ENO1-Related Gene Signature Predicts Prognosis and Therapeutic Response in Diffuse Large B-Cell Lymphoma

Wenli Yan¹Xiaoxi Liu²Beibei Gao¹Shanshan Zhang¹Jinhong Ren³Yang Lu⁴Limei Ai²Jinsong Yan¹Haina Wang^1*

• ¹Second Affiliated Hospital of Dalian Medical University, Dalian, China
• ²First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
• ³Shanxi University of Chinese Medicine, Taiyuan, China
• ⁴Chaoyang Central Hospital, Chaoyang, China

Alpha-enolase (ENO1), the enzyme catalyzing 2-phosphoglycerate conversion to phosphoenolpyruvate, is highly expressed in diffuse large B-cell lymphoma (DLBCL) and correlates with adverse clinical outcomes. Thus, understanding the relationship between ENO1-related gene (ERG) network and DLBCL is imperative. Here, we integrated multi-omics profiling (RIP-seq, RNA-seq, and protein interactome analysis) to identify ERGs and established a prognostic model by machine learning algorithms. Eleven hub genes (CHERP, SYNE2, INTS1, FAP, MMP9, LRP5, RBM8A, PRMT5, SLC25A6, PABPC4, PSTPIP2) were identified and incorporated in our model. Patients were stratified into high-and low-risk groups, with high-risk cases showing inferior survival and an immunosuppressive tumor immune microenvironment, marked by dysregulated immune checkpoint proteins. Drug sensitivity assays revealed that high-risk patients exhibited enhanced responses to vincristine, etoposide, and oxaliplatin. Notably, PABPC4 emerged as the predominant prognostic determinant. Functional validation confirmed that PABPC4 knockdown significantly suppressed tumor proliferation, clonogenicity, and xenograft growth in vivo. In conclusion, this study successfully established a prognostic model comprising eleven ERGs, accurately predicting DLBCL prognosis, and highlighted the crucial role of PABPC4 as a novel biomarker in regulating DLBCL progression.