Abstract 4253: Differential expression of protein-coding and non-coding RNAs in malignant melanoma

Abstract

Abstract Background: Skin cancer is the most common malignancy in the United States. Although melanoma makes less than 10% of diagnosed skin cancers, it is responsible for most skin cancer-related deaths due to high metastatic potential and therapeutic resistance. Therefore, research is needed to find suitable biomarkers that could improve early diagnosis, prognosis and/or therapy of cutaneous melanoma. In this study, we aim to identify differentially expressed genes in melanoma patients which can serve as potential biomarkers for this disease. Methods: Gene expression profiling was carried out using GEPIA (http://gepia.cancer-pku.cn/index.html), a bioinformatics research platform for the profiling and interactive analysis of cancerous gene expression based on The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Differentially expressed transcripts were classified as protein-coding or non-coding. The list of differentially expressed protein-coding genes was subjected to Functional and Pathway enrichment analysis using the online Database for Annotation, Visualization and Integrated Discovery (DAVID; https://david.ncifcrf.gov). Non-coding RNAs (ncRNAs) were searched in Medline database to determine previous association of specific ncRNAs to melanoma. Results: A total of 107 transcripts were found upregulated in melanoma compared to normal tissues; 58 were identified as protein-coding RNAs, 48 as ncRNAs, and one as novel transcript. DAVID analysis of differentially expressed protein-coding RNAs demonstrated that upregulated transcripts were significantly enriched in oxidation-reduction processes, melanin biosynthetic process, visual perception, and melanosome organization. To identify novel genes not previously reported in melanoma, a Medline search was performed for transcripts with the highest over-expression in melanoma compared to normal skin tissue. Of the protein-coding RNAs, 33 were previously reported in melanoma, including PMEL, TYR, MLANA, among others, thus validating our results. However, the remaining 25 protein-coding genes were not previously associated to melanoma. In contrast, most of the ncRNAs have not been previously mentioned in melanoma; some of these ncRNAs were specifically expressed in melanoma but not in other cancer types or normal skin. Kaplan-Meier survival analysis of differentially expressed transcripts identified eleven protein-coding and nine non-coding RNAs whose expression levels were significantly associated with overall survival in melanoma patients. Conclusions: Analysis of differential gene expression between melanoma and normal skin tissue using GEPIA tool to mine data from TCGA and GTEx databases allowed identification of protein-coding and non-protein coding genes that may be involved in cutaneous malignant transformation, and identification of novel genes that may be potential biomarkers for this disease. Citation Format: Stephanie Figueroa, Raj Tiwari, Jan Geliebter, Niradiz Reyes. Differential expression of protein-coding and non-coding RNAs in malignant melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4253.