Effect of 3q oncogenes SEC62 and SOX2 on lymphatic metastasis and clinical outcome of head and neck squamous cell carcinomas
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Florian Bochen1,2,*, Hana Adisurya1,*, Silke Wemmert1, Cornelia Lerner1, Markus Greiner2, Richard Zimmermann2, Andrea Hasenfus3, Mathias Wagner3, Sigrun Smola4, Thorsten Pfuhl4, Alessandro Bozzato1, Basel Al Kadah1, Bernhard Schick1, Maximilian Linxweiler1
1Department of Otorhinolaryngology, Head and Neck Surgery, Saarland University Medical Center, Homburg (Saar), Germany
2Institute of Medical Biochemistry and Molecular Biology, Saarland University Medical Center, Homburg (Saar), Germany
3Department of General and Surgical Pathology, Saarland University Medical Center, Homburg (Saar), Germany
4Institute of Virology, Saarland University Medical Center, Homburg (Saar), Germany
*These authors contributed equally to this work
Maximilian Linxweiler, email: firstname.lastname@example.org
Keywords: head and neck cancer, 3q amplification, SEC62, SOX2, prognostic biomarkers
Received: June 21, 2016 Accepted: December 05, 2016 Published: December 16, 2016
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.
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