Dataset Information

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.

SUBMITTER: Nair J

PROVIDER: S-EPMC4575920 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Gene and miRNA expression changes in squamous cell carcinoma of larynx and hypopharynx.

Nair Jayalakshmi J Jain Prachi P Chandola Udita U Palve Vinayak V Vardhan N R Harsha NR Reddy Ram Bhupal RB Kekatpure Vikram D VD Suresh Amritha A Kuriakose Moni Abraham MA Panda Binay B

Genes & cancer 20150701 7-8

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 ...[more]

PMID: 26413216

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Project description:AimTo compare the efficacy of two altered fractionation radiotherapy treatment protocols (hyperfractionation and accelerated fractionation with concomitant boost) with conventional fractionation in improvement of locoregional disease control and survival of patients with squamous cell carcinoma of the larynx, oropharynx, or hypopharynx.MethodsFrom March 1999 to December 2000, 51 patients with previously untreated squamous cell carcinoma of the larynx, oropharynx or hypopharynx underwent conventionally fractionated radiotherapy and received 66-70 Gy in 6(1/2)-7 weeks (2 Gy per fraction a day, 5 fractions a week). From January 2001 to June 2004, 101 patients with the same diagnoses underwent either hyperfractionated radiotherapy, with 74.4-79.2 Gy delivered in 6.2-7 weeks (1.2 Gy per fraction twice a day), or accelerated fractionation with concomitant boost, which delivered 68.7-72 Gy in 6 weeks (1.8 Gy per fraction a day and 1.5 Gy per fraction a day to a boost filed as a second daily treatment for the last 11-12 treatment days). Locoregional relapse and overall survival were recorded.ResultsComplete response to treatment was obtained in 31 of 51 patients treated with conventional fractionation, 33 of 50 patients treated with hyperfractionation, and 36 of 51 patients treated with accelerated fractionation. No significant differences were observed among the patients treated with conventional, hyperfractionated, or accelerated radiotherapy modalities either in locoregional control rate (41% vs 35% vs 49%, respectively; P=0.690) or overall survival rate (50% vs 40% vs 51%, respectively; P=0.760). The grade of acute reactions of the larynx significantly differed among the treatment groups (Fisher exact test; P=0.039). The difference in the grade of acute side effects in the skin among the treatment groups was of borderline significance (chi2(2) test; P=0.054). There was also a borderline difference among the groups in the grade of late side effects in the mucous membrane (chi2(2) test; P=0.055).ConclusionAltered fractionation regimens were not more efficacious than conventional fractionation in the treatment of previously untreated head and neck carcinoma.Clinical trial registrationClinicalTrials.gov Identifier: NCT00291434.

Project description:Simple Summary Penile squamous cell carcinoma (PSCC) is the most common type of penile cancer (PeCa) and is associated with human papillomavirus (HPV) in about 50% of cases. It is of high clinical impact to identify patients who are at high risk of metastasis and are likely to benefit from adjuvant therapies. Today, valid prognostic biomarkers are scarce in penile cancer. In the present study, we attempted to identify miRNAs involved in tumor development and metastasis in distinct histological subtypes with or without HPV infection in PSCC patients. We confirmed that specific miRNAs could serve as potential diagnostic and prognostic markers in single PSCC subtypes and are associated with HPV infection. Abstract Although microRNAs are described as promising biomarkers in many tumor types, little is known about their role in PSCC. Thus, we attempted to identify miRNAs involved in tumor development and metastasis in distinct histological subtypes considering the impact of HPV infection. In a first step, microarray analyses were performed on RNA from formalin-fixed, paraffin-embedded tumor (22), and normal (8) tissue samples. Microarray data were validated for selected miRNAs by qRT-PCR on an enlarged cohort, including 27 tumor and 18 normal tissues. We found 876 significantly differentially expressed miRNAs (p ≤ 0.01) between HPV-positive and HPV-negative tumor samples by microarray analysis. Although no significant differences were detected between normal and tumor tissue in the whole cohort, specific expression patterns occurred in distinct histological subtypes, such as HPV-negative usual PSCC (95 differentially expressed miRNAs, p ≤ 0.05) and HPV-positive basaloid/warty subtypes (247 differentially expressed miRNAs, p ≤ 0.05). Selected miRNAs were confirmed by qRT-PCR. Furthermore, microarray data revealed 118 miRNAs (p ≤ 0.01) that were significantly differentially expressed in metastatic versus non-metastatic usual PSCC. The lower expression levels for miR-137 and miR-328-3p in metastatic usual PSCC were validated by qRT-PCR. The results of this study confirmed that specific miRNAs could serve as potential diagnostic and prognostic markers in single PSCC subtypes and are associated with HPV-dependent pathways.

Dataset Information

Gene and miRNA expression changes in squamous cell carcinoma of larynx and hypopharynx.

Publications

Gene and miRNA expression changes in squamous cell carcinoma of larynx and hypopharynx.

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