Identification of oxidative stress-related hub genes for predicting prognosis in diffuse large B-cell lymphoma

Background: Oxidative stress is a cellular characteristic that might induce the proliferation and differentiation of tumor cells and promote tumor progression in diffuse large B-cell lymphoma (DLBCL).

Methods: The DLBCL gene sequencing dataset, tumor mutation burden data, copy number variation data of Somatic cell mutation data in TCGA were downloaded for data training analysis, along with four DLBCL datasets in GEO for validation analysis. The known oxidative stress related genes (OSRGs) were collected from websites. The weighted gene co-expression network analysis (WGCNA) was conducted on the TCGA DLBCL dataset to obtain gene modules related to oxidative stress and intersected with the known OSRGs to obtain the hub genes, which were used to perform consensus clustering on the samples to obtain new phenotypes. Next, the prognosis related OSRGs were selected through regression analysis algorithms and key genes were identified. These genes were used to establish the prognostic risk model and predictive model, and to compare functional and pathway differences among different risk groups.

Results: Through website search, we obtained 297 known OSRGs, and after intersecting with WGCNA results, we obtained 26 OSRGs. The TCGA-DLBC samples were clustered into 2 subtypes with these genes and there were significant differences in immune infiltration between subtypes. After regression analysis, we obtained a total of four key genes, BMI1, CDKN1A, NOX1, and SESN1. The risk prediction model established with these four genes as variables has accurate prognostic prediction ability. The key genes interact with 65 miRNAs, 57 TFs, 47 RBPs, and 62 drugs, respectively, and are closely related to immune infiltration of the disease. Among them, CDKN1A and SESN1 had the highest variability.

Conclusions: The key genes involved in oxidative stress could predict the prognosis of DLBCL and potentially become therapeutic targets.