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Predictors of the response to chemoradiotherapy in SCC of larynx

ABSTRACT: Laryngeal and hypopharyngeal squamous cell carcinoma was histopathologically confirmed on 35 samples obtained by incisional biopsy. Total RNAs from frozen specimens were isolated using Trizol reagent (Invitrogen Corporation, Carlsbad, CA) according to the manufacturer protocol. RNA quality was verified by electrophoresis through agarose gel upon visualization with ethidium bromide and only RNA samples with a ratio >1 for 28S/18S ribosomal RNA were further processed. A two-round RNA amplification procedure was carried out. Normal larynx and hypopharynx samples was used as reference for hybridizations, these samples were processed in the same manner as tumor samples. Amplified RNA were then used in a transcriptase reverse reaction into cDNA in the presence of Cy3- or Cy5-labeled dCTP Keywords: other

ORGANISM(S): Homo sapiens

PROVIDER: GSE2465 | GEO | 2005/05/09

SECONDARY ACCESSION(S): PRJNA91173

REPOSITORIES: GEO

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Project description:Cancers of the upper aero-digestive tracts (oral cavity, pharynx and larynx) are the sixth most common cancer worldwide. Laryngo-pharyngeal squamous cell carcinomas are one of the most common cancers in this category. Despite recent advances in the field of cancer research using high-throughput tools, the information, especially on tumors of hypopharynx, is relatively scarce. We have used next-generation sequencing and computational biology to study both the genes and miRNA from laryngo-pharyngeal tumors. 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 subsites of head and neck. 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. RNA-seq experiments in tumors of larynx and hypopharynx for discovery of gene and miRNA expression Please note that processed data files were not provided since they are available through the journal's website. However a brief description of each processed data is provided in the 'readme.txt'.

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Predictors of the response to chemoradiotherapy in SCC of larynx

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