RNA-Seq analysis of Head and Neck Squamous cell carcinoma cell-lines
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE68872 | GEO | 2017/02/09
SECONDARY ACCESSION(S): PRJNA283957
REPOSITORIES: GEO
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Project description:Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer world wide, and survival rates range from 40-80% depending on subsite. As novel treatment strategies are investigated, comprehensively characterized cell lines representative of the diversity seen in patients will be crucial to correlating genetic and phenotypic features with therapeutic response. The University of Michigan has generated a large panel of HNSCC cell lines that are utilized in laboratories worldwide. Here, we provide transcriptome sequencing of 36 of these cell lines in addition to 5 HNSCC lines derived elsewhere to inform selection of model systems for future studies.
2019-02-26 | GSE126975 | GEO
Project description:To identify the activated tyrosine kinase signaling pathways in HNSCC, we carried out phosphotyrosine profiling using a panel of HNSCC cell lines compared to a normal oral keratinocyte. A total of 61 unique phosphosites were identified across these cell lines. Dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) was one of the kinases hyperphosphorylated at Y321 in all the HNSCC cell lines compared to the normal oral cell line OKF6/TERT1. Inhibition of DYRK1A using its specific siRNA and inhibitor resulted in a decrease in the invasion and colony formation ability of the HNSCC cell lines. Further, the treatment of mice bearing HNSCC xenograft tumors with DYRK1A inhibitor (harmine) showed regression of tumor growth. Our results demonstrate that DYRK1A could be a novel therapeutic target in HNSCC.
2018-10-24 | PXD002132 | Pride
Project description:Aberrant activation of splicing regulators contributes to oncogenic transformation of cells by modulating the alternative splicing events of key oncogenes. Phosphorylation of splicing factors affects subcellular localization and activity of these proteins. Studies have shown a close association between altered phosphorylation of molecules involved in splicing machinery and cancer. We carried out proteomic and phosphoproteomic analysis of head and neck squamous cell carcinoma (HNSCC) cell lines using tandem mass tag (TMT) labeling approach followed by titanium dioxide-based phosphopeptides enrichment method. LC-MS/MS analysis resulted in the identification of 4,920 phosphosites corresponding to 2,288 proteins in six HNSCC cell lines compared to a normal oral cell line; OKF6/TERT1. Among the proteins identified, 23 kinases were found to be hyperphosphorylated in all HNSCC cell lines compared to the normal oral cell line.
2018-10-24 | PXD001862 | Pride
Project description:Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer world wide, and survival rates range from 40-80% depending on subsite. As novel treatment strategies are investigated, comprehensively characterized cell lines representative of the diversity seen in patients will be crucial to correlating genetic and phenotypic features with therapeutic response. The University of Michigan has generated a large panel of HNSCC cell lines that are utilized in laboratories worldwide. Here, we performed Oncoscan array analysis for 33 of these cell lines along with 2 HNSCC lines derived elsewhere to inform selection of model systems for future studies.
2019-02-27 | GSE127231 | GEO
Project description:Gene expression profiles of human HNSCC lines were compared with human normal keratinocytes by 24K cDNA microarray. The ten HNSCC analyzed are derived by the University of Michigan (UM-SCC), representing late stage SCC of different anatomic sites. Principle component analysis and hierarchical gene clustering classified ten cancer cell lines into two subsets, and associated each of the subsets with a distinctive p53 status. Keywords: Gene expression array-based
2008-03-11 | GSE10774 | GEO
Project description:Chromosomal comparative genomic hybridization (CGH) and oligonucleotide microarrays were used to examine 8 HNSCC cell lines and a plot of gene expression levels relative to their position on the chromosome was produced. Three highly up-regulated genes, NT5C3, ANLN and INHBA, were identified on chromosome 7p14. These genes were subjected to quantitative real-time RT-PCR on cDNA and genomic DNA derived from 8 HNSCC cell lines. ANLN and INHBA showed a strong positive correlation between mRNA expression and genomic DNA levels and a similar relationship was shown for the known oncogene, EGFR, at 7p11.2. In clinical samples, ANLN and INHBA showed a significantly higher expression in tumors than in normal tissues. Patients with high expression levels of INHBA had a shorter disease-free survival rate. Therefore, INHBA may be a promising prognostic marker of HNSCC. Keywords: Identification of molecular targets based on genome-wide gene expression profiling
2007-03-01 | GSE7073 | GEO
Project description:The involvement of microRNAs (miRNAs) in cancer and their potential as biomarkers of diagnosis, prognosis and response to therapy is becoming increasingly appreciated. The etiology of head and neck squamous cell carcinoma (HNSCC) is predominantly associated with the synergistic effects of tobacco and alcohol use, as well as Human Papilloma Virus (HPV) infection, which embodies a distinct clinical and biological phenotype. We sought to examine whether the profile of miRNAs in HNSCC varies based on HPV status, and to identify specific miRNAs altered in head and neck carcinogenesis. Total RNA was isolated from 16 HNSCC fresh frozen primary tumors, 5 fresh frozen non-diseased head and neck epithelial tissues, and 2 HNSCC cell lines. The miRNA profile of 662 individual miRNAs in these tissues was examined by microarray. 18 miRNAs are significantly altered in their expression between normal tissues and HNSCC tumors and 5 miRNAs are identified as significantly differentially expressed between HPV-positive (HPV+) and HPV-negative (HPV-) tumors. A striking difference in expression pattern of miRNA was also observed between primary tissues and cell lines. These data suggest that the pattern of miRNA expression may be reflective of disease etiology, and may be useful in the realm of diagnostic biomarkers defining broadly responsive prevention and treatment strategies for HNSCC. These data also suggest that cultured tumor cell lines may be inappropriate for novel miRNA biomarker identification. Keywords: miRNA; Disease-state analysis Expression of 662 individual miRNA was assessed in16 HNSCC fresh frozen primary tumors, 5 fresh frozen non-diseased head and neck epithelial tissues, and 2 HNSCC cell lines were arrayed
2010-05-19 | E-GEOD-11163 | biostudies-arrayexpress
Project description:The bromodomain and extraterminal family members are epigenetic readers and transcriptional coactivators which are critically involved in various biological processes including tumorigenesis. BRD4 has been increasingly appreciated as a key oncogene and promising anticancer target. Here, we sought to characterize the expression of BRD4 and its tumorigenic roles as well as therapeutic targeting in HNSCC. Expression of BRD4 mRNA and protein was determined by bioinformatics interrogation of public available databases, primary HNSCC samples and 4NQO-induced HNSCC animal model. The tumorigenic roles of BRD4 in HNSCC were evaluated by genetic and pharmacological approach in vitro and in vivo. Therapeutic efficiency of BRD4 targeting by JQ1 was assessed in three preclinical models including xenograft model, 4NQO-induced model and patients-derived xenograft model. Gene candidates responsible for therapeutic effects of JQ1 were identified by transcriptional profiling in HNSCC cells after JQ1 exposure. Significant upregulation of BRD4 was found in primary HNSCC samples and 4NQO-induced HNSCC model. Its overexpression associated with aggressive clinicopathological features and inferior overall and disease-free survival. BRD4 depletion by genetic silencing or pharmacological inhibition impaired cell proliferation, migration and invasion and reduced tumor growth and metastasis in vivo. Transcriptional profiling of HNSCC cells following JQ1 exposure identified hundreds of genes which might mediated its antitumor effects and enriched in cancer-relevant pathways. A novel prognostic risk score derived from JQ1-regualted genes was developed to stratify patients into subgroups with favorable or inferior prognosis. Our findings reveal that BRD4 serves as a novel oncogene driving cancer progression and a robust prognostic biomarker in HNSCC. Therapeutic targeting of BRD4 represents a potent and promising strategy against HNSCC.
2019-05-09 | GSE122522 | GEO
Project description:Human cancer cell lines are the most frequently used preclinical models in the study of cancer biology and the development of therapeutics. Although anatomically diverse, human papillomavirus (HPV)-driven cancers have a common etiology and similar mutations that overlap with but are distinct from those found in HPV-negative cancers. Building on prior studies that have characterized subsets of head and neck squamous cell carcinoma (HNSCC) and cervical squamous cell carcinoma (CESC) cell lines separately, we performed genomic, viral gene expression, and viral integration analyses on 74 cell lines that include all readily-available HPV-positive (9 HNSCC, 8 CESC) and CESC (8 HPV-positive, 2 HPV-negative) cell lines and 55 HPV-negative HNSCC cell lines. We used over 700 human tumors for comparison. Mutation patterns in the cell lines were similar to those of human tumors. We confirmed HPV viral protein and mRNA expression in the HPV-positive cell lines. We found HPV types in three CESC cell lines that are distinct from those previously reported. We found that cell lines and tumors had similar patterns of viral gene expression; there were few sites of recurrent HPV integration. As seen in tumors, HPV integration did appear to alter host gene expression in cell lines. The HPV-positive cell lines had higher levels of p16 and lower levels of Rb protein expression than did the HPV-negative lines. Although the number of HPV-positive cell lines is limited, our results suggest that these cell lines represent suitable models for studying HNSCC and CESC, both of which are common and lethal.
2018-11-15 | GSE122512 | GEO
Project description:Highly coordinated, deregulated expressions of microRNAs (miRNA) have been implicated in the development of various cancers, including head and neck squamous cell carcinoma (HNSCC). Outside of HPV infection, molecular classification of HNSCC is lacking, and patient stratification by anatomical location and stage does not account for the heterogenous clinical courses seen. Previous studies have proposed molecular classifications based on gene expression, but none describe the role of microRNA expression in HNSCC subtyping. In this study, we identified reliable miRNA clusters that can be used to subclassify HNSCC tumors as well as other squamous tumors of other anatomic locations. An institutional discovery cohort was generated using miRNA expression data from microarrays, and this was validated using publicly available next-generation microRNA sequencing data from TCGA. Further analysis of these subtypes revealed distinct biological and clinical features of HNSCC tumors based on the miRNA expression profiles, which provides new insights into the pathogenesis and treatment of HNSCC.
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