Jia Zhixiang, Zhang Jiayi, Li Zijia, Ai Limei
Department of Hematology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
Department of Hematology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
Int J Biol Macromol. 2024 Dec;282(Pt 3):137117. doi: 10.1016/j.ijbiomac.2024.137117. Epub 2024 Oct 31.
Ferroptosis has emerged as a critical mechanism in the development and progression of various tumors, particularly diffuse large B-cell lymphoma (DLBCL). However, the thorough characterization of ferroptosis-related genes in DLBCL remains inadequately explored. We retrieved datasets associated with DLBCL and ferroptosis gene sets from the Gene Expression Omnibus (GEO) database and the Ferroptosis Database (FerrDb), resulting in the identification of 27 differentially expressed ferroptosis-related genes (DE-FRGs) linked to DLBCL. Utilizing the LASSO and Support Vector Machine Recursive Feature Elimination (SVW-RFE) algorithms, we identified 10 genes-MT1G, MTOR, BRD4, ACO1, SAT1, PEBP1, LPIN1, ATM, SRXN1, and PRDX1-as key biomarker candidates with significant diagnostic potential. Functional enrichment analyses revealed that these biomarker genes are likely involved in regulating several critical biological pathways implicated in DLBCL pathogenesis, including immune response, oxidative phosphorylation, and cell cycle regulation. Moreover, we identified 246 potential therapeutic agents targeting these 10 biomarker genes. Concurrently, competitive endogenous RNA (ceRNA) network analysis uncovered a complex regulatory network centered on the identified biomarker genes. Additionally, CIBERSORT analysis highlighted notable alterations in the immune microenvironment of DLBCL patients. We propose a diagnostic strategy that provides novel insights into the molecular mechanisms underlying DLBCL. Nevertheless, further validation of the practical value of this strategy for DLBCL diagnosis is necessary before its clinical application.
铁死亡已成为各种肿瘤发生发展的关键机制，尤其是弥漫性大B细胞淋巴瘤（DLBCL）。然而，DLBCL中铁死亡相关基因的全面特征仍未得到充分探索。我们从基因表达综合数据库（GEO）和铁死亡数据库（FerrDb）中检索了与DLBCL和铁死亡基因集相关的数据集，从而鉴定出27个与DLBCL相关的差异表达铁死亡相关基因（DE-FRGs）。利用套索回归和支持向量机递归特征消除（SVW-RFE）算法，我们确定了10个基因——MT1G、MTOR、BRD4、ACO1、SAT1、PEBP1、LPIN1、ATM、SRXN1和PRDX1——作为具有显著诊断潜力的关键生物标志物候选基因。功能富集分析表明，这些生物标志物基因可能参与调节DLBCL发病机制中涉及的几个关键生物学途径，包括免疫反应、氧化磷酸化和细胞周期调控。此外，我们确定了246种靶向这10个生物标志物基因的潜在治疗药物。同时，竞争性内源RNA（ceRNA）网络分析揭示了一个以鉴定出的生物标志物基因为中心的复杂调控网络。此外，CIBERSORT分析突出了DLBCL患者免疫微环境的显著变化。我们提出了一种诊断策略，为DLBCL的分子机制提供了新的见解。然而，在临床应用之前，有必要进一步验证该策略对DLBCL诊断的实际价值。
