title: Gene and miRNA expression changes in squamous cell carcinoma of larynx and hypopharynx.
abstract: Laryngo-pharyngeal squamous cell carcinomas are one of the most common head and neck cancers. Despite the presence of a large body of information, molecular biomarkers are not currently used in the diagnosis, treatment and management of patients for this group of cancer. Here, we have profiled expression of genes and microRNAs of larynx and hypopharynx tumors using high-throughput sequencing experiments. We found that matrix metalloproteinases along with SCEL, CRNN, KRT4, SPINK5, and TGM3 among others have significantly altered expression in these tumors. Alongside gene expression, the microRNAs hsa-miR-139, hsa-miR-203 and the hsa-miR-424/503 cluster have aberrant expression in these cancers. Using target genes for these microRNAs, we found the involvement of pathways linked to cell cycle, p53 signaling, and viral carcinogenesis significant (P-values 10(-13), 10(-9) and 10(-7) respectively). Finally, using an ensemble machine-learning tool, we discovered a unique 8-gene signature for this group of cancers that differentiates the group from the other tumor subsites of head and neck region. We investigated the role of promoter methylation in one of these genes, WIF1, and found no correlation between DNA methylation and down-regulation of WIF1. We validated our findings of gene expression, 8-gene signature and promoter methylation using q-PCR, data from TCGA and q-MSP respectively. Data presented in this manuscript has been submitted to the NCBI Geo database with the accession number GSE67994.
authors.affiliation: Ganit Labs, Bio-IT Centre, Institute of Bioinformatics and Applied Biotechnology, Biotech Park, Electronic City, Bangalore, India.
authors.forename: Jayalakshmi
authors.initials: J
authors.lastname: Nair
authors.affiliation: Ganit Labs, Bio-IT Centre, Institute of Bioinformatics and Applied Biotechnology, Biotech Park, Electronic City, Bangalore, India.
authors.forename: Prachi
authors.initials: P
authors.lastname: Jain
authors.affiliation: Ganit Labs, Bio-IT Centre, Institute of Bioinformatics and Applied Biotechnology, Biotech Park, Electronic City, Bangalore, India.
authors.forename: Udita
authors.initials: U
authors.lastname: Chandola
authors.affiliation: Ganit Labs, Bio-IT Centre, Institute of Bioinformatics and Applied Biotechnology, Biotech Park, Electronic City, Bangalore, India.
authors.forename: Vinayak
authors.initials: V
authors.lastname: Palve
authors.affiliation: Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Centre, Narayana Hrudayalaya, Bangalore, India.
authors.forename: N R Harsha
authors.initials: NR
authors.lastname: Vardhan
authors.affiliation: Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Centre, Narayana Hrudayalaya, Bangalore, India.
authors.forename: Ram Bhupal
authors.initials: RB
authors.lastname: Reddy
authors.affiliation: Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Centre, Narayana Hrudayalaya, Bangalore, India.
authors.forename: Vikram D
authors.initials: VD
authors.lastname: Kekatpure
authors.affiliation: Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Centre, Narayana Hrudayalaya, Bangalore, India.
authors.forename: Amritha
authors.initials: A
authors.lastname: Suresh
authors.affiliation: Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Centre, Narayana Hrudayalaya, Bangalore, India.
authors.forename: Moni Abraham
authors.initials: MA
authors.lastname: Kuriakose
authors.affiliation: Ganit Labs, Bio-IT Centre, Institute of Bioinformatics and Applied Biotechnology, Biotech Park, Electronic City, Bangalore, India ; Strand Life Sciences, Bellary Road, Hebbal, Bangalore, India.
authors.forename: Binay
authors.initials: B
authors.lastname: Panda
keywords: RNA-seq; gene expression; hypopharynx; larynx; miRNA and promoter hypermethylation; squamous cell carcinoma