Guangdong Provincial Key Laboratory of Agro‑Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong 510642, P.R. China.
Mol Med Rep. 2019 Nov;20(5):4013-4022. doi: 10.3892/mmr.2019.10684. Epub 2019 Sep 16.
Testicular seminoma is one of the most common tumours in the field of urology, and its aetiology is still unclear. The aim of the present study was to identify the factors responsible for the development of testicular cancer and to investigate whether mutations in these genes were primarily congenital or acquired. To identify the key genes and miRNAs linked to testicular seminoma, as well as their potential molecular mechanisms, the GSE15220, GSE1818 and GSE59520 microarray datasets were analysed. A total of 5,195 and 1,163 differentially expressed genes (DEGs) were identified after analysing the GSE15220 and GSE1818 datasets, respectively. Among them, 287 genes were common between the two datasets. Of these, 110 were upregulated and 177 were downregulated. Five differentially expressed microRNAs (miRs; DEMs) that were downregulated in seminoma were identified after analysing the GSE59520 dataset. Following protein‑protein interaction network and Gene Ontology analysis, the five nodes with the highest degrees were screened as hub genes. Among them, the high expression of hub genes, such as protein tyrosine phosphatase receptor type C (PTPRC), was associated with worse overall survival. We also predicted the potential target genes of the DEMs. DNA topoisomerase II α (TOP2A), marker of proliferation Ki‑67 (MKI67), PTPRC and ubiquitin conjugating enzyme E2 C were associated with the PI3K/AKT and Wnt/β‑catenin signalling pathways. In addition, hsa‑miR‑650 and hsa‑miR‑665 were associated with the PI3K/AKT and Wnt/β‑catenin signalling pathways. Additionally, TOP2A and MKI67 were strongly associated with the target genes hsa‑miR‑650 and hsa‑miR‑665, respectively. We proposed that the hub genes reported in the present study may have a certain impact on cellular proliferation and migration in testicular seminoma. The roles of these hub genes in seminoma may provide novel insight to improve the diagnosis and treatment of patients with seminoma.
睾丸精原细胞瘤是泌尿外科领域最常见的肿瘤之一，其病因尚不清楚。本研究旨在确定导致睾丸癌发生的因素，并探讨这些基因的突变是先天的还是后天获得的。为了确定与睾丸精原细胞瘤相关的关键基因和 miRNA 及其潜在的分子机制，分析了 GSE15220、GSE1818 和 GSE59520 微阵列数据集。分析 GSE15220 和 GSE1818 数据集后，分别鉴定出 5195 个和 1163 个差异表达基因（DEGs）。其中，两个数据集之间有 287 个共同基因。其中，上调基因 110 个，下调基因 177 个。分析 GSE59520 数据集后，鉴定出 5 个下调的差异表达 microRNA（miR；DEMs）。通过蛋白质-蛋白质相互作用网络和基因本体论分析，筛选出五个节点度最高的节点作为枢纽基因。其中，高表达的枢纽基因，如蛋白酪氨酸磷酸酶受体 C（PTPRC），与总生存不良相关。我们还预测了 DEMs 的潜在靶基因。DNA 拓扑异构酶 IIα（TOP2A）、增殖标志物 Ki-67（MKI67）、PTPRC 和泛素连接酶 E2 C 与 PI3K/AKT 和 Wnt/β-catenin 信号通路相关。此外，hsa-miR-650 和 hsa-miR-665 与 PI3K/AKT 和 Wnt/β-catenin 信号通路相关。此外，TOP2A 和 MKI67 与靶基因 hsa-miR-650 和 hsa-miR-665 分别具有很强的相关性。我们提出，本研究报道的枢纽基因可能对睾丸精原细胞瘤中细胞的增殖和迁移有一定的影响。这些枢纽基因在精原细胞瘤中的作用可能为改善精原细胞瘤患者的诊断和治疗提供新的思路。
