Abstract
BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most prevalent form of non-Hodgkin's lymphoma globally. SPAG5, a mitotic spindle protein, plays a significant role in DLBCL, where its abnormal expression is often associated with tumor growth, chemotherapy resistance, local recurrence, and poor prognosis. METHODS: A comprehensive analysis of SPAG5 expression across various cancer types was conducted using Timer 2.0 and Sanger Box 3.0. Subsequently, the expression levels of SPAG5 in DLBCL were investigated in comparison to normal samples. Receiver operating characteristic (ROC) curve was then generated to evaluate the diagnostic performance of SPAG5 for DLBCL. Furthermore, the functional role of SPAG5 was characterized, and its impact on the immune microenvironment of DLBCL patients was analyzed. Its potential in predicting immune checkpoint status and responses to immunotherapy was also evaluated. RESULTS: SPAG5 expression demonstrated significant heterogeneity across various cancer types, with a marked upregulation in DLBCL. The diagnostic efficacy of SPAG5 was moderate, yielding an area under curve (AUC) of 0.75. SPAG5 exerted a multifaceted influence on DLBCL progression by regulating critical cellular processes, including cell cycle dynamics, chromosomal segregation, and DNA homeostasis. Notably, patients with elevated SPAG5 expression had poorer survival outcomes than those with low expression. Analysis of the tumor immune microenvironment revealed a distinct pattern: high SPAG5 expression correlated with increased infiltration of resting natural killer (NK) cells, while being associated with reduced presence of regulatory T cells (Tregs) and follicular helper T cells (Tfh). CONCLUSION: Our bioinformatics study elucidated the expression profile, diagnostic potential, and prognostic significance of SPAG5 in DLBCL, emphasizing the complex interplay between SPAG5 expression and the tumor immune landscape. Our findings suggested SPAG5 could be a candidate prognostic marker and potential therapeutic target for DLBCL.