Zhang Shuo, Wang Hongmin, Liu Aichun
Department of Haemolymph, Harbin Medical University Cancer Hospital, Harbin, China.
Department of Hematology, the First Hospital of Qiqihar, Qiqihar, China.
Ann Transl Med. 2022 Oct;10(20):1136. doi: 10.21037/atm-22-4709.
Copy number variations (CNVs) participate in the development and progression of cancer by altering the expression levels of genes. However, it is unclear whether this correlation exists in diffuse large B-cell lymphoma (DLBCL).
Differentially expressed genes (DEGs) were identified from the GSE25638 and GSE56315 datasets. Modules that were highly related to DLBCL prognosis were obtained by Weighted Gene Co-expression Network Analysis (WGCNA). We performed an integrated analysis between CNV and differential gene expression in The Cancer Genome Atlas (TCGA) DLBCL. The DEGs were then overlapped with the module genes and expression-copy number variations-related (Exp-CNV-related) genes to obtain the common key genes. Time-dependent receiver operating characteristic (ROC) analysis was utilized to evaluate the accuracy of the key gene in predicting the prognosis of DLBCL. Next, we conducted a Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to explore the key gene. The potential molecule drugs of the key gene were identified by Connectivity Map (Cmap) analysis.
A turquoise module with 160 genes was identified as the signature module. ATP1B1 is overexpressed in DLBCL cell lines, compared to Cluster of Differentiation 19+B (CD19+B) cells. The ROC curve indicated that ATP1B1 could be a biomarker for diagnosing DLBCL, and the forest map suggested that gene expression levels had a greater impact on the prognosis of patients with DLBCL. The area under curve (AUC) value of the time-dependent ROC curve with values based on the 1-, 3-, and 5-year survivability were 0.576, 0.663, and 0.706, respectively. Pathway analysis demonstrated the relationship between ATP1B1 and focal adhesion, etc. The inhibitory effects of ATP1B1 downregulation on DLBCL cell proliferation, cell migration, invasion, and cell adhesion were also examined. We found out that the higher proliferation ability in ATP1B1-overexpression cells was rescued with roxithromycin.
ATP1B1 is a copy number driver gene that could potentially be adopted as a diagnostic biomarker and therapeutic target of DLBCL.
拷贝数变异（CNV）通过改变基因表达水平参与癌症的发生和发展。然而，这种相关性在弥漫性大B细胞淋巴瘤（DLBCL）中是否存在尚不清楚。
从GSE25638和GSE56315数据集中鉴定差异表达基因（DEG）。通过加权基因共表达网络分析（WGCNA）获得与DLBCL预后高度相关的模块。我们在癌症基因组图谱（TCGA）DLBCL中进行了CNV与差异基因表达的综合分析。然后将DEG与模块基因和表达-拷贝数变异相关（Exp-CNV相关）基因重叠，以获得共同的关键基因。利用时间依赖性受试者工作特征（ROC）分析评估关键基因预测DLBCL预后的准确性。接下来，我们进行了京都基因与基因组百科全书（KEGG）分析以探索关键基因。通过连接图谱（Cmap）分析确定关键基因的潜在分子药物。
一个包含160个基因的绿松石模块被鉴定为特征模块。与分化簇19+B（CD19+B）细胞相比，ATP1B1在DLBCL细胞系中过表达。ROC曲线表明ATP1B1可能是诊断DLBCL的生物标志物，森林图表明基因表达水平对DLBCL患者的预后有更大影响。基于1年、3年和5年生存率的值的时间依赖性ROC曲线的曲线下面积（AUC）值分别为0.576、0.663和0.706。通路分析证明了ATP1B1与粘着斑等之间的关系。还研究了ATP1B1下调对DLBCL细胞增殖、细胞迁移、侵袭和细胞粘附的抑制作用。我们发现罗红霉素挽救了ATP1B1过表达细胞中较高的增殖能力。
ATP1B1是一个拷贝数驱动基因，有可能被用作DLBCL的诊断生物标志物和治疗靶点。
