Effect of 3q oncogenes SEC62 and SOX2 on lymphatic metastasis and clinical outcome of head and neck squamous cell carcinomas

// Florian Bochen 1, 2, * , Hana Adisurya 1, * , Silke Wemmert 1 , Cornelia Lerner 1 , Markus Greiner 2 , Richard Zimmermann 2 , Andrea Hasenfus 3 , Mathias Wagner 3 , Sigrun Smola 4 , Thorsten Pfuhl 4 , Alessandro Bozzato 1 , Basel Al Kadah 1 , Bernhard Schick 1 , Maximilian Linxweiler 1 1 Department of Otorhinolaryngology, Head and Neck Surgery, Saarland University Medical Center, Homburg (Saar), Germany 2 Institute of Medical Biochemistry and Molecular Biology, Saarland University Medical Center, Homburg (Saar), Germany 3 Department of General and Surgical Pathology, Saarland University Medical Center, Homburg (Saar), Germany 4 Institute of Virology, Saarland University Medical Center, Homburg (Saar), Germany * These authors contributed equally to this work Correspondence to: Maximilian Linxweiler, email: maximilian.linxweiler@uks.eu Keywords: head and neck cancer, 3q amplification, SEC62, SOX2, prognostic biomarkers Received: June 21, 2016      Accepted: December 05, 2016      Published: December 16, 2016 ABSTRACT Chromosome 3q26 amplification represents a frequent alteration in head and neck squamous cell carcinomas (HNSCCs). Overexpression of 3q26 encoded genes SEC62 and SOX2 was detected in various cancers, including HNSCCs, indicating their potential function as oncogenes. In our study, we elucidated the function of SEC62 and SOX2 in HNSCC patients, with a main focus on their effect on lymphatic metastasis and patient survival. We analyzed SEC62 and SOX2 expression in tissue specimens from 65 HNSCC patients and 29 patients with cervical cancer of unknown primary (CUP); a higher SEC62 and lower SOX2 expression was observed in the lymph node metastases from HNSCC patients compared with the respective primary tumor. Lymph node metastases from CUP patients showed higher SEC62 and lower SOX2 expression compared with lymph node metastases from HNSCC patients. When proceeding from the N1 to the N3 stage, SEC62 expression in the lymph node metastases showed an increase and SOX2 expression showed a decrease. Moreover, both genes showed a highly significant relevance as prognostic biomarkers, with the worst prognosis for patients with high SEC62 and low SOX2 expression levels. In functional analyses, knockdown of SEC62 resulted in an inhibition of HNSCC cell migration while, conversely, SEC62 and SOX2 overexpression stimulated cell migration. Taken together, our study showed that the expression of the 3q oncogenes SEC62 and SOX2 affects lymphatic metastasis and cell migration in HNSCC and CUP patients and has a high prognostic relevance in these diseases.