Abstract
Metastatic melanoma is an aggressive skin cancer and is one of the global malignancies with high mortality and morbidity. It is essential to identify and verify diagnostic biomarkers of early metastatic melanoma. Previous studies have systematically assessed protein biomarkers and mRNA-based expression characteristics. However, molecular markers for the early diagnosis of metastatic melanoma have not been identified. To explore potential regulatory targets, we have analyzed the gene microarray expression profiles of malignant melanoma samples by co-expression analysis based on the network approach. The differentially expressed genes (DEGs) were screened by the EdgeR package of R software. A weighted gene co-expression network analysis (WGCNA) was used for the identification of DEGs in the special gene modules and hub genes. Subsequently, a protein-protein interaction network was constructed to extract hub genes associated with gene modules. Finally, twenty-four important hub genes (RASGRP2, IKZF1, CXCR5, LTB, BLK, LINGO3, CCR6, P2RY10, RHOH, JUP, KRT14, PLA2G3, SPRR1A, KRT78, SFN, CLDN4, IL1RN, PKP3, CBLC, KRT16, TMEM79, KLK8, LYPD3 and LYPD5) were treated as valuable factors involved in the immune response and tumor cell development in tumorigenesis. In addition, a transcriptional regulatory network was constructed for these specific modules or hub genes, and a few core transcriptional regulators were found to be mostly associated with our hub genes, including GATA1, STAT1, SP1, and PSG1. In summary, our findings enhance our understanding of the biological process of malignant melanoma metastasis, enabling us to identify specific genes to use for diagnostic and prognostic markers and possibly for targeted therapy.
Highlights
Melanoma, known as malignant melanoma, is a type of cancer that develops from cells with different degrees of pigmentation, including melanotic and amelanotic melanocytes [1]
To improve the reliability of the analysis, microarray data containing 471 3-level expression data were pretreated and combined into two global datasets of both primary tumor tissue (TP) and melanoma malignant metastatic tumor (MT) tissue obtained from the Genomic Data Commons database (GDC) database
Compared with primary solid tumor samples, 639 down-regulated genes and 929 upregulated genes were identified in the metastatic melanoma samples (P-value < 0.01, log2 fold change > 1) (Fig 1B)
Summary
Known as malignant melanoma, is a type of cancer that develops from cells with different degrees of pigmentation, including melanotic and amelanotic melanocytes [1]. Potential diagnostic biomarkers of metastatic melanoma ultraviolet light [2]. Metastatic melanoma is uncommon but aggressive, with high mortality rates [3], and is the most dangerous type of skin cancer. There were 23.2 million new skin cancer cases in 2012 [2]. The incidence of melanoma is estimated to be between 3% and 7%; based on these estimates, the incidence of melanoma will double every 10–20 years [5]
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