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Gene expression profiling of PRAME-positive and PRAME-negative osteosarcoma samples

ABSTRACT: Preferentially Expressed Antigen in Melanoma (PRAME) is frequently overexpressed in a wide variety of cancers and it has been proposed as prognostic marker for clinical outcome. It belongs to a class of non-mutated genes whose expression seems to be mostly restricted to tumor cells. Osteosarcoma is the most common primary malignant bone tumor in children and young adults. Despite advances in the diagnosis and management of osteosarcoma, long-term survival has not envolved substantially in the past decades, justifying efforts in finding effective therapeutic targets. In order to assess transcriptome characteristics that could contribute to further comprehend PRAME association with cancer, the technique of gene expression profiling was used to compare PRAME-positive and PRAME-negative osteosarcoma samples. Keywords: disease state analysis Six tumor samples representing distinct histological classes of osteosarcoma (telangiectatic, giant cell, anaplastic, osteoblastic and chondroblastic) were included in this study. They were obtained from individual patients ranging from 5 to 29 years old. 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 UniSet Human I bioarrays, containing 10,000 human transcripts, were used for all experiments. Hybridization procedures strictly followed protocols provided by the manufacturer (GE Healthcare). A total of 12 arrays were hybridized, including 6 tumor samples (3 PRAME-positive and 3 PRAME-negative) and their respective technical replicates. 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 Patricia

PROVIDER: S-ECPF-GEOD-8079 | biostudies-other |

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 PRAME-positive and PRAME-negative osteosarcoma samples

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