scholarly journals VAV2 signaling promotes regenerative proliferation in both cutaneous and head and neck squamous cell carcinoma

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
L. Francisco Lorenzo-Martín ◽  
Natalia Fernández-Parejo ◽  
Mauricio Menacho-Márquez ◽  
Sonia Rodríguez-Fdez ◽  
Javier Robles-Valero ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Rho Gtpase ◽  
Neck Squamous Cell Carcinoma ◽  
Proliferation Capacity ◽  
Poor Differentiation ◽  
Patient Prognosis ◽  
Hnscc Patient

Abstract Regenerative proliferation capacity and poor differentiation are histological features usually linked to poor prognosis in head and neck squamous cell carcinoma (hnSCC). However, the pathways that regulate them remain ill-characterized. Here, we show that those traits can be triggered by the RHO GTPase activator VAV2 in keratinocytes present in the skin and oral mucosa. VAV2 is also required to maintain those traits in hnSCC patient-derived cells. This function, which is both catalysis- and RHO GTPase-dependent, is mediated by c-Myc- and YAP/TAZ-dependent transcriptomal programs associated with regenerative proliferation and cell undifferentiation, respectively. High levels of VAV2 transcripts and VAV2-regulated gene signatures are both associated with poor hnSCC patient prognosis. These results unveil a druggable pathway linked to the malignancy of specific SCC subtypes.

S146 – COX-2 & IL-10 Polymorphisms with Head and Neck Carcinoma

2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P125-P125
Author(s):  
Seung-Won Jeong ◽  
Kang Seokyoung ◽  
Kim Hee-Ok ◽  
Seok Hyun Cho ◽  
Kyung-Rae Kim ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Patient Group ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Korean Population ◽  
Healthy Controls ◽  
Cox 2 ◽  
Hnscc Patient

Objectives The objectives of this study are to investigate the frequencies of single nucleotide polymorphism (SNP) of COX-2 and IL-10 in control group and the head and neck squamous cell carcinoma (HNSCC) patient group in Korean population and to analyze the correlation of COX-2 (−1329A>G, + 1266C>T, +6365T>C) and IL-10(−1082A>G, +920T>G, +3917T>C) polymorphisms of HNSCC patient group in Korean population. Methods Study was performed for 290 Korean head and neck squamous cell carcinoma patients and 358 healthy controls. DNA extraction of peripheral whole blood was done and genotyping was done by single base extension(SBE) and Taq-Man assay. We analyze the frequencies of SNP of cox-2(−1329A>G, +1266C>T, +6365T>C) and IL-10(−1082A>G, +920T>G, +3917T⋉C) and the following results were obtained. Results There is no statistical difference between carcinoma patients and healthy controls about frequencies of SNP of cox-2(−1329A>G, +1266C>T, +6365T>C) and IL-10 (−1082A>G, +920T>G, +3917T>C) except haplotype3(-/-, ht3/-, ht3/ht3) of COX-2 (−1329A>G, +1266C>T, +6365T>C) (Odds ratio: 0.60, p value: 0.03) in Korean populations. Conclusions Based on these results, it is suggested that COX-2(−1329A>G, +1266C>T, +6365T>C), IL-10 (−1082A>G, +920T>G, +3917T>C) genetic polymorphisms might not be correlated with head and neck squamous cell carcinoma in Korean populations but haplotype3 (ht3) of COX-2 might be associated with HNSCC.

scholarly journals Development of a Prognostic Pyroptosis-Related Gene Signature for Head and Neck Squamous Cell Carcinoma Patient

2021 ◽  
Author(s):  
Weiwen Zhu ◽  
Jiayi Zhang ◽  
Mengyao Wang ◽  
Rundong Zhai ◽  
Yanbin Xu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Death ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Patient Outcomes ◽  
Squamous Cell ◽  
Gene Signature ◽  
Related Gene ◽  
Patient Prognosis ◽  
Hnscc Patient

Abstract Objective: Head and neck squamous cell carcinoma (HNSCC) is a major threat to public health. Pyroptosis is a form of inflammatory programmed cell death that is still incompletely understood. The role of pyroptotic cell death in HNSCC remains to be fully defined. As such, the present study was developed to explore the potential prognostic utility of a pyroptosis-related gene (PRG) signature in HNSCC.Methods: PRG expression patterns and the associated mutational landscape in HNSCC were analyzed, after which a 6-gene prognostic model was constructed through least absolute shrinkage and selection operator (LASSO) and Cox regression analyses using the TCGA dataset, followed by validation with two GEO datasets (GSE41643 and GSE65858). Potential predictors of patient outcomes associated with this 6-gene model were identified through topological degree analyses of a protein-protein interaction network. Lastly, the prognostic value of NLRP3 as a predictor of HNSCC patient prognosis was established through immunohistochemical (IHC) analyses of samples from 176 HNSCC patients.Results: Differentially expressed PRGs were able to readily differentiate between HNSCC tumors and normal tissues. Risk scores derived from the 6-gene PRG model were independent predictors of HNSCC patient prognosis, and genes that were differentially expressed between low- and high-risk groups were associated with tumor immunity. IHC analyses further supported the value of NLRP3 as a predictor of HNSCC patient outcomes. Conclusions: Overall, these results highlight a novel prognostic gene signature that offers value in the context of HNSCC patient evaluation, although additional research will be essential to elucidate the mechanisms linking these PRGs to HNSCC outcomes.

scholarly journals Multi-Omics Integrative Analysis Identifying EPC1 as a Prognostic Biomarker in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Yongmei Dai ◽  
Wenhan chen ◽  
Junpeng Huang ◽  
Tongjian Cui ◽  
chen huang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Protective Factor ◽  
Prognostic Significance ◽  
Endocrine Resistance ◽  
Neck Squamous Cell Carcinoma ◽  
Multiple Cancer ◽  
Patient Prognosis

Abstract Background: To investigate the prognostic significance and related mechanisms of the expression of enhancer of polycomb homolog 1 ( EPC1 ) in head and neck squamous cell carcinoma (HNSCC) from a multi-omics perspective. Methods: The Kaplan-Meier plotter was used to evaluate the prognostic significance of EPC1 . Based on the LinkedOmics, UALCAN, and Timer platforms, the multi-omics expression of EPC1 in HNSCC was explored to investigate mechanisms affecting prognoses. Results: At the genetic level, 8208 genes were negatively correlated with EPC1 expression, and 11,956 genes were positively correlated with EPC1 expression. For the noncoding region, a competing endogenous RNA (ceRNA) network was constructed, and 6 microRNAs (miRNAs) and 3 long noncoding RNAs (lncRNAs) were identified. At the protein level, a protein-protein interaction (PPI) network related to EPC1 expression was constructed and was involved in human papillomavirus (HPV) infection, endocrine resistance, and multiple cancer pathways. At the immune level, EPC1 expression was correlated with a variety of immune cells, immune molecules, and chemokine receptors, which together constitute the immune microenvironment of tumors. According to the clinical data, high EPC1 expression in HNSCC was a predictor of patient prognosis (hazard ratio (HR)=0.64; 95% confidence interval (CI) 0.49-0.83; P<0.01). EPC1 expression differentiated clinical subtypes and was related to key factors such as TP53 and HPV (P<0.05). Conclusion: High EPC1 expression is a protective factor in HNSCC and benefits patient survival. EPC1 may participate in the genomics, transcriptomics, proteomics, and immunomics of HNSCC, and the results can provide a reference for the development of targeted drugs and the evaluation of patient prognosis.

scholarly journals MAGE-A11 Expression Predicts Patient Prognosis in Head and Neck Squamous Cell Carcinoma

2020 ◽  
Vol Volume 12 ◽  
pp. 1427-1435 ◽  
Author(s):  
Shiheng Jia ◽  
Minghui Zhang ◽  
Yanshu Li ◽  
Lan Zhang ◽  
Wei Dai
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Patient Prognosis

Hubungan ekspresi p53, Bcl-2, c-Myc dan MMP-9 dengan gambaran klinikopatologi karsinoma sel skuamosa kepala-leher

2016 ◽  
Vol 46 (1) ◽  
pp. 53
Author(s):  
Azwar Azwar ◽  
Sofia Mubarika ◽  
Agus Surono
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Tumor Location ◽  
Neck Squamous Cell Carcinoma ◽  
Second Primary ◽  
Cross Sectional ◽  
P53 Expression ◽  
Local Metastasis

Latar belakang: Karsinoma sel skuamosa kepala dan leher merupakan salah satu kanker terseringdi seluruh dunia. Pendekatan pengobatan agresif dan multidisiplin telah dilakukan, namun belum adapeningkatan yang signifikan dalam kelangsungan hidup 5 tahun, selama 20 tahun terakhir. Kegagalanpengobatan terjadi dalam bentuk kekambuhan lokoregional, metastasis jauh, dan/atau tumor primer kedua.Berbagai penanda molekular tumor telah diteliti untuk mengetahui potensinya dalam memprediksi hasilpenyakit atau respon terhadap terapi.Tujuan: Mengetahui hubungan ekspresi protein p53, Bcl-2, c-Myc,dan MMP-9 berdasarkan gambaran klinikopatologis karsinoma sel skuamosa kepala dan leher di RumahSakit dr. Zainoel Abidin.Metode: Studi menggunakan desain cross sectional. Sampel terdiri dari 60blok parafin karsinoma sel skuamosa kepala dan leher. Prosedur pewarnaan imunohistokimia dilakukandengan menggunakan antibodi monoklonal terhadap p53, Bcl-2, c-Myc, dan MMP-9. Ekspresi proteinp53, Bcl-2, c-Myc, dan MMP-9 dianalisis secara imunohistokimia pada karsinoma sel skuamosa kepaladan leher kemudian hasilnya dihubungkan dengan parameter klinikopatologis seperti usia, jenis kelamin,lokasi tumor, diferensiasi tumor, metastasis kelenjar getah bening dan stadium tumor, kemudian dianalisisstatistik dengan Chi square.Hasil: Hasil penelitian menunjukkan terdapat hubungan bermakna tingkatekspresi p53 dengan metastasis lokal (p=0,021) dan ada hubungan bermakna tingkat ekspresi MMP-9dengan lokasi tumor (p=0,026). Tidak terdapat hubungan ekspresi p53, Bcl-2, cMyc, dan MMP-9 terhadapusia, jenis kelamin, stadium tumor, diferensiasi histologi, tingkat T, N, dan metastasis jauh.Kesimpulan:Ada hubungan ekpresi p53 dengan metastasis kelenjar limfe regional dan ekspresi MMP-9 dengan lokasitumor pada karsinoma sel skuamosa kepala dan leher. Kata kunci: Karsinoma sel skuamosa kepala dan leher, p53, Bcl-2, c-Myc, MMP-9 ABSTRACTBackground: Head and neck squamous cell carcinoma (HNSCC) is one of the most commoncancers world wide. Although aggressive and multidisciplinary approach to the treatment has been done,there is no significant improvement in 5-year survival in the last 20 years. Treatment failure occurredin the form of locoregional recurrence, distant metastasis, and/or a second primary tumor. A variety oftumor molecular markers have been studied to determine their potential in predicting disease outcome orresponse to the therapy. Purpose: To investigate correlation p53, Bcl-2, c-Myc, and MMP-9 expressionto clinicopathologic parameter in head and neck squamous cell carcinoma patient in dr. Zainoel Abidinhospital. Methods: Cross sectional design study. The sample was consisted of 60 paraffin blocks ofhead and neck squamous cell carcinoma. Procedure of immunohistochemical staining used monoclonalantibodies against p53, Bcl-2, c-Myc, and MMP-9. Expression of p53 protein, Bcl-2, c-Myc, and MMP-9were analyzed by immunohistochemistry in head and neck squamous cell carcinoma. Then, the results were linked to clinicopathologic parameters such as age, sex, tumor location, tumor differentiation,lymph node metastasis and tumor stage, and statistically analyzed with Chi square. Results: The resultsshowed there were significant correlation between p53 expression level with local metastasis (p=0,021)and significant correlation of MMP-9 expression levels with tumor location (p=0,026). There were norelationship of p53, Bcl-2, cMyc and MMP-9 expressions based on age, sex, stage tumor, histologicdifferentiation, level of T, N, and distant metastases. Conclusion: There were relationships between p53expression with local metastasis and MMP-9 expression with tumor location in head and neck squamouscell carcinoma. Keywords: Head and neck squamous cell carcinoma, p53, Bcl-2, c-Myc, MMP-9

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