1999 Media Guide

1999 Men\u27s Track and Field Media Guide, George Fox College

Meta-pathway activity identified in 44 HNSCC and 25 UPPP samples.

<p>Relative activity of meta-pathways associated with (a) UPPP, (b) HNSCC, (c) HPV-positive, and (d) HPV-negative samples.</p

GLI1 and CTNNB1 expression in TCGA.

<p>Boxplots of (a) GLI1 and (b) CTNNB1 expression in TCGA RNA-seq data.</p

Preferential Activation of the Hedgehog Pathway by Epigenetic Modulations in HPV Negative HNSCC Identified with Meta-Pathway Analysis

<div><p>Head and neck squamous cell carcinoma (HNSCC) is largely divided into two groups based on their etiology, human papillomavirus (HPV)-positive and –negative. Global DNA methylation changes are known to drive oncogene and tumor suppressor expression in primary HNSCC of both types. However, significant heterogeneity in DNA methylation within the groups results in different transcriptional profiles and clinical outcomes. We applied a meta-pathway analysis to link gene expression changes to DNA methylation in distinguishing HNSCC subtypes. This approach isolated specific epigenetic changes controlling expression in HPV− HNSCC that distinguish it from HPV+ HNSCC. Analysis of genes identified Hedgehog pathway activation specific to HPV− HNSCC. We confirmed that <i>GLI1</i>, the primary Hedgehog target, showed higher expression in tumors compared to normal samples with HPV− tumors having the highest <i>GLI1</i> expression, suggesting that increased expression of <i>GLI1</i> is a potential driver in HPV− HNSCC. Our algorithm for integration of DNA methylation and gene expression can infer biologically significant molecular pathways that may be exploited as therapeutics targets. Our results suggest that therapeutics targeting the Hedgehog pathway may be of benefit in HPV− HNSCC. Similar integrative analysis of high-throughput coupled DNA methylation and expression datasets may yield novel insights into deregulated pathways in other cancers.</p></div

GLI1 expression in the validation cohort.

<p>(a) GLI1 expression in validation cohort measured with RT-PCR. values are computed relative to the mean count of for normal samples.</p

Clustering combined DNA methylation and gene expression data from 44 HNSCC samples and 25 UPPP samples.

<p>Patterns identified with hierarchical clustering for sample-by-sample Pearson correlations for combined gene expression and log transformed DNA methylation data, colored by whether samples are normal (black, labeled “N”), HPV-positive (blue, labeled “+”) and HPV-negative (red, labeled “−”) samples.</p

Pathway enrichment Summary of the pathways that were significantly enriched (p<0.05) in each meta-pathway associated with HNSCC.

<p>Pathway enrichment Summary of the pathways that were significantly enriched (p<0.05) in each meta-pathway associated with HNSCC.</p

Clinical attributes of samples Summary of clinical features of samples in discovery, validation, and TCGA sample cohorts.

<p>Clinical attributes of samples Summary of clinical features of samples in discovery, validation, and TCGA sample cohorts.</p

Discovery tumor clinical characteristics.

<p>Discovery tumor clinical characteristics.</p

Validation tumor clinical characteristics.

<p>Validation tumor clinical characteristics.</p