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.
Highlights
Head and neck squamous cell carcinomas (HNSCCs) account for 5% of all human malignancies and are associated with a constantly poor prognosis for many years [1]
Our study showed that the expression of the 3q oncogenes SEC62 and SOX2 affects lymphatic metastasis and cell migration in head and neck squamous cell carcinomas (HNSCCs) and cancer of unknown primary (CUP) patients and has a high prognostic relevance in these diseases
The effects of nicotine and alcohol consumption [6, 7], as well as infection of the oral mucosa with high-risk human papillomavirus [8], on the carcinogenesis of HNSCCs have been well known for many years, it is still not completely known which molecular processes drive the malignant transformation in these diseases and which differences in tumor cell biology are responsible for the different clinical phenotypes of HNSCCs compared with CUP syndrome [4, 7, 9, 10]
Summary
Head and neck squamous cell carcinomas (HNSCCs) account for 5% of all human malignancies and are associated with a constantly poor prognosis for many years [1]. Compared with SEC62, SOX2 seems to affect the migration and metastasis of cancer cells; an analysis of SOX2 expression in HNSCC tissue specimens showed a significant correlation with positive lymph node status, [38] and artificial SOX2 overexpression in laryngeal cancer cells stimulated their migratory potential [39, 40]. Other studies have shown a correlation between high SOX2 expression and negative lymph node status in HNSCC patients [41, 42], as well as a favorable prognosis in NSCLC [43], gastric cancer [44] and HNSCC patients [42]. We analyzed the expression level of both genes in lymph node metastases from HNSCC and CUP syndrome patients and performed functional analyses to delineate the effect of SEC62 and SOX2 on the proliferation and migration of HNSCC cells, respectively
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