scholarly journals Identification of a minimal biomarker profile in head-and-neck squamous cell carcinoma tumors

2021 ◽  
Author(s):  
Laura Sanchez-Diaz ◽  
Lola E Navas ◽  
Elisa Suarez-Martinez ◽  
Blanca Felipe-Abrio ◽  
Ceres Fernandez-Rozadilla ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Patient Survival ◽  
Embryonic Stem ◽  
Neck Squamous Cell Carcinoma ◽  
Cytokine Signaling ◽  
Transcriptional Targets

Although important advances have been made in the knowledge of the molecular mechanisms leading to the development, of head and neck squamous cell carcinoma (HNSCC), only PDL1 is used for the immunotherapy (pemborlizumab) treatment in the first line of metastatic or recurrent disease. There are no other molecular bio-markers currently used in clinical practice. The objective of the study was to identify transcriptional alterations in patients with oral cavity cancer that identify gene networks responsible for resistance to treatment and prognosis. To identify possible targets for the treatment or prevention of these tumors, we screened for changes in transcription of genes that were recurrently altered in patients and that successfully stratify tumoral and non-tumoral samples, as well as patient survival, based on expression levels. The gene panels are primarily related to the cell cycle, DNA damage response, cytokine signaling and the immune system but also to the embryonic stem cell core. Validation of these panels in an independent cohort led to the identification of three non-interconnected genes, WDR66, SERPINH1 and ZNF622, that can predict patient survival and are differentially expressed in 3D cultures from HNSCC primary cell lines. These genes are related to stemness phenotype are transcriptional targets of the pluripotency transcription factors Sox2 and c-Myc. Our results suggest that WDR66, SERPINH1 and ZNF622 constitute a minimal signature of stemness transcriptional targets able to predict the prognosis of HNSCC tumors.

Osimertinib and dihydroartemisinin: A novel drug combination targeting head and neck squamous cell carcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17526-e17526
Author(s):  
Rafael Rosell ◽  
Imane Chaib ◽  
Xueting Cai ◽  
David Llige ◽  
Mariacarmela Santarpia ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Neck Squamous Cell Carcinoma ◽  
Signal Pathways ◽  
Synergistic Cytotoxicity

e17526 Background: Recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) has a dismal prognosis with limited progression-free survival and overall survival, even when treated with different combinations of chemotherapy, targeted therapies and immunotherapy. We explored in vitro and in vivo the effect of the epidermal growth factor (EGFR) inhibitor, osimertinib, alone and in combination with dihydroartemisinin (DHA) in HNSCC. Methods: The combination of osimertinib with DHA was tested in the FaDu and CAL27 HNSCC cell lines. Tumor cell proliferation assays were conducted in cultured cells and mouse xenografts. Western blotting analysis of related signal pathways was performed to investigate the molecular mechanisms of the inhibitory effect of DHA and the combination. Other compounds, which inhibit signal transducer and activator of transcription 3 (STAT3), Src-family kinases (SFKs), sphingosine kinase 1 (SPHK1), or the receptor tyrosine kinase (RTK) AXL were also combined with osimertinib in vitro. Results: Osimertinib exerted synergistic cytotoxicity toward FaDu and CAL27 HNSCC cells when combined with DHA. DHA reversed the osimertinib-induced STAT3 and Src, phosphorylation. The double combination inhibited AXL expression. The anticancer potential of osimertinib plus DHA combination was validated in vivo on FaDu and CAL27 xenografts in mice without notable side effects. Conclusions: The results illustrate that the combinatory therapy of osimertinib and DHA, as a repurposing anticancer drug, could be a novel therapeutic strategy for recurrent and/or metastatic HNSCC patients. The findings indicate that a clinical trial is warranted to confirm the benefit of the combination.

scholarly journals Synthetic Evaluation of MicroRNA-1-3p Expression in Head and Neck Squamous Cell Carcinoma Based on Microarray Chips and MicroRNA Sequencing

2021 ◽  
Vol 2021 ◽  
pp. 1-24
Author(s):  
Yubing Chen ◽  
Mingjiang Liu ◽  
Hu Jin ◽  
Bo Peng ◽  
Luo Dai ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Gene Expression Omnibus ◽  
Neck Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Regulatory Pathways

Background. MicroRNA-1-3p (miR-1-3p) exerts significant regulation in various tumor cells, but its molecular mechanisms in head and neck squamous cell carcinoma (HNSCC) are still ill defined. This study is aimed at detecting the expression of miR-1-3p in HNSCC and at determining its significant regulatory pathways. Methods. Data were obtained from the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Oncomine, ArrayExpress, Sequence Read Archive (SRA) databases, and additional literature. Expression values of miR-1-3p in HNSCC were analyzed comprehensively. The R language software was employed to screen differentially expressed genes, and bioinformatics assessment was performed. One sequence dataset (HNSCC: n = 484 ; noncancer: n = 44 ) and 18 chip datasets (HNSCC: n = 656 ; noncancer: n = 199 ) were obtained. Results. The expression of miR-1-3p in HNSCC was visibly decreased in compare with noncancerous tissues. There were distinct differences in tumor state ( P = 0.0417 ), pathological stage ( P = 0.0058 ), and T stage ( P = 0.0044 ). Comprehensive analysis of sequence and chip data also indicated that miR-1-3p was lowly expressed in HNSCC. The diagnostic performance of miR-1-3p in HNSCC is reflected in the sensitivity and specificity of the collection, etc. Bioinformatics analysis showed the possible biological process, cellular component, molecular function, and KEGG pathways of miR-1-3p in HNSCC. And ITGB4 was a possible target of miR-1-3p.Conclusions. miR-1-3p’s low expression may facilitate tumorigenesis and evolution in HNSCC through signaling pathways. ITGB4 may be a key gene in targeting pathways but still needs verification through in vitro experiments.

scholarly journals Single-Cell Spatial Proteomics Analyses of Head and Neck Squamous Cell Carcinoma Reveal Tumor Heterogeneity and Immune Architectures Associated with Clinical Outcome

2021 ◽  
Author(s):  
Katie E. Blise ◽  
Shamilene Sivagnanam ◽  
Grace L. Banik ◽  
Lisa M. Coussens ◽  
Jeremy Goecks
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Single Cell ◽  
Squamous Cell ◽  
Immune Cells ◽  
Spatial Organization ◽  
Patient Survival ◽  
Response To Therapy ◽  
Neck Squamous Cell Carcinoma

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.

scholarly journals Levels of TGF-α and EGFR Protein in Head and Neck Squamous Cell Carcinoma and Patient Survival

1998 ◽  
Vol 90 (11) ◽  
pp. 824-832 ◽  
Author(s):  
Jennifer Rubin Grandis ◽  
Mona F. Melhem ◽  
William E. Gooding ◽  
Roger Day ◽  
Valerie A. Holst ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Patient Survival ◽  
Neck Squamous Cell Carcinoma

scholarly journals Bioinformatic Analysis of Transcriptome Changes Underlying Metformin-induced Reversal of Drug Resistance in Head and Neck Squamous Cell Carcinoma Cells

2021 ◽  
Author(s):  
shanchun hou ◽  
Qi Li ◽  
Wulong Jin ◽  
You Peng ◽  
Sujuan Niu ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Transcriptome Analysis ◽  
Molecular Mechanisms ◽  
Carcinoma Cells ◽  
Neck Squamous Cell Carcinoma ◽  
Repair Capacity

Abstract Background: Metformin is the first-line drug for type II diabetes, and recent studies indicate that metformin plays an inhibitory role in multiple cancers. Metformin can also enhance the effect of chemotherapy. Although head and neck squamous cell carcinoma cells are sensitive to metformin, the mechanisms related to the metformin response and the chemosensitization effect have not been fully studied. Results: In this study, we aimed to elucidate the molecular mechanisms of metformin in HNSCC by transcriptome analysis and to reveal the underlying mechanisms of the sensitizing effects of metformin by combined online dataset analysis. mRNA sequencing and functional analysis of HNSCC samples after metformin treatment and functional analysis of mRNAs with opposite metformin-induced effects in chemosensitive versus chemoresistant cells revealed the molecular pathways, mainly the base excision repair pathway, by which this small molecule drug sensitizes HNSCC cells to treatment. Conclusions: These findings indicate that metformin exerts a hypersensitization effect by regulating the BER pathway in tumour cells, reducing their self-repair capacity after chemotherapy-induced DNA damage. In addition, the genes identified by transcriptome analysis are candidates for further investigation into the effector targets of metformin in the inhibition of HNSCC and could be applied to improve the treatment in HNSCC patients who develop resistance after advanced chemotherapy.

scholarly journals MAP2K1 is a potential therapeutic target in erlotinib resistant head and neck squamous cell carcinoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ankit P. Jain ◽  
Krishna Patel ◽  
Sneha Pinto ◽  
Aneesha Radhakrishnan ◽  
Vishalakshi Nanjappa ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Mapk Pathway ◽  
Acquired Resistance ◽  
Unmet Need ◽  
Neck Squamous Cell Carcinoma ◽  
Integrated Analysis

AbstractEpidermal growth factor receptor (EGFR) targeted therapies have shown limited efficacy in head and neck squamous cell carcinoma (HNSCC) patients despite its overexpression. Identifying molecular mechanisms associated with acquired resistance to EGFR-TKIs such as erlotinib remains an unmet need and a therapeutic challenge. In this study, we employed an integrated multi-omics approach to delineate mechanisms associated with acquired resistance to erlotinib by carrying out whole exome sequencing, quantitative proteomic and phosphoproteomic profiling. We observed amplification of several genes including AXL kinase and transcription factor YAP1 resulting in protein overexpression. We also observed expression of constitutively active mutant MAP2K1 (p.K57E) in erlotinib resistant SCC-R cells. An integrated analysis of genomic, proteomic and phosphoproteomic data revealed alterations in MAPK pathway and its downstream targets in SCC-R cells. We demonstrate that erlotinib-resistant cells are sensitive to MAPK pathway inhibition. This study revealed multiple genetic, proteomic and phosphoproteomic alterations associated with erlotinib resistant SCC-R cells. Our data indicates that therapeutic targeting of MAPK pathway is an effective strategy for treating erlotinib-resistant HNSCC tumors.

scholarly journals The Landscape of Transmembrane Protein Family Members in Head and Neck Cancers: Their Biological Role and Diagnostic Utility

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4737
Author(s):  
Oliwia Koteluk ◽  
Antonina Bielicka ◽  
Żaneta Lemańska ◽  
Kacper Jóźwiak ◽  
Weronika Klawiter ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cell ◽  
Patient Survival ◽  
Gene Set Enrichment Analysis ◽  
Neck Squamous Cell Carcinoma ◽  
Expression Levels

Background: Transmembrane proteins (TMEM) constitute a large family of proteins spanning the entirety of the lipid bilayer. However, there is still a lack of knowledge about their function or mechanism of action. In this study, we analyzed the expression of selected TMEM genes in patients with head and neck squamous cell carcinoma (HNSCC) to learn their role in tumor formation and metastasis. Materials and Methods: Using TCGA data, we analyzed the expression levels of different TMEMs in both normal and tumor samples and compared those two groups depending on clinical-pathological parameters. We selected four TMEMs whose expression was highly correlated with patient survival status and subjected them to further analysis. The pathway analysis using REACTOME and the gene set enrichment analysis (GSEA) were performed to evaluate the association of those TMEMs with genes involved in hallmarks of cancer as well as in oncogenic and immune-related pathways. In addition, the fractions of different immune cell subpopulations depending on TMEM expression were estimated in analyzed patients. The results for selected TMEMs were validated using GEO data. All analyses were performed using the R package, Statistica, and Graphpad Prism. Results: We demonstrated that 73% of the analyzed TMEMs were dysregulated in HNSCC and depended on tumor localization, smoking, alcohol consumption, or HPV infection. The expression levels of ANO1, TMEM156, TMEM173, and TMEM213 correlated with patient survival. The four TMEMs were also upregulated in HPV-positive patients. The elevated expression of those TMEMs correlated with the enrichment of genes involved in cancer-related processes, including immune response. Specifically, overexpression of TMEM156 and TMEM173 was associated with immune cell mobilization and better survival rates, while the elevated ANO1 expression was linked with metastasis formation and worse survival. Conclusions: In this work, we performed a panel of in silico analyses to discover the role of TMEMs in head and neck squamous cell carcinoma. We found that ANO1, TMEM156, TMEM173, and TMEM213 correlated with clinical status and immune responses in HNSCC patients, pointing them as biomarkers for a better prognosis and treatment. This is the first study describing such the role of TMEMs in HNSCC. Future clinical trials should confirm the potential of those genes as targets for personalized therapy of HNSCC.

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