Department of Plastic and Esthetic Surgeries, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China.
Mol Med Rep. 2018 Feb;17(2):2907-2914. doi: 10.3892/mmr.2017.8219. Epub 2017 Dec 7.
Gene expression profiles of cutaneous melanoma were analyzed to identify critical genes associated with metastasis. Two gene expression datasets were downloaded from Gene Expression Omnibus (GEO) and another dataset was obtained from The Cancer Genome Atlas (TCGA). Differentially expression genes (DEGs) between metastatic and non‑metastatic melanoma were identified by meta‑analysis. A protein‑protein interaction (PPI) network was constructed for the DEGs using information from BioGRID, HPRD and DIP. Betweenness centrality (BC) was calculated for each node in the network and the top feature genes ranked by BC were selected to construct the support vector machine (SVM) classifier using the training set. The SVM classifier was then validated in another independent dataset. Pathway enrichment analysis was performed for the feature genes using Fisher's exact test. A total of 798 DEGs were identified and a PPI network including 337 nodes and 466 edges was then constructed. Top 110 feature genes ranked by BC were included in the SVM classifier. The prediction accuracies for the three datasets were 96.8, 100 and 94.4%, respectively. A total of 11 KEGG pathways and 13 GO biological pathways were significantly over‑represented in the 110 feature genes, including endometrial cancer, regulation of actin cytoskeleton, focal adhesion, ubiquitin mediated proteolysis, regulation of apoptosis and regulation of cell proliferation. A SVM classifier of high prediction accuracy was acquired. Several critical genes implicated in melanoms metastasis were also revealed. These results may advance understanding of the molecular mechanisms underlying metastasis, and also provide potential therapeutic targets.
分析皮肤黑色素瘤的基因表达谱,以鉴定与转移相关的关键基因。从基因表达综合数据库(GEO)下载了两个基因表达数据集,并从癌症基因组图谱(TCGA)获得了另一个数据集。通过荟萃分析鉴定转移性和非转移性黑色素瘤之间的差异表达基因(DEGs)。使用来自 BioGRID、HPRD 和 DIP 的信息,为 DEGs 构建蛋白质-蛋白质相互作用(PPI)网络。计算网络中每个节点的介数中心度(BC),并选择按 BC 排名的顶级特征基因,使用训练集构建支持向量机(SVM)分类器。然后在另一个独立数据集上验证 SVM 分类器。使用 Fisher 精确检验对特征基因进行通路富集分析。共鉴定出 798 个 DEG,并构建了一个包含 337 个节点和 466 条边的 PPI 网络。BC 排名前 110 的特征基因被纳入 SVM 分类器。三个数据集的预测准确率分别为 96.8%、100%和 94.4%。在 110 个特征基因中,共有 11 个 KEGG 通路和 13 个 GO 生物学通路显著过度表达,包括子宫内膜癌、肌动蛋白细胞骨架调节、焦点粘连、泛素介导的蛋白水解、细胞凋亡调节和细胞增殖调节。获得了一个具有高预测准确性的 SVM 分类器。还揭示了一些与黑色素瘤转移相关的关键基因。这些结果可能有助于深入了解转移的分子机制,并为潜在的治疗靶点提供依据。