scholarly journals Potential Roles of Cornichon Family AMPA Receptor Auxiliary Protein 4 (CNIH4) in Head and Neck Squamous Cell Carcinoma

Author(s):  
Yixue Li ◽  
Hengrui Liu ◽  
Yue Han

Abstract Background The diagnosis and prognosis of neck squamous cell carcinoma (HNSC) is a challenge for clinical HNSC management, thus, the investigation of molecular biomarkers of HNSC is urgent. We hypothesized that Cornichon Family AMPA Receptor Auxiliary Protein 4 (CNIH4) is a biomarker for HNSC.Methods We analyzed mRNA seq data, protein staining data, and single-cell expression data of HNSC from open databases and evaluated the diagnostic and prognostic value of CNIH4, and investigated the association of CNIH4 to HNSC cancer biology and immunity.Results CNIH4 was expressed higher and have higher copy number in HNSC compared to normal tissues. CNIH4 was associated with worse overall survival of HNSC patients. A survival nomogram was constructed. 2012 and 421genes were identified as positively and negatively associated with CNIH4 respectively, and they were enriched in “Cell cycle”, “DNA replicate”, “Cytokine−cytokine receptor interaction”, etc. CNIH4 was positively correlated with “stemness”, “cell cycle”, and “DNA repair” in single-cell data. CNIH4 was potentially associated with changes in multiple immune cell infiltration and cancer immune escape. Conclusion CNIH4 is a diagnostic and prognostic biomarker for HNSC patients and can potentially affect the cancer stemness and tumor immune microenvironment of HNSC cells.

Oncotarget ◽  
2017 ◽  
Vol 8 (42) ◽  
pp. 73208-73218 ◽  
Author(s):  
Andres Stucky ◽  
Parish P. Sedghizadeh ◽  
Susan Mahabady ◽  
Xuelian Chen ◽  
Cheng Zhang ◽  
...  

2017 ◽  
Vol 392 ◽  
pp. 71-82 ◽  
Author(s):  
Ming Zhang ◽  
Ratnakar Singh ◽  
Shaohua Peng ◽  
Tuhina Mazumdar ◽  
Vaishnavi Sambandam ◽  
...  

2021 ◽  
Author(s):  
Katie E. Blise ◽  
Shamilene Sivagnanam ◽  
Grace L. Banik ◽  
Lisa M. Coussens ◽  
Jeremy Goecks

ABSTRACTRecent research has provided compelling evidence that the spatial organization of cells within the tumor-immune microenvironment (TiME) of solid tumors correlates with survival and response to therapy in numerous cancer types. Here, we report results of a quantitative single-cell spatial analysis of the TiME of primary and recurrent human head and neck squamous cell carcinoma (HNSCC) tumors, that builds upon our initial longitudinal study of these same HNSCCs that annotated immune complexity at near single cell resolution. Herein, we extended multiple spatial algorithms to quantify spatial landscapes of immune cells within TiMEs. Most notably, we report that spatial compartmentalization, rather than mixing, between neoplastic tumor cells and immune cells is associated with longer patient survival, as well as revealing mesenchymal spatial cellular neighborhoods and their association with improved patient outcomes. Results reported herein are concordant with studies in other tumor types, thus indicating that cellular heterogeneity within tumors trends with spatial TiME features, and are likely prognostic for patient survival.


Author(s):  
Bernhard J. Jank ◽  
Teresa Lenz ◽  
Markus Haas ◽  
Lorenz Kadletz-Wanke ◽  
Nicholas J. Campion ◽  
...  

SummaryBackground. Resistance to radiation therapy poses a major clinical problem for patients suffering from head and neck squamous cell carcinoma (HNSCC). Transforming growth factor ß (TGF-ß) has emerged as a potential target. This study aimed to investigate the radiosensitizing effect of galunisertib, a small molecule TGF-ß receptor kinase I inhibitor, on HNSCC cells in vitro. Methods. Three HNSCC cell lines were treated with galunisertib alone, or in combination with radiation. Of those three cell lines, one has a known inactivating mutation of the TGF-ß pathway (Cal27), one has a TGF-ß pathway deficiency (FaDu) and one has no known alteration (SCC-25). The effect on metabolic activity was evaluated by a resazurin-based reduction assay. Cell migration was evaluated by wound-healing assay, clonogenic survival by colony formation assay and cell cycle by FACS analysis. Results. Galunisertib reduced metabolic activity in FaDu, increased in SCC-25 and had no effect on CAL27. Migration was significantly reduced by galunisertib in all three cell lines and showed additive effects in combination with radiation in CAL27 and SCC-25. Colony-forming capabilities were reduced in SCC-25 by galunisertib and also showed an additive effect with adjuvant radiation treatment. Cell cycle analysis showed a reduction of cells in G1 phase in response to galunisertib treatment. Conclusion. Our results indicate a potential antineoplastic effect of galunisertib in HNSCC with intact TGF-ß signaling in combination with radiation.


2019 ◽  
Vol 3 (4) ◽  
Author(s):  
Paul Gougis ◽  
Camille Moreau Bachelard ◽  
Maud Kamal ◽  
Hui K Gan ◽  
Edith Borcoman ◽  
...  

Abstract A better understanding of cancer biology has led to the development of molecular targeted therapy, which has dramatically improved the outcome of some cancer patients, especially when a biomarker of efficacy has been used for patients’ selection. In head and neck oncology, cetuximab that targets epidermal growth factor receptor is the only targeted therapy that demonstrated a survival benefit, both in the recurrent and in the locally advanced settings, yet without prior patients’ selection. We herein review the clinical development of targeted therapy in head and neck squamous cell carcinoma in light of the molecular landscape and give insights in on how innovative clinical trial designs may speed up biomarker discovery and deployment of new molecular targeted therapies. Given the recent approval of immune checkpoint inhibitors targeting programmed cell death-1 in head and neck squamous cell carcinoma, it remains to be determined how targeted therapy will be incorporated into a global drug development strategy that will inevitably incorporate immunotherapy.


Author(s):  
Yi Ding ◽  
Min Li ◽  
Tuersong Tayier ◽  
Long Chen ◽  
ShuMei Feng

Background: : Head and neck squamous cell carcinoma (HNSCC) is a common cancer that is characterized by a complex pathogenesis. Only limited data are available on the primary pathogenic genes and pathways in HNSCC. Objective: This study aimed to identify potential biomarkers of HNSCC and explore its underlying mechanisms. Methods: We screened differentially expressed genes (DEGs) using the Gene Expression Omnibus(GEO) database. Gene Ontology (GO) and Reactome pathway enrichment were analyzed using the STRING database. The protein-protein interaction network of the DEGs was reconstructed using Cytoscape software in STRING. The ONCOMINE and UNLCAN databases were used to identify the expression of hub genes. In addition, we employed UNLCAN to correlate tumor grade with key genes. Results: Finally, the effect of hub genes on overall survival (OS) was analyzed using the Kaplan-Meier method. In total, 22 DEGs were identified, These were related to the mitotic cell cycle, mitotic G1-G1, and S phases, G2/M transition, NOTCH signaling, and regulation of TP53 activity. Seven hub genes were screened with Cytoscape. Increased expression of five hub genes (AURKA, BIRC5, MKI67, UBE2C, and TOP2A) was related to a higher tumor grade and worse OS. Conclusion: We have identified five key genes that may help us understand the carcinogenic mechanisms related to the cell cycle in HNSCC. These genes may be used as biomarkers for survival and treatment of HNSCC.


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