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Diffuse large B-cell lymphoma (DLBC) is a kind of tumor with rapid progress and poor prognosis. Therefore, it is necessary to explore new biomarkers or therapeutic targets to assist in diagnosis or treatment. This study is aimed at screening hub genes by weighted gene coexpression network analysis (WGCNA) and exploring the significance of overall survival (OS) in DLBC patients. Statistical data using WGCNA to analyze mRNA expression in DLBC patients came from The Cancer Genome Atlas (TCGA) dataset. After analyzing with clinical information, the biological functions of hub genes were detected. Survival analysis, Cox regression detection, and correlation analysis of the hub genes were carried out. The potential function of the hub gene related to prognosis was predicted by gene set enrichment analysis (GSEA). The results showed that  APOE ,  CTSD ,  LGALS2 , and  TMEM176B  expression in normal tissues was significantly higher than that in cancer tissues ( P  < 0.01). Survival analysis showed that patients with high  APOE  and  CTSD  were associated with better OS ( P  < 0.01).  APOE  and  CTSD  genes were mainly enriched in the regulation of ROS and oxidative stress. The two hub genes related to the prognosis of DLBC were identified and verified based on WGCNA. Survival analysis showed that the overexpression of  APOE  and  CTSD  in DLBC might be beneficial to the prognosis. These findings identified vital pathways and genes that may become new therapeutic targets and contribute to prognostic indicators.

Hub Gene and Its Key Effects on Diffuse Large B-Cell Lymphoma by Weighted Gene Coexpression Network Analysis