15 research outputs found

    Additional file 3: of Bibliometric trends of health economic evaluation in Sub-Saharan Africa

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    Database of included studies and characteristics, network articles, authorship and collaborations. (XLSX 182 kb

    Expression Microarray Analysis Reveals Alternative Splicing of <i>LAMA3</i> and <i>DST</i> Genes in Head and Neck Squamous Cell Carcinoma

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    <div><p>Purpose</p><p>Prior studies have demonstrated tumor-specific alternative splicing events in various solid tumor types. The role of alternative splicing in the development and progression of head and neck squamous cell carcinoma (HNSCC) is unclear. Our study queried exon-level expression to implicate splice variants in HNSCC tumors.</p><p>Experimental Design</p><p>We performed a comparative genome-wide analysis of 44 HNSCC tumors and 25 uvulopalatopharyngoplasty (UPPP) tissue samples at an exon expression level. In our comparison we ranked genes based upon a novel score—the Maximum-Minimum Exon Score (MMES) – designed to predict the likelihood of an alternative splicing event occurring. We validated predicted alternative splicing events using quantitative RT-PCR on an independent cohort.</p><p>Results</p><p>After MMES scoring of 17,422 genes, the top 900 genes with the highest scores underwent additional manual inspection of expression patterns in a graphical analysis. The genes <i>LAMA3, DST, VEGFC, SDHA, RASIP1</i>, and <i>TP63</i> were selected for further validation studies because of a high frequency of alternative splicing suggested in our graphical analysis, and literature review showing their biological relevance and known splicing patterns. We confirmed <i>TP63</i> as having dominant expression of the short <i>DeltaNp63</i> isoform in HNSCC tumor samples, consistent with prior reports. Two of the six genes (<i>LAMA3</i> and <i>DST</i>) validated by quantitative RT-PCR for tumor-specific alternative splicing events (Student's t test, P<0.001).</p><p>Conclusion</p><p>Alternative splicing events of oncologically relevant proteins occur in HNSCC. The number of genes expressing tumor-specific splice variants needs further elucidation, as does the functional significance of selective isoform expression.</p></div

    Outlier Analysis Defines Zinc Finger Gene Family DNA Methylation in Tumors and Saliva of Head and Neck Cancer Patients

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    <div><p>Head and Neck Squamous Cell Carcinoma (HNSCC) is the fifth most common cancer, annually affecting over half a million people worldwide. Presently, there are no accepted biomarkers for clinical detection and surveillance of HNSCC. In this work, a comprehensive genome-wide analysis of epigenetic alterations in primary HNSCC tumors was employed in conjunction with cancer-specific outlier statistics to define novel biomarker genes which are differentially methylated in HNSCC. The 37 identified biomarker candidates were top-scoring outlier genes with prominent differential methylation in tumors, but with no signal in normal tissues. These putative candidates were validated in independent HNSCC cohorts from our institution and TCGA (The Cancer Genome Atlas). Using the top candidates, <i>ZNF14</i>, <i>ZNF160</i>, and <i>ZNF420</i>, an assay was developed for detection of HNSCC cancer in primary tissue and saliva samples with 100% specificity when compared to normal control samples. Given the high detection specificity, the analysis of ZNF DNA methylation in combination with other DNA methylation biomarkers may be useful in the clinical setting for HNSCC detection and surveillance, particularly in high-risk patients. Several additional candidates identified through this work can be further investigated toward future development of a multi-gene panel of biomarkers for the surveillance and detection of HNSCC.</p></div
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