Tang Jing, Lu Bo, Bin Ting, Xu Xiao-Jun, Lin Chao, Wang Ying, Xie Wen-Lin
Department of Haematology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China.
Pediatric Hematology Laboratory, Division of Hematology/Oncology, Department of Pediatrics, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China.
Ann Med. 2024 Dec;56(1):2425065. doi: 10.1080/07853890.2024.2425065. Epub 2024 Dec 3.
Diffuse large B-cell lymphoma (DLBCL), the most prevalent type of non-Hodgkin's lymphoma, exhibits significant correlations with efferocytosis-related molecules (ERMs) concerning invasion, metastasis, and clinical outcomes. This study aims to establish an efferocytosis-related gene signature specifically linked to DLBCL.
Key module genes linked to DLBCL were identified via weighted gene co-expression network analysis (WGCNA) in GSE32018. Univariate Cox analysis of GSE31312 revealed ERMs associated with DLBCL survival. Differential expression analysis identified differentially expressed genes (DEGs) between DLBCL subtypes and normal samples. Venn diagram analysis identified common DEGs and key module genes. A DLBCL gene signature was built by using univariate Cox and least absolute shrinkage and selection operator (LASSO) analysis. Gene functional enrichment, immune microenvironment, and immunotherapy analyses compared two risk subgroups. Prognostic gene expression was validated at the single-cell level.
In the GSE32018 dataset, 1760 key module genes related to DLBCL were identified. Using GSE31312, 14 ERMs associated with DLBCL prognosis were determined.Then, an ERMs-related prognostic signature, including small nuclear ribonucleoprotein polypeptides B (SNRPB) and centrosomal protein 290 (CEP290), was established. Independent prognostic analysis showed that the RiskScore derived from this signature was a prognostic factor. Significant immune microenvironment differences were observed between two risk subgroups. Additionally, chemotherapeutic drug sensitivity results indicated the signature could predict therapeutic response. Eventually, expression of SNRPB and CEP290 was confirmed in B cells.
The prognostic signature comprised of SNRPB and CEP290 based on ERMs-DEGs was established, providing a theoretical basis and reference value for DLBCL research.
弥漫性大B细胞淋巴瘤(DLBCL)是最常见的非霍奇金淋巴瘤类型,在侵袭、转移和临床结局方面与胞葬作用相关分子(ERM)存在显著相关性。本研究旨在建立一个与DLBCL特异性相关的胞葬作用相关基因特征。
通过加权基因共表达网络分析(WGCNA)在GSE32018中鉴定与DLBCL相关的关键模块基因。对GSE31312进行单变量Cox分析,揭示与DLBCL生存相关的ERM。差异表达分析确定了DLBCL亚型与正常样本之间的差异表达基因(DEG)。维恩图分析确定了共同的DEG和关键模块基因。通过单变量Cox和最小绝对收缩和选择算子(LASSO)分析构建了DLBCL基因特征。基因功能富集、免疫微环境和免疫治疗分析比较了两个风险亚组。在单细胞水平验证了预后基因表达。
在GSE32018数据集中,鉴定出1760个与DLBCL相关的关键模块基因。利用GSE31312,确定了14个与DLBCL预后相关的ERM。然后,建立了一个与ERM相关的预后特征,包括小核核糖核蛋白多肽B(SNRPB)和中心体蛋白290(CEP290)。独立预后分析表明,从该特征得出的风险评分是一个预后因素。在两个风险亚组之间观察到显著的免疫微环境差异。此外,化疗药物敏感性结果表明该特征可以预测治疗反应。最终,在B细胞中证实了SNRPB和CEP290的表达。
基于ERM-DEG建立了由SNRPB和CEP290组成的预后特征,为DLBCL研究提供了理论依据和参考价值。