Primary head and neck squamous cell carcinoma keratinocyte RNA expression in culture.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE277508 | GEO | 2025/06/11
REPOSITORIES: GEO
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Project description:Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers in India. Despite improvements in treatment strategy, the survival rates of HNSCC patients remains poor. Thus, it is necessary to identify biomarkers that can be used for early detection of disease. In this study, we employed iTRAQ-based quantitative mass spectrometry analysis to identify dysregulated proteins from a panel of head and neck squamous cell carcinoma (HNSCC) cell lines. We identified 2,468 proteins, of which 496 proteins were found to be dysregulated in at least two HNSCC cell lines compared to immortalized normal oral keratinocytes. We detected increased expression of replication protein A1 (RPA1) and heat shock protein family H (Hsp110) member 1 (HSPH1), in HNSCC cell lines compared to control. The differentially expressed proteins were further validated using parallel reaction monitoring (PRM) and western blot analysis in HNSCC cell lines. Immunohistochemistry-based validation using HNSCC tissue microarrays revealed overexpression of RPA1 and HSPH1 in 15.7% and 32.2% of the tested cases, respectively. Our study illustrates quantitative proteomics as a robust approach for identification of potential HNSCC biomarkers.
2018-09-19 | PXD009241 | Pride
Project description:60 fresh frozen HNSCC from the University of North Carolina at Chapel Hill (UNC) were obtained from the UNC Tissue Procurement Facility under an IRB approved protocol. 55 tumor samples were collected from the primary tumor and five tumor samples were collected from a local recurrence at the primary site; one tumor also had a sample of the primary tumor and an associated lymph node metastasis . In addition, we profiled three normal tonsillar epithelium samples that were collected from three pediatric patients following routine tonsillectomy and four HNSCC tumor derived cell lines (UNC7, UMSCCA1, CAL27 and JHU022). Each experimental sample (tumor, normal or cell line) was assayed versus a â??common referenceâ?? sample that was a pool of total RNA derived from 30 of the HNSCC samples. This tumor pool reference strategy has been successfully used in another profiling study. In total, 78 experiments were performed, which utilized three separate preparations of the common reference pool. Keywords = Head and neck cancer Keywords = gene expression profiles Keywords = microarray
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Project description:60 fresh frozen HNSCC from the University of North Carolina at Chapel Hill (UNC) were obtained from the UNC Tissue Procurement Facility under an IRB approved protocol. 55 tumor samples were collected from the primary tumor and five tumor samples were collected from a local recurrence at the primary site; one tumor also had a sample of the primary tumor and an associated lymph node metastasis . In addition, we profiled three normal tonsillar epithelium samples that were collected from three pediatric patients following routine tonsillectomy and four HNSCC tumor derived cell lines (UNC7, UMSCCA1, CAL27 and JHU022). Each experimental sample (tumor, normal or cell line) was assayed versus a “common reference” sample that was a pool of total RNA derived from 30 of the HNSCC samples. This tumor pool reference strategy has been successfully used in another profiling study. In total, 78 experiments were performed, which utilized three separate preparations of the common reference pool. Keywords = Head and neck cancer Keywords = gene expression profiles Keywords = microarray Keywords: parallel sample
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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
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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.
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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.
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Project description:This SuperSeries is composed of the following subset Series: GSE11929: Identification of a subgroup of head and neck cancers lacking numerical chromosomal aberrations GSE11931: Copy Number Alterations in HNSCC with or without Oncogene Expressing Human Papillomavirus Refer to individual Series
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Project description:We characterized n=134 HNSCC by Quantseq 3´-RNA-sequencing for their transcriptional profiles in order to analyze differential expression of clinically relevant subgroups, define transcriptionally defined molecular subgroups and to characterize the tumor microenvironment by gene expression devonvolution approaches.
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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.
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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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