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: Jayalakshmi Nair, Prachi Jain, Udita Chandola, Vinayak Palve, N R Harsha Vardhan, Ram Bhupal Reddy, Vikram D Kekatpure, Amritha Suresh, Moni Abraham Kuriakose, Binay Panda
• Journal: Genes & cancer (Genes Cancer) Vol. 6 Issue 7-8 Pg. 328-40 (Jul 2015) ISSN: 1947-6019 [Print] United States
• PMID: 26413216 (Publication Type: Journal Article)