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Gene expression profiling of oral squamous cell carcinoma

ABSTRACT: Oral squamous cell carcinoma (OSCC) is a solid neoplasm exhibiting aggressive tumor phenotypes with unpredictable biological behavior and usually a very unfavorable prognosis. The comprehension of the molecular basis of the variability within this cancer disease should lead to the development of satisfactory targeted therapies as well as to improvements in diagnosis specificity and sensitivity. Due to the lack of definite molecular concepts in OSCC, this study aimed to detail molecular characteristics possibly reflecting differences in tumor progression mechanisms through genome-wide gene expression profiles. Keywords: disease-state analysis Nine tumor samples differing in their TNM classification and their respective surgical margins were used in this study. They were obtained from individual patients during tongue and floor of the mouth tumor resection surgery. Microarray experiments were carried out using the microarray platform CodeLink (GE Healthcare). This platform utilizes bioarrays consisting of 30-base, single pre-validated oligonucleotide probe per gene target. CodeLink Whole-Genome bioarrays, containing 55,000 human transcripts, were used for all experiments. Hybridization procedures strictly followed protocols provided by the manufacturer (GE Healthcare). A total of 11 arrays were hybridized in this study. Arrays were scanned following the recommended scanning procedure and settings for use with CodeLink bioarrays (GE Healthcare) on GenePix 4000B Array Scanner/GenePix Pro 4.0 software (Axon Instruments).

ORGANISM(S): Homo sapiens

SUBMITTER: Severino P

PROVIDER: S-ECPF-GEOD-9792 | biostudies-other | 2008

REPOSITORIES: biostudies-other

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Project description:Background: HPV-positive oral squamous cell carcinomas (OSCCs) are specific biological and clinical entities, characterized by a more favorable prognosis compared to HPV-negative OSCCs and occurring generally in non-smoking and non-drinking younger individuals. However, poor information is available on the molecular and the clinical behavior of HPV-positive oral cancers occurring in smoking/drinking subjects. Thus, this study was designed to compare, at molecular level, two OSCC cell lines, both derived from drinking and smoking individuals and differing for presence/absence of HPV infection. Methods: HPV-negative UPCI-SCC-131 and HPV16-positive UPCI-SCC-154 cell lines were compared by whole genome gene expression profiling and subsequently studied for activation of Wnt/βCatenin signaling pathway by the expression of several Wnt-target genes, βCatenin intracellular localization, stem cell features and miRNA let-7e. Gene expression data were validated in head and neck squamous cell carcinoma (HNSCC) public datasets. Results: Gene expression analysis identified Wnt/βCatenin pathway as the unique signaling pathway more active in HPV-negative compared to HPV-positive OSCC cells and this observation was confirmed upon evaluation of several Wnt-target genes (i.e., Cyclin D1, Cdh1, Cdkn2a, Cd44, Axin2, c-Myc and Tcf1). Interestingly, HPV-negative OSCC cells showed higher levels of total βCatenin and its active form, increase of its nuclear accumulation and more prominent stem cell traits. Furthermore, miRNA let-7e was identified as potential upstream regulator responsible for the downregulation of Wnt/βCatenin signaling cascade since its silencing in UPCI-SCC-154 cell resulted in upregulation of Wnt-target genes. Finally, the analysis of two independent gene expression public datasets of human HNSCC cell lines and tumors confirmed that Wnt/βCatenin pathway is more active in HPV-negative compared to HPV-positive tumors derived from individuals with smoking habit. Conclusions: These data suggest that lack of HPV infection is associated with more prominent activation of Wnt/βCatenin signaling pathway and gain of stem-like traits in tobacco-related OSCCs.

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Gene expression profiling of oral squamous cell carcinoma

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