A meta‑analysis of transcriptome datasets characterizes malignant transformation from melanocytes and nevi to melanoma

Abstract

Melanoma represents one of the most aggressive malignancies and has a high tendency to metastasize. The present study aims to investigate the molecular mechanisms of two pathways to cancer transformation with the purpose of identifying potential biomarkers. Our approach is based on a meta-analysis of gene expression profiling contrasting two scenarios: A model that describes a transformation pathway from melanocyte to melanoma and a second model where transformation occurs through an intermediary nevus. Data consists of three independent, publicly available microarray datasets from the Gene Expression Omnibus (GEO) database comprising samples from melanocytes, nevi and melanoma. The present analysis identified 808 differentially expressed genes (528 upregulated and 360 downregulated) in melanoma compared with nevi, and 2,331 differentially expressed genes (946 upregulated and 1,385 downregulated) in melanoma compared with melanocytes. Further analysis narrowed down this list, since 682 differentially expressed genes were found in both models (417 upregulated and 265 downregulated). Enrichment analysis identified relevant dysregulated pathways. This article also presented a discussion on significant genes including ADAM like decysin 1, neudesin neurotrophic factor, , apolipoprotein L6, motif chemokine ligand ()8, basic, immunoglobulin-like variable motif containing and . These are of particular interest because they encode secreted proteins hence represent potential blood biomarkers for the early detection of malignant transformation in both scenarios. Cytotoxic T-lymphocyte associated protein 4, an important therapeutic target in melanoma treatment, was also upregulated in both comparisons indicating a potential involvement in immune tolerance, not only at advanced stages but also during the early transformation to melanoma. The results of the present study may provide a research direction for studying the mechanisms underlying the development of melanoma, depending on its origin.

Metastatic Melanoma: Liquid Biopsy as a New Precision Medicine Approach

“…The less favorable prognoses are obviously linked to the more advanced stages of the disease. In recent years, many studies have shed light on the mechanisms underlying melanoma development and have shown that the melanocytes tumor transformation process is complex and multi-stage [ 19 , 20 ]. It is clear that the most benign lesions present the alteration of v-Raf murine sarcoma viral oncogene homolog B (BRAF) in the codon V600E (that is sufficient for the nevus formation), but for melanoma development, BRAF mutation is not sufficient because the disease progression is bound to concomitant alteration in other genes involved in the most important cellular processes [ 21 , 22 ].…”

Regulation of LncRNAs in Melanoma and Their Functional Roles in the Metastatic Process

“…In recent years, several large-scale transcriptomic and genomic studies have identified deregulated lncRNAs in melanomas [60,61]. In a study using a collection of 7256 RNAsequencing libraries from 27 tissues and cancer types, 339 lncRNAs were associated with melanoma [62].…”

Chemokine Pathways in Cutaneous Melanoma: Their Modulation by Cancer and Exploitation by the Clinician

“…Immunohistochemistry and genetic studies, as well as analyses of patient serum, have highlighted these differences and could be incorporated to aid diagnosis. For example, malignant melanomas express higher levels of CXCL1, CXCL2, and CXCL8 and receptors CXCR1, CXCR4, CCR10, and CCR7 compared with benign naevi [ 108 , 109 , 110 , 111 ]. The expression of chemokines such as CXCL8 and its receptor CXCR2 increase as the tumour transitions from the radial to the vertical growth phase [ 24 ].…”