Gene and miRNA expression changes in squamous cell carcinoma of larynx and hypopharynx
Jayalakshmi Nair1, Prachi Jain1, Udita Chandola1, Vinayak Palve1, N R. Harsha Vardhan2, Ram Bhupal Reddy2, Vikram D. Kekatpure2, Amritha Suresh2, Moni Abraham Kuriakose2 and Binay Panda1,3
1 Ganit Labs, Bio-IT Centre, Institute of Bioinformatics and Applied Biotechnology, Biotech Park, Electronic City, Bangalore, India
2 Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Centre, Narayana Hrudayalaya, Bangalore, India
3 Strand Life Sciences, Bellary Road, Hebbal, Bangalore, India
Correspondence:
Binay Panda, email:
Keywords: RNA-seq, squamous cell carcinoma, larynx, hypopharynx, gene expression, miRNA and promoter hypermethylation
Received: April 13, 2015 Accepted: June 9, 2015 Published: June 10, 2015
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.
