P63 Directs Subtype Specific Gene Expression in HPV+ Head and Neck Squamous Cell Carcinoma
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PROVIDER: PRJNA754760 | ENA |
REPOSITORIES: ENA
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Project description:Gene expression analysis of p63 knockdown in 2 HPV+ HNSCC cell lines using RNA-seq, Genomic profiling of p63 binding across 2 HPV+ HNSCC cell lines, Epigenomic landscape of 2 HPV+ HNSCC cell lines
2022-04-19 | GSE182133 | GEO
Project description:We report single cell transcriptome data from HPV-positive head and neck squamous cell carcinoma patients
2023-06-20 | GSE173468 | GEO
Project description:Introduction: Human Papilloma Virus (HPV) is associated with a subset of head and neck squamous cell carcinoma (HNSCC), between 15% and 35% of HNSCC harboring HPV, almost exclusively of subtype 16. Demographic and exposure differences between HPV-positive (+) and negative (-) HNSCCs suggest that HPV(+) tumors may constitute a subclass with different biology, while clinical differences have also been observed. In this study, gene expression profiles of HPV(+) and (-) tumors were compared to further explore the biological effect of HPV in HNSCC. Methods: Thirty-six HNSCC tumors were analyzed for gene expression using Affymetrix Human 133U Plus 2.0 GeneChip and for HPV using consensus primers for HPV L1, E6 and E7 by PCR and RT-PCR. Results: Eight (22%) of 36 tumors were positive for HPV, all of the HPV 16 subtype, and the HPV positive samples also expressed viral HPV E6 mRNA determined by RT-PCR. Patients with HPV(+) HNSCCs were on average younger than those with HPV(-) tumors (mean age 50.2 vs. 58.7). Statistical analysis using Significance Analysis of Microarrays (SAM) based on HPV status as a supervising parameter resulted in a list of 91 genes that were differentially expressed with statistical significance. Results for a sub-set of these genes were verified by RT-PCR. Genes highly expressed in HPV(+) samples included cell cycle regulators (p16INK4A, p18 and CDK2) and transcription factors (TAF7L, RFC4, RPA2 and TFDP2). The microarray data were also investigated using DIGMap to map genes by chromosomal location. A large number of genes on chromosome 3q24-qter was found to be overrepresented in HPV(+) tumors. Conclusion: The gene expression profile associated with HPV reflects alterations in cell cycle and proliferation signals. Further investigation of differentially expressed genes may reveal the unique pathways in HPV(+) tumors that may explain the different natural history and biological properties of these tumors. These properties may be exploited as a target of novel therapeutic agents in HNSCC treatment. Keywords: HPV, HNSCC, head and neck cancer, human, human papilloma virus
2005-11-28 | GSE3292 | GEO
Project description:Purpose: There is substantial heterogeneity within the human papillomavirus (HPV) positive head and neck cancer (HNC) tumors that predispose them to different outcomes, however this subgroup is poorly characterized due to various historical reasons. Experimental Design: we perform unsupervised gene expression clustering on well-annotated HPV(+) HNC samples from two cohorts ( 84 total primary tumors), as well as 18 HPV(-) HNCs, to discover subtypes, and begin to characterize the differences between the subtypes in terms of their HPV characteristics, pathway activity, whole-genome somatic copy number variations and mutation frequencies. Results: We identified two distinctive HPV(+) subtypes by unsupervised clustering. Membership in the HPV(+) subtypes correlates with genic viral integration status, E2/E4/E5 expression levels and the ratio of spliced to full length HPV oncogene E6. The subtypes also show differences in copy number alterations, in particular the loss of chr16q and gain of chr3q, PIK3CA mutation, and in the expression of genes involved in several biological processes related to cancer, including immune response, oxidation-reduction process, and keratinocyte and mesenchymal differentiation. Conclusion: Our characterization of two subtypes of HPV(+) tumors provides valuable molecular level information in relation to the alternative paths to tumor development and to that of HPV(-) HNCs. Together, these results will shed light on stratifications of the HPV(+) HNCs and will help to guide personalized care for HPV(+) HNC patients. 36 head and neck primary tumors (18 HPV+ and 18 HPV-) and their matched blood samples were collected and genotyped by Illumina OmniExpress SNP array. RNA-seq was also performed on the same set of tumor samples.
2016-05-13 | E-GEOD-74927 | biostudies-arrayexpress
Project description:Human papillomaviruses (HPVs) are associated with nearly all cervical cancers (CCs), 20-30% of head and neck cancers (HNCs), and other cancers. Because HNCs also arise in HPV-negative patients, this type of cancer provides unique opportunities to define similarities and differences of HPV-positive versus HPV-negative cancers arising in the same tissue. Here, we describe genome-wide expression profiling of 84 HNCs, CCs and site-matched normal epithelial samples in which we used laser capture microdissection to enrich samples for tumor-derived versus normal epithelial cells. This analysis revealed that HPV+HNCs and CCs differed in their patterns of gene expression yet shared many changes compared to HPV-HNCs. Some of these shared changes were predicted, but many others were not. Notably, HPV+HNCs and CCs were found to be upregulated in their expression of a distinct and larger subset of cell cycle genes than observed in HPV-HNC. Moreover, HPV+ cancers over-expressed testis-specific genes that are normally expressed only in meiotic cells. Many, though not all, of the hallmark differences between HPV+HNC and HPV-HNC were a direct consequence of HPV and in particular the viral E6 and E7 oncogenes. This included a novel association of HPV oncogenes with testes specific gene expression. These findings in primary human tumors provide novel biomarkers for early detection of HPV+ and HPV- cancers, and emphasize the potential value of targeting E6 and E7 function, alone or combined with radiation and/or traditional chemotherapy, in the treatment of HPV+ cancers. Keywords: Gene expression ptofiles of primary cancers
2007-05-15 | GSE6791 | GEO
Project description:Two HPV(+) head and neck cancer cell lines (UPCI-SCC-090, UM-SCC-104), one HPV(–) head and neck cancer cell line (FaDu) and one nasopharyngeal epithelial cell line (NP69SV40T) were subjected to RNA-seq analysis.
2023-01-06 | GSE211322 | GEO
Project description:Purpose: Human papilloma virus (HPV) associated head and neck squamous cell carcinoma (HNSCC) has a better prognosis than HPV(-) negative cancer. This may be due, in part, to the higher number of tumour infiltrating lymphocytes (TIL) in HPV(+) tumours. We used RNAseq to evaluate whether these differences in clinical behaviour could be explained simply by a numerical difference in TILs or whether there was a fundamental difference between TILs in these two settings. Patients and methods: Twenty-three consecutive HNSCC cases with high and moderate TIL density were subjected to RNAseq analysis. Differentially expressed genes (DEG) between 10 HPV(+) and 13 HPV(-) tumours were identified with EdgeR. Immune subset analysis was performed using, FAIME (Functional Analysis of Individual Microarray Expression) and Immune gene transcript count analysis. Results: 1634 genes were differentially expressed. There was a dominant immune signature in HPV(+) tumours. After normalizing expression profiles for numerical differences in T cells and B cells, 437 significantly DEGs still remained. A B-cell associated signature emerged, which segregated HPV(+) from HPV(-) cancers and included CD200, STAG3, GGA2, SPIB and ADAM28. Differential expression of these genes was confirmed by real-time quantitative PCR and immunohistochemistry. Conclusion: In our dataset, the difference associated with T-cells between patients with HPV(+) and (-) HNSCC was predominantly numerical. However, when TIL numbers are corrected, a distinct differential B-cell signature was revealed. mRNA profiles of 10 HPV driven (HPV+) and 13 HPV independant (HPV-) head and neck squamous cell carcinoma (HNSCC) tumours were generated by RNA-Seq, using Illumina HiSeq 2000.
2016-09-01 | E-GEOD-72536 | biostudies-arrayexpress
Project description:Head and neck squamous cell carcinomas (HNSCC) driven by human papillomavirus (HPV) generally have a more favourable prognosis. We hypothesized that HPV-positive HNSCC may be identified based on a miRNA signature according to their specific molecular pathogenesis and are characterized by a unique transcriptome compared to HPV-negative HNSCC. We characterized the miRNA-expression patterns of the tumors from 229 head and neck squamous cell carcinoma patients by Agilent miRNA microarrays in order to define a HPV-predicting miRNA signature.
2023-05-10 | GSE175509 | GEO
Project description:Background: Human papillomavirus has been shown to have a causal role in the development of head and neck squamous cell carcinoma and represents a distinct and well-defined pathology. While HPV-positive HNSCC is associated with a better response to treatment and prognosis, a subset of patients do not respond favorably to current standard of care thus suffering unnecessary morbidity and delay to receive effective therapy. Methods: RNA from nineteen patients with HPV-positive HNSCC was subjected to gene expression analysis using Affymetrix microarrays. HPV-status was confirmed by detection of HPV16 E7 with RT-PCR. Results: In addition to specific genetic biomarkers (including LCE3D, KRTDAP, HMOX1, KRT19, MDK, TSPAN1), differentially expressed genes were highly represented in the cell processes of genomic stability, cell cycle, and DNA damage. Conclusions: This pilot study suggests possible biomarkers that predict response to chemoradiation therapy. These data can potentially lead to an assay that can be used clinically to predict HPV-positive HNSCC patients that will not benefit from chemoradiation, thus helping clinicians to lower morbidity and get selected patients to surgery faster. HPV-positive head and neck squamous cell carcinoma (HNSCC) has a good prognosis with a large percentage of patients responding to therapy. However, a certain percentage of patients do not respond. Gene expression data from Affymetrix Human Exon 1.0ST microarrays was utilized to compare patients that responded to therapy with those that did not respond.
2014-12-19 | E-GEOD-40020 | biostudies-arrayexpress
Project description:Background. Head and neck squamous cell carcinomas (HNSCCs) represent a heterogeneous group of cancers, for which human papilloma virus (HPV) infection is an emerging risk factor. Previous studies showed promoter hypermethylation in HPV(+) oropharyngeal cancers, but only few consistent target genes have been so far described and the evidence of a functional impact on gene expression is still limited. Methods. We performed global and stratified pooled analyses of epigenome-wide data in HNSCCs based on the Illumina HumanMethylation450 bead-array data in order to identify tissue-specific components and common viral epigenetic targets in HPV-associated tumours . Results. We identified novel differentially methylated CpGs and regions associated with viral infection that are independent of the anatomic site. In particular, most hypomethylated regions were characterized by a marked loss of CpG island boundaries, which showed significant correlations with expression of neighbouring genes. Moreover, a subset of only 5 CpGs in few hypomethylated regions predicted HPV status with a high level of specificity in different cohorts. Finally, this signature was a better predictor of survival compared with HPV status determined by viral gene expression by RNA-Sequencing in the TCGA cohort. Conclusions. We identified a novel epigenetic signature of HPV infection in HNSCCs which is independent of the anatomic site, is functionally correlated with gene expression and may be leveraged for improved stratification of prognosis in HNSCCs.
2017-02-18 | GSE95036 | GEO