Bochen Florian, Adisurya Hana, Wemmert Silke, Lerner Cornelia, Greiner Markus, Zimmermann Richard, Hasenfus Andrea, Wagner Mathias, Smola Sigrun, Pfuhl Thorsten, Bozzato Alessandro, Al Kadah Basel, Schick Bernhard, Linxweiler Maximilian
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.
Oncotarget. 2017 Jan 17;8(3):4922-4934. doi: 10.18632/oncotarget.13986.
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.
3号染色体q26区域扩增是头颈部鳞状细胞癌（HNSCC）中常见的一种改变。在包括HNSCC在内的多种癌症中均检测到3q26编码基因SEC62和SOX2的过表达，这表明它们可能具有癌基因功能。在我们的研究中，我们阐明了SEC62和SOX2在HNSCC患者中的功能，主要关注它们对淋巴转移和患者生存的影响。我们分析了65例HNSCC患者和29例原发灶不明的宫颈癌（CUP）患者组织标本中SEC62和SOX2的表达；与相应的原发肿瘤相比，HNSCC患者淋巴结转移灶中SEC62表达较高，SOX2表达较低。CUP患者的淋巴结转移灶与HNSCC患者的淋巴结转移灶相比，SEC62表达较高，SOX2表达较低。从N1期进展到N3期时，淋巴结转移灶中SEC62表达增加，SOX2表达降低。此外，这两个基因作为预后生物标志物均显示出高度显著的相关性，SEC62高表达和SOX2低表达的患者预后最差。在功能分析中，敲低SEC62导致HNSCC细胞迁移受到抑制，相反，SEC62和SOX2过表达则刺激细胞迁移。综上所述，我们的研究表明，3q癌基因SEC62和SOX2的表达影响HNSCC和CUP患者的淋巴转移和细胞迁移，并且在这些疾病中具有高度的预后相关性。
