Yan Wei, Li Shawn Xiang, Gao Hongyu, Yang Wei
Department of Hematology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110022, P.R. China.
International College, China Medical University, Shenyang, Liaoning 110022, P.R. China.
Oncol Lett. 2019 Mar;17(3):2825-2835. doi: 10.3892/ol.2019.9900. Epub 2019 Jan 8.
B-cell translocation gene 1 (BTG1) is a member of the BTG/transducer of Erb family. The present study evaluated the impact of BTG1 gene expression on the clinical outcome of diffuse large B-cell lymphoma (DLBCL) and investigated potential mechanisms using the Gene Expression Omnibus (GEO) database. The gene expression profile datasets GSE31312, GSE10846, GSE65420 and GSE87371 were downloaded from the GEO database. BTG1 expression and clinicopathological data were obtained from the GSE31312 dataset. In 498 cases, the expression of BTG1 in DLBCL was associated with treatment response (χ=19.020; P<0.001) and International Prognostic Index score (χ=5.320; P=0.025). Using the Kaplan-Meier method, it was identified that the expression of BTG1 was associated with overall survival (OS) and progression-free survival (PFS) times. Univariate and multivariate Cox regression analysis demonstrated that BTG1 was an independent predictive factor for OS and PFS. From the overlapping analysis of 407 BTG1-associated genes and 22,187 DLBCL-associated genes, 401 genes were identified as BTG1-associated DLBCL genes. Pathway analysis revealed that BTG1-associated DLBCL genes were associated with cancer progression and DLBCL signaling pathways. Subsequently, a protein-protein interaction network was constructed of the BTG1-associated genes, which consisted of 235 genes and 601 interactions. Additionally, 24 genes with high degrees in the network were identified as hub genes, which included genes associated with 'ribosome' [ribosomal protein (RP) L11, RPL3, RPS29, RPL19, RPL15 and RPL12], 'cell cycle' (ubiquitin carboxyl extension protein 52, ATM and Ras homolog family member H), 'mitogen-activated protein kinase pathway' (mitogen-activated protein kinase 1), 'histone modification' (ASH1-like protein) and 'transcription/translation' (eukaryotic translation initiation factor 3 subunit E, eukaryotic translation elongation factor 1 δ, transcription termination factor 1, cAMP responsive element binding protein 1 and RNA polymerase II subunit F). In conclusion, BTG1 may serve as a predictive biomarker for DLBCL prognosis. Additionally, bioinformatics analysis indicated that BTG1 may exhibit key functions in the progression and development of DLBCL.
B细胞易位基因1（BTG1）是BTG/Erb转导家族的成员。本研究评估了BTG1基因表达对弥漫性大B细胞淋巴瘤（DLBCL）临床结局的影响，并使用基因表达综合数据库（GEO）调查了潜在机制。从GEO数据库下载了基因表达谱数据集GSE31312、GSE10846、GSE65420和GSE87371。BTG1表达和临床病理数据来自GSE31312数据集。在498例病例中，DLBCL中BTG1的表达与治疗反应（χ=19.020；P<0.001）和国际预后指数评分（χ=5.320；P=0.025）相关。采用Kaplan-Meier法确定，BTG1的表达与总生存期（OS）和无进展生存期（PFS）相关。单因素和多因素Cox回归分析表明，BTG1是OS和PFS的独立预测因素。通过对407个与BTG1相关的基因和22187个与DLBCL相关的基因进行重叠分析，确定了401个基因作为与BTG1相关的DLBCL基因。通路分析显示，与BTG1相关的DLBCL基因与癌症进展和DLBCL信号通路相关。随后，构建了由与BTG1相关的基因组成的蛋白质-蛋白质相互作用网络，该网络由235个基因和601个相互作用组成。此外，网络中24个高连接度基因被确定为枢纽基因，其中包括与“核糖体”相关的基因[核糖体蛋白（RP）L11、RPL3、RPS29、RPL19、RPL15和RPL12]、“细胞周期”相关的基因（泛素羧基末端延伸蛋白52、ATM和Ras同源家族成员H）、“丝裂原活化蛋白激酶通路”相关的基因（丝裂原活化蛋白激酶1）、“组蛋白修饰”相关的基因（ASH1样蛋白）以及“转录/翻译”相关的基因（真核翻译起始因子3亚基E、真核翻译延伸因子1δ、转录终止因子1、cAMP反应元件结合蛋白1和RNA聚合酶II亚基F）。总之，BTG1可能作为DLBCL预后的预测生物标志物。此外，生物信息学分析表明，BTG1可能在DLBCL的进展和发展中发挥关键作用。
