Abid Junaid, Al-Rawi Mahmood Basil A, Mahmood Ahmad, Li An, Jiang Tiemin
State Key Laboratory of Food Nutrition and Safety, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, 300222, China.
Department of Optometry, College of Applied Medical Sciences, King Saud University, Riyadh, 11433, Saudi Arabia.
Hereditas. 2025 Mar 24;162(1):45. doi: 10.1186/s41065-025-00411-w.
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.
弥漫性大B细胞淋巴瘤（DLBC）是非霍奇金淋巴瘤最常见的亚型，其特点是具有侵袭性，晚期预后较差。尽管治疗取得了进展，但驱动DLBC进展的分子机制仍未完全了解，因此需要鉴定用于诊断和预后的新型生物标志物。在本研究中，我们分析了来自基因表达综合数据库（GEO）的两个公开可用数据集（GSE32018和GSE56315），以鉴定重叠的差异表达基因（DEG）。随后，采用了全面的计算机模拟和体外方法来解读所鉴定的DEG在DLBC中的作用。对GSE32018和GSE56315数据集的DEG分析确定了五个重叠基因：SP3、CSNK1A1、STYX、SIRT5和MGEA5。使用GEPIA2数据库进行的表达验证证实，与正常对照相比，DLBC组织中SP3、CSNK1A1、STYX和SIRT5上调，而MGEA5下调。此外，突变分析显示CSNK1A1是这些DEG中唯一出现突变的基因，在DLBC患者中的突变频率为2.7%。甲基化分析突出了DEG甲基化水平与mRNA表达之间的负相关，而生存分析确定高STYX表达与DLBC患者较差的总生存期显著相关。功能测定表明，U2932细胞中STYX的敲低导致细胞增殖、集落形成减少，伤口愈合增强，表明STYX在DLBC细胞存活和迁移中起关键作用。此外，基因富集分析揭示了这些DEG参与关键生物学过程，包括细胞内运输和髓系祖细胞分化。这些发现强调了SP3、CSNK1A1、STYX、SIRT5和MGEA5作为DLBC生物标志物和治疗靶点的潜力，尤其突出了STYX作为有前景的预后标志物和治疗干预潜在靶点的地位。
