Identification and functional characterization of key biomarkers in diffuse large B-cell lymphoma: emphasis on STYX as a prognostic marker and therapeutic target.

Abstract

Diffuse large B-cell lymphoma (DLBC) is the most common subtype of non-Hodgkin lymphoma, characterized by its aggressive nature and poor prognosis in advanced stages. Despite advances in treatment, the molecular mechanisms driving DLBC progression remain incompletely understood, necessitating the identification of novel biomarkers for diagnosis and prognosis. In this study, we analyzed two publicly available datasets (GSE32018 and GSE56315) from the Gene Expression Omnibus database (GEO) to identify overlapping differentially expressed genes (DEGs). Later on, a comprehensive in silico and in vitro methodology was adopted to decipher the role of identify DEGs in DLBC. DEGs analysis of GSE32018 and GSE56315 datasets identified five overlapping gene: SP3, CSNK1A1, STYX, SIRT5, and MGEA5. Expression validation using the GEPIA2 database confirmed the upregulation of SP3, CSNK1A1, STYX, and SIRT5, and the downregulation of MGEA5 in DLBC tissues compared to normal controls. Furthermore, mutational analysis revealed that CSNK1A1 was the only gene among these DEGs to exhibit mutations, with a 2.7% mutation frequency in DLBC patients. Methylation analysis highlighted a negative correlation between DEGs methylation levels and mRNA expression, while survival analysis identified high STYX expression as significantly associated with poorer overall survival in DLBC patients. Functional assays demonstrated that STYX knockdown in U2932 cells led to reduced cell proliferation, colony formation, and enhanced wound healing, indicating STYX's pivotal role in DLBC cell survival and migration. Additionally, gene enrichment analysis revealed the involvement of these DEGs in key biological processes, including intracellular trafficking and myeloid progenitor cell differentiation. These findings emphasize the potential of SP3, CSNK1A1, STYX, SIRT5, and MGEA5 as biomarkers and therapeutic targets in DLBC, particularly highlighting STYX as a promising prognostic marker and potential target for therapeutic intervention.