title: Effect of 3q oncogenes SEC62 and SOX2 on lymphatic metastasis and clinical outcome of head and neck squamous cell carcinomas.
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.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Saarland University Medical Center, Homburg (Saar), Germany.|Institute of Medical Biochemistry and Molecular Biology, Saarland University Medical Center, Homburg (Saar), Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Bochen
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Saarland University Medical Center, Homburg (Saar), Germany.
authors.forename: Hana
authors.initials: H
authors.lastname: Adisurya
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Saarland University Medical Center, Homburg (Saar), Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Wemmert
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Saarland University Medical Center, Homburg (Saar), Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Lerner
authors.affiliation: Institute of Medical Biochemistry and Molecular Biology, Saarland University Medical Center, Homburg (Saar), Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Greiner
authors.affiliation: Institute of Medical Biochemistry and Molecular Biology, Saarland University Medical Center, Homburg (Saar), Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Zimmermann
authors.affiliation: Department of General and Surgical Pathology, Saarland University Medical Center, Homburg (Saar), Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hasenfus
authors.affiliation: Department of General and Surgical Pathology, Saarland University Medical Center, Homburg (Saar), Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Wagner
authors.affiliation: Institute of Virology, Saarland University Medical Center, Homburg (Saar), Germany.
authors.forename: Sigrun
authors.initials: S
authors.lastname: Smola
authors.affiliation: Institute of Virology, Saarland University Medical Center, Homburg (Saar), Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Pfuhl
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Saarland University Medical Center, Homburg (Saar), Germany.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bozzato
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Saarland University Medical Center, Homburg (Saar), Germany.
authors.forename: Basel
authors.initials: B
authors.lastname: Al Kadah
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Saarland University Medical Center, Homburg (Saar), Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schick
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Saarland University Medical Center, Homburg (Saar), Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Linxweiler
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000077195:Squamous Cell Carcinoma of Head and Neck; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D026901:Membrane Transport Proteins; C103676:SEC62 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors
keywords: 3q amplification; SEC62; SOX2; head and neck cancer; prognostic biomarkers