Profiling Invasiveness in Head and Neck Cancer: Recent Contributions of Genomic and Transcriptomic Approaches

Nisa, Lluís; Aebersold, Daniel M.; Giger, Roland; Caversaccio, Marco; Borner, Urs; Medová, Michaela; Zimmer, Yitzhak

doi:10.3390/cancers7020585

Cited by 8 publications

(7 citation statements)

References 79 publications

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“…HNSCC studies showed that the expression of uPA and uPAR is also commonly higher in tumor tissue than in normal tissue [ 114 , 115 , 117 , 119 , 127 , 133 - 137 ]. We also found similar results by analyzing the expression data (RNA seq level 3 data) of HNSCC samples included in TCGA project (Figure 3A ) Tobacco smoke could induce the expression of uPA which is commonly overexpressed in premalignant and malignant lesions in the oral cavity [ 138 ].…”

Section: Serpine1 Upa and Upar Expression As Prognostic Markers In Hmentioning

confidence: 99%

uPA/uPAR and SERPINE1 in head and neck cancer: role in tumor resistance, metastasis, prognosis and therapy

et al. 2016

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There is strong evidence supporting the role of the plasminogen activator system in head and neck squamous cell carcinoma (HNSCC), particularly of its uPA (urokinase plasminogen activator) / uPAR (urokinase plasminogen activator receptor) and SERPINE1 components. Overexpression of uPA/uPAR and SERPINE1 enhances tumor cell migration and invasion and plays a key role in metastasis development, conferring poor prognosis. The apparent paradox of uPA/uPAR and its inhibitor SERPINE1 producing similar effects is solved by the identification of SERPINE1 activated signaling pathways independent of uPA inhibition. Both uPA/uPAR and SERPINE1 are directly linked to the induction of epithelial-to-mesenchymal transition, the acquisition of stem cell properties and resistance to antitumor agents. The aim of this review is to provide insight on the deregulation of these proteins in all these processes.We also summarize their potential value as prognostic biomarkers or potential drug targets in HNSCC patients. Concomitant overexpression of uPA/uPAR and SERPINE1 is associated with a higher risk of metastasis and could be used to identify patients that would benefit from an adjuvant treatment. In the future, the specific inhibitors of uPA/uPAR and SERPINE1, which are still under development, could be used to design new therapeutic strategies in HNSCCs.

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Section: Serpine1 Upa and Upar Expression As Prognostic Markers In Hmentioning

confidence: 99%

uPA/uPAR and SERPINE1 in head and neck cancer: role in tumor resistance, metastasis, prognosis and therapy

et al. 2016

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“…[ 4 ] Infection by high-risk subtypes of human papillomavirus has also been established as an important etiologic factor that accounts for a trend for increasing the incidence of oropharyngeal cancers in men younger than age 50 years without a history of tobacco use. [ 5 6 7 8 ]…”

Section: Introductionmentioning

confidence: 99%

Sonic hedgehog in oral squamous cell carcinoma: An immunohistochemical study

Srinath

Iyengar²,

Mysorekar

2016

J Oral Maxillofac Pathol

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Background:Recent studies have revealed the involvement of hedgehog (Hh) signaling component in proliferation and invasive behavior of many carcinomas.Aim:This study aims to identify the expression of sonic Hh (SHH) protein of SHH pathway in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC) using SHH (H-160) (Santa Cruz, sc-9042) which could have therapeutic implication in future.Materials and Methods:A total of 250 cases comprising 50 normal oral mucosa, 50 cases of oral epithelial dysplasia, 50 well, 50 moderate and 50 poorly differentiated OSCCs were included in the study. Immunohistochemical evaluation of SHH protein expression was conducted using monoclonal antibody. Interpretation of the expression was done by immunoreactive score of Remmele and Stegner (IRS) scoring method.Statistical Analysis:Chi-Square test was used to analyze the results.Results:The study showed that SHH signaling molecules are highly expressed in OSCC, and their expression was mainly in the cytoplasm of epithelial cells.Conclusion:The SHH signaling component is associated with the pathological parameter in OSCC and oral epithelial dysplasia.

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“…Locoregional recurrence and metastasis are the limiting factors for successful treatments [ 43 ]. Profiling DNA methylation is a widely applied tool to identify subtypes of cancers and to predict therapy outcomes [ 44 ]. Several studies have been carried out to explore the association between changes in DNA methylation and survival of patients with hypopharynx, larynx, and oral cavity cancers [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Analysis of Site-Specific Methylation of Tumor-Related Genes in Head and Neck Cancer: Potential Utility as Biomarkers for Prognosis

Misawa

Mochizuki

Imai

et al. 2018

Cancers

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Clarifying the epigenetic regulation of tumor-related genes (TRGs) can provide insights into the mechanisms of tumorigenesis and the risk for disease recurrence in HPV-negative head and neck cancers, originating in the hypopharynx, larynx, and oral cavity. We analyzed the methylation status of the promoters of 30 TRGs in 178 HPV-negative head and neck cancer patients using a quantitative methylation-specific PCR. Promoter methylation was correlated with various clinical characteristics and patient survival. The mean number of methylated TRGs was 14.2 (range, 2–25). In the multivariate Cox proportional hazards analysis, the methylation of COL1A2 and VEGFR1 was associated with poor survival for hypopharyngeal cancer, with hazard ratios: 3.19; p = 0.009 and 3.07; p = 0.014, respectively. The methylation of p16 and COL1A2 were independent prognostic factors for poor survival in laryngeal cancer (hazard ratio: 4.55; p = 0.013 and 3.12; p = 0.035, respectively). In patients with oral cancer, the methylation of TAC1 and SSTR1 best correlated with poor survival (hazard ratio: 4.29; p = 0.005 and 5.38; p = 0.029, respectively). Our findings suggest that methylation status of TRGs could serve as important site-specific biomarkers for prediction of clinical outcomes in patients with HPV-negative head and neck cancer.

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Profiling Invasiveness in Head and Neck Cancer: Recent Contributions of Genomic and Transcriptomic Approaches

Cited by 8 publications

References 79 publications

uPA/uPAR and SERPINE1 in head and neck cancer: role in tumor resistance, metastasis, prognosis and therapy

uPA/uPAR and SERPINE1 in head and neck cancer: role in tumor resistance, metastasis, prognosis and therapy

Sonic hedgehog in oral squamous cell carcinoma: An immunohistochemical study

Analysis of Site-Specific Methylation of Tumor-Related Genes in Head and Neck Cancer: Potential Utility as Biomarkers for Prognosis

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