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

Bochen, Florian; Adisurya, Hana; Wemmert, Silke; Lerner, Cornelia; Greiner, Markus; Zimmermann, Richard; Hasenfus, Andrea; Wagner, Mathias; Smola, Sigrun; Pfuhl, Thorsten; Bozzato, Alessandro; Kadah, Basel Al; Schick, Bernhard; Linxweiler, Maximilian

doi:10.18632/oncotarget.13986

Cited by 33 publications

(60 citation statements)

References 48 publications

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“…High SEC. 62 and low SOX2 expression of chromosome 3q26-encoded genes were related to lymph node metastasis and worse prognosis in HNSCC and cervical cancer of unknown primary patients 25 . In this study, patients with high mRNA expression had a better prognosis than those with low mRNA expression (p = 0.0368) (Supplementary Fig.…”

Section: Discussionmentioning

confidence: 93%

SOX2 activation predicts prognosis in patients with head and neck squamous cell carcinoma

Chung

Jung

et al. 2018

Sci Rep

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SOX2 copy number and mRNA expression were analysed to examine the clinical significance of SOX2 activation in HNSCC. Gene expression signatures reflecting SOX2 activation were identified in an HNSCC cohort. Patients with HNSCC were classified into two subgroups according to the gene expression signature: SOX2-high and SOX2-low. The clinical significance of SOX2 activation was further validated in two independent cohorts. Moreover, clinical significance of SOX2 activation in response to radiotherapy was assessed in patients with HNSCC. The relationship between SOX2 activation and radiotherapy was validated in an in vitro experiment. Patients in the SOX2-high subgroup had a better prognosis than patients in the SOX2-low subgroup in all three patient cohorts. Results of multivariate regression analysis showed that SOX2 signature was an independent predictor of the overall survival of patients with HNSCC (hazard ratio, 1.45; 95% confidence interval, 1.09–1.92; P = 0.01). Interestingly, SOX2 activation was a predictor of therapy outcomes in patients receiving radiotherapy. Moreover, SOX2 overexpression enhanced the effect of radiotherapy in HNSCC cell lines. SOX2 activation is associated with improved prognosis of patients with HNSCC and might be used to predict which patients might benefit from radiotherapy.

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Section: Discussionmentioning

confidence: 93%

SOX2 activation predicts prognosis in patients with head and neck squamous cell carcinoma

Chung

Jung

et al. 2018

Sci Rep

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“…and Bochen et al . reported on a positive prognostic value of high-level expression of Sox2 in HNSCC 44 , 45 . However, contradicting results have been reported too, such that HNSCC patients with high-level Sox2 expression were characterized by poorer outcome 46 , as well as a complete lack of prognostic value of Sox2 in HNSCC 47 .…”

Section: Discussionmentioning

confidence: 99%

High Expression of EpCAM and Sox2 is a Positive Prognosticator of Clinical Outcome for Head and Neck Carcinoma

Baumeister

Hollmann

Kitz

et al. 2018

Sci Rep

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Locally advanced head and neck squamous cell carcinomas (HNSCC) have limited prognosis due to frequent treatment failure. Currently, TNM-classification and human papillomavirus (HPV) infection are the sole clinical prognosticators of outcome. Tumor heterogeneity and stemness based on epithelial-mesenchymal-transition reportedly associate with therapy resistance. The capacity of epithelial marker EpCAM (EpEX), stemness regulator Sox2 and mesenchymal marker vimentin to predict clinical outcome of HSNCC patients was assessed upon immunohistochemistry staining in two cohorts of HNSCC patients treated with surgery and adjuvant radio (chemo) therapy (n = 94) and primary radio (chemo) therapy (n = 94), respectively. Prognostic values with respect to overall, disease-free and disease-specific survival were assessed in uni- and multivariate cox proportional hazard models to generate integrated risk scores. EpEX, Sox2 and vimentin displayed substantial inter- and intratumoral heterogeneity. EpEXhigh and Sox2high predicted improved clinical outcome in the discovery cohort and in the HPV-negative sub-cohort. EpEXhigh and Sox2high were confirmed as prognosticators of clinical outcome in the validation cohort treated with definitive radio(chemo)therapy. Importantly, EpEXhigh identified patients with improved survival within the HPV-negative subgroup of the validation cohort. Hence, Sox2high and particularly EpEXhigh have potential as tools to predict clinical performance of HNSCC patients, foremost HPV-negative cases, in the frame of molecular-guided treatment decision-making.

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“…Recently, two studies reported that high expression level of Sox2 in head and neck squamous cell carcinomas (HNSCC) had beneficial effect on patient survival [ 23 , 24 ]. Since HNSCC is from squamous cells, while CRC belongs to adenocarcinoma, we speculate that same gene in different kinds of tumor or under different genetic background might play different roles.…”

Section: Discussionmentioning

confidence: 99%

Sox2 modulates motility and enhances progression of colorectal cancer via the Rho-ROCK signaling pathway

Zheng

Pan

et al. 2017

Oncotarget

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Sox2 (Sry-box2) is essential for a variety of stem cells and is also expressed in colorectal cancer (CRC). However, the underlying mechanism by which Sox2 enhances CRC progression remains unclear. In the present study, we show that elevated Sox2 expression is significantly correlated with poor clinical prognosis. CRC is phenotypically heterogeneous, and harbors several subtypes of cancer cells. Elevated Sox2 expression was always detected in rounded-shape cells, which co-located to poorly differentiated regions, the invasive frontier and metastatic lesions. Knockdown of Sox2 in CRC cells not only decreased the number of round-shaped cells, but also suppressed cell migration, invasion as well as attenuated colony forming capacity and tumorigenicity. By contrast, overexpression of Sox2 in CRC cells was associated with up-regulation of multidrug resistance genes and accelerated CRC progression. Moreover, Sox2 conferred activation of Rho-ROCK signaling, whereas inhibition of ROCK signaling decreased cell migration, invasion, colony formation and self-renewal of CRC. Our results reveal that CRC is phenotypically and functionally heterogeneous. Elevated Sox2 expression activates the Rho-ROCK pathway, which in turn changes cell morphology and promotes cell migration and progression.

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

Cited by 33 publications

References 48 publications

SOX2 activation predicts prognosis in patients with head and neck squamous cell carcinoma

SOX2 activation predicts prognosis in patients with head and neck squamous cell carcinoma

High Expression of EpCAM and Sox2 is a Positive Prognosticator of Clinical Outcome for Head and Neck Carcinoma

Sox2 modulates motility and enhances progression of colorectal cancer via the Rho-ROCK signaling pathway

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