A Novel Orthotopic Mouse Model of Head and Neck Cancer and Lymph Node Metastasis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE41893 | GEO | 2012/10/29
SECONDARY ACCESSION(S): PRJNA178413
REPOSITORIES: GEO
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Project description:Analysis of the genes involved in the metastasis of head and neck squamous cell carcinoma (HNSCC). We hypothesized that there would be overexpression of certain genes in the highly metastatic USC-HN1-GFP-G1 and USC-HN1-GFP-G2 cell lines compared to the parental USC-HN1-GFP cell line. We used the USC-HN1 cell line stably transfected with H2B-GFP and developed an immortal cell line (USC-HN1-GFP), which was injected into the tongues of SCID/nude mice. The metastatic cells were collected at the LN, separated and cultured, forming an immortal USC-HN1-GFP-G1 cell line. These cells were reinjected into the tongues of mice and the USC-HN1-GFP-G2 cell line was formed by the same LN collection method. The gene expression in these three cell lines were compared using Illumina microarray chips.
2012-10-29 | E-GEOD-41893 | biostudies-arrayexpress
Project description:A classifier was build on 82 training samples to differentiate between lymph node negative (N0) and lymph node metastasis (N+) head and neck squamous-cell carcinomas (HNSCC). The 102 predictor genes that resulted from this classifier where then validated against a independent validation set.
2005-01-09 | E-UMCU-11 | biostudies-arrayexpress
Project description:Prognosis of head and neck squamous cell carcinoma (HNSCC) is largely determined by the extent of lymph node (LN) metastasis at diagnosis, and this appears to be controlled by cancer cell genetics. To examine the role of these genes in LN metastasis, we created a human-in-mouse orthotopic model of HNSCC and performed comparative microarray analysis of gene expression between populations of HNSCC cell lines derived before and after serial transplantation and in vivo metastasis in mice. Microarray analysis comparing the USC-HN3-GFP, USC-HN3-GFP-G1 and USC-HN3-GFP-G2 cell lines identified overexpression of genes implicated in epithelial-to- mesenchymal transition and the formation of cancer stem cells, including CAV-1, TLR-4 (Toll-like receptor 4), MMP-7 (matrix metalloproteinase 7), ALDH1A3, OCT-4 and TRIM-29. Ingenuity Pathway Analysis confirmed upregulation of respective gene signaling pathways in the USC-HN1-GFP-G2 cell line. Patient HNSCC samples from advanced stages overexpressed ALDH1A3, CAV-1 and MMP-7. Our results show that CAV-1, TLR-4, MMP-7, ALDH1A3, OCT-4 and TRIM-29 have increased expression in HNSCC cells selected for an enhanced metastatic phenotype and suggest that these genes may have an important role in the metastatic potential of HNSCC cells. Inhibition of these genes may therefore have prognostic and therapeutic utility in HNSCC.
| S-EPMC3816223 | biostudies-literature
Project description:A growing proportion of head and neck squamous cell carcinomas (HNSCC) is associated with the human papilloma virus (HPV), particularly HPV16. We compare tumors with different HPV16 DNA and RNA (E6*I) status from 290 consecutively recruited HNSCC patients by gene expression profiling and targeted sequencing of 50 genes. We confirm that the HPV16 DNA+ RNA+ tumors are molecularly distinct from the HPV-negative (DNA-) HNSCC and have elevated expression of cell cycle genes and rare TP53 mutations (3.6%, 1/28). We show that tumors with non-transcriptionally active HPV16 (DNA+ RNA-) are similar to HPV DNA- tumors regarding gene expression and frequency of TP53 mutations (47%, 8/17 and 43%, 72/167, respectively). Furthermore, we identify four gene expression clusters. They moderately but significantly differ in overall survival. One cluster exhibits high expression of immune response genes (IR) and contains most of the HPV16 DNA+ RNA+ patients. The IR cluster and disruptive TP53 mutations are associated with lymph node metastasis independent of HPV16 status and we validate each of these associations in another large data set. Consistent with earlier studies, disruptive TP53 mutations are prognostically unfavorable. Our findings underscore the importance of measuring the HPV16 RNA (E6*I) and TP53-mutation status for patient stratification and for the first time identify associations of an immune response-related gene expression cluster and TP53 mutations with lymph node metastasis in HNSCC. A total of 300 samples were considered. Quality control procedures were applied to microarray probe-level intensity files. A total of 270 tumor arrays remained after removing low-quality arrays, duplicate arrays, and arrays from non-HNSCC samples. Expression values were log2-transformed and normalized using RSN.
2015-06-24 | E-GEOD-65858 | biostudies-arrayexpress
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:This study represents a proteomic resource for HNSCC and SQCLC with quantitative protein expression data for 7800 proteins and provides a proteomic diagnostic signature for classification for undetermined secondary lung tumors in HNSCC patients. By quantitative mass-spectrometry-based proteomics, we characterized a cohort of 63 squamous cell carcinomas of the lung (SQCLC), 49 of the head and neck region (HNSCC) and 51 HNSCC-correlated lung tumors with squamous cell histology that evolved in the course of the disease.
2018-08-06 | PXD007705 | Pride
Project description:A growing proportion of head and neck squamous cell carcinomas (HNSCC) is associated with the human papilloma virus (HPV), particularly HPV16. We compare tumors with different HPV16 DNA and RNA (E6*I) status from 290 consecutively recruited HNSCC patients by gene expression profiling and targeted sequencing of 50 genes. We confirm that the HPV16 DNA+ RNA+ tumors are molecularly distinct from the HPV-negative (DNA-) HNSCC and have elevated expression of cell cycle genes and rare TP53 mutations (3.6%, 1/28). We show that tumors with non-transcriptionally active HPV16 (DNA+ RNA-) are similar to HPV DNA- tumors regarding gene expression and frequency of TP53 mutations (47%, 8/17 and 43%, 72/167, respectively). Furthermore, we identify four gene expression clusters. They moderately but significantly differ in overall survival. One cluster exhibits high expression of immune response genes (IR) and contains most of the HPV16 DNA+ RNA+ patients. The IR cluster and disruptive TP53 mutations are associated with lymph node metastasis independent of HPV16 status and we validate each of these associations in another large data set. Consistent with earlier studies, disruptive TP53 mutations are prognostically unfavorable. Our findings underscore the importance of measuring the HPV16 RNA (E6*I) and TP53-mutation status for patient stratification and for the first time identify associations of an immune response-related gene expression cluster and TP53 mutations with lymph node metastasis in HNSCC.
2015-06-24 | GSE65858 | GEO
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
2009-03-11 | E-GEOD-12020 | biostudies-arrayexpress
Project description:To investigate the mechanism of cetuximab resistance in head and neck squamous cell carcinoma (HNSCC), we performed single-cell RNA sequencing analysis in biopsy from two HNSCC patients before and after cetuximab treatment.
2022-04-01 | GSE173647 | GEO
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