PHOSPHO1 Serves as a Key Metabolism-Related Biomarker in the Tumorigenesis of Diffuse Large B-cell Lymphoma

Objective: Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of non-Hodgkin lymphoma. Due to its genetic heterogeneity and abnormal metabolism, many DLBCL patients have a poor prognosis. This study investigated the key metabolism-related genes and potential mechanisms. Methods: Differentially expressed genes, differentially expressed transcription factors (TFs), and differentially expressed metabolism-related genes (DEMRGs) of glucose and lipid metabolic processes were identified using the edgeR package. Key DEMRGs were screened by Lasso regression, and a prediction model was constructed. The cell type identification by estimating relative subsets of RNA transcripts algorithm was utilized to assess the fraction of immune cells, and Gene Set Enrichment Analysis was used to determine immune-related pathways. A regulatory network was constructed with significant co-expression interactions among TFs, DEMRGs, immune cells/pathways, and hallmark pathways. Results: A total of 1551 DEMRGs were identified. A prognostic model with a high applicability (area under the curve=0.921) was constructed with 13 DEMRGs. Tumorigenesis of DLBCL was highly related to the neutrophil count. Four DEMRGs (PRXL2AB, CCN1, DECR2 and PHOSPHO1) with 32 TF—DEMRG, 36 DEMRG—pathway, 14 DEMRG—immune-cell, 9 DEMRG—immune-gene-set, and 67 DEMRG—protein-chip interactions were used to construct the regulatory network. Conclusion: We provided a prognostic prediction model based on 13 DEMRGs for DLBCL. We found that phosphatase, orphan 1 (PHOSPHO1) is positively regulated by regulatory factor X5 (RFX5) and mediates MYC proto-oncogene (MYC) targeting the V2 pathway and neutrophils.