 43210, USA
4Department of Pathology, The Ohio State University, Columbus, OH 43210, USA
5Current affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30303, USA
Pawan Kumar, e-mail: Pawan.Kumar@osumc.edu
Keywords: myoferlin, OPSCC, HPV, IL-6, nanog
Received: December 22, 2015 Accepted: February 11, 2016 Published: February 23, 2016
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.
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