Network-based co-expression analysis for exploring the potential diagnostic biomarkers of metastatic melanoma

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.

Alterations in patient plasma microRNA expression profiles following resection of metastatic melanoma

“…A third PPI of interest is indicated by the generated String network between Argonaute 3 and SP1, in the presence of miR‐150‐5p, supported experimental data, co‐expression data, data from curated databases, and textmining. SP1 has been previously identified as a core transcriptional regulator in metastatic melanoma, associated with regulation of 24 differentially expressed hub genes involved in the immune response, tumor cell development, and tumorigenesis in melanoma . This suggests a potential regulatory role for miR‐150‐5p on differentially expressed genes in the setting of metastatic melanoma through interaction with SP1 via Argonaute 3.…”

Novel Oxidative Stress-related Prognostic Biomarkers for Melanoma Associated With Tumor Metastasis

“…Melanoma is one of the most common skin malignancies, and poor patient prognosis is signi cantly associated with its high metastatic capacity [44]. Although many novel diagnostic techniques and molecular biomarkers have been discovered in recent years, they have not su ciently improved early diagnosis and prognosis of SKCM [11]. Therefore, it is imperative to identify SKCM prognosis-related molecules and the exact mechanism of cancer metastasis.…”

“…However, therapeutic effectiveness remains limited due to lack of knowledge regarding the intricate mechanism underlying SKCM metastasis. In recent years, many studies have focused on identifying potential biomarkers for metastatic melanoma [11,12]. Unfortunately, these developments have been inadequate for improving early diagnosis and prognosis of SKCM.…”

Assessing immune infiltration and the tumor microenvironment for the diagnosis and prognosis of sarcoma

“…P2RY10 belongs to the family of G -protein -coupled receptors, which are activated by adenosine and uridine [63]. Wang et al found that P2RY10 was potentially involved in the immune response and the development of sarcomas [64]. RASL3, a novel member of the RasGAP Rasal family, is predominantly expressed by T cells [65,66], and RasGAP activity stimulates ERK phosphorylation.…”