title: High expression of myoferlin is associated with poor outcome in oropharyngeal squamous cell carcinoma patients and is inversely associated with HPV-status.
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.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The Ohio State University, Columbus, OH 43210, USA.|Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Bhavna
authors.initials: B
authors.lastname: Kumar
authors.affiliation: Center for Biostatistics, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Nicole V
authors.initials: NV
authors.lastname: Brown
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Swanson
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH 43210, USA.|Current affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30303, USA.
authors.forename: Alessandra C
authors.initials: AC
authors.lastname: Schmitt
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The Ohio State University, Columbus, OH 43210, USA.|Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Old
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The Ohio State University, Columbus, OH 43210, USA.|Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Enver
authors.initials: E
authors.lastname: Ozer
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The Ohio State University, Columbus, OH 43210, USA.|Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Agrawal
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The Ohio State University, Columbus, OH 43210, USA.|Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Schuller
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The Ohio State University, Columbus, OH 43210, USA.|Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Theodoros N
authors.initials: TN
authors.lastname: Teknos
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The Ohio State University, Columbus, OH 43210, USA.|Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Pawan
authors.initials: P
authors.lastname: Kumar
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D052162:Human papillomavirus 16 / Q000302:isolation & purification*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D000071317:Nanog Homeobox Protein / Q000096:biosynthesis / Q000235:genetics; D009959:Oropharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D011379:Prognosis; D000077195:Squamous Cell Carcinoma of Head and Neck; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D015850:Interleukin-6; C415584:MYOF protein, human; D008565:Membrane Proteins; D009124:Muscle Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein
keywords: HPV; IL-6; OPSCC; myoferlin; nanog