Department of Lymphoma and Breast Cancer, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uyghur Autonomous Region 830011, P.R. China.
Mol Med Rep. 2017 Oct;16(4):4685-4693. doi: 10.3892/mmr.2017.7158. Epub 2017 Aug 3.
The current study aimed to explore the mechanisms associated with classic Hodgkin lymphoma (cHL) to identify novel diagnostic and therapeutic targets. The GES12453 microarray dataset was downloaded from the Gene Expression Omnibus database; the differentially expressed genes (DEGs) between cHL samples and normal B cell samples by were identified using the limma package. Gene ontology (GO) and pathway enrichment analysis of DEGs gene were performed. Furthermore, construction and analysis of protein‑protein interaction (PPI) network was performed, and co‑expression modules of DEGs were produced. A total of 450 DEGs were identified, comprising 216 upregulated and 234 downregulated genes in cHL compared with normal B cell samples. The DEGs were enriched in biological processes associated with immune response. The upregulated genes were mainly associated with the pathway of transcriptional misregulation in cancer, while downregulated genes were associated with B cell receptor signaling. PPI network analysis demonstrated that IL6 had the highest connectivity degree. Interleukin‑6 (IL6) and signal transducer and activator of transcription 1 (STAT1) were demonstrated to be involved with the response to cytokine GO term in co‑expression module 1. Spleen tyrosine kinase (SYK), B‑cell linker protein (BLNK), CD79B, phospholipase C γ2 (PLCG2) were enriched in the B cell receptor signaling pathway in module 2. Matrix metallopeptidase 9 (MMP9), protein tyrosine phosphatase receptor type C had the highest connectivity degrees in module 3 and module 4, respectively. The results suggested that DEGs, including IL6, STAT1, MMP9, SYK, BLNK, PLCG2 and CD79B, and the pathways of B cell receptor signaling, Epstein‑Barr virus infection and transcriptional misregulation in cancer have strong potential to be useful as targets for diagnosis or treatment of cHL.
本研究旨在探讨与经典霍奇金淋巴瘤（cHL）相关的机制，以确定新的诊断和治疗靶点。从基因表达综合数据库中下载 GES12453 微阵列数据集；使用 limma 包鉴定 cHL 样本与正常 B 细胞样本之间的差异表达基因（DEGs）。对 DEGs 基因进行基因本体（GO）和通路富集分析。此外，还进行了蛋白质-蛋白质相互作用（PPI）网络的构建和分析，并产生了 DEGs 的共表达模块。共鉴定出 450 个 DEGs，其中与正常 B 细胞样本相比，cHL 中 216 个上调和 234 个下调。DEGs 富集于与免疫反应相关的生物学过程。上调基因主要与癌症转录调控途径相关，而下调基因与 B 细胞受体信号相关。PPI 网络分析表明，IL6 具有最高的连接度。白细胞介素 6（IL6）和信号转导和转录激活因子 1（STAT1）在共表达模块 1 中被证明与细胞因子 GO 术语的反应有关。脾脏酪氨酸激酶（SYK）、B 细胞连接蛋白（BLNK）、CD79B、磷脂酶 C γ2（PLCγ2）在模块 2 中富集于 B 细胞受体信号通路。模块 3 和模块 4 中基质金属蛋白酶 9（MMP9）和蛋白酪氨酸磷酸酶受体 C 具有最高的连接度。结果表明，包括 IL6、STAT1、MMP9、SYK、BLNK、PLCγ2 和 CD79B 在内的 DEGs 以及 B 细胞受体信号通路、Epstein-Barr 病毒感染和转录调控失调等途径，具有作为 cHL 诊断或治疗靶点的巨大潜力。
