Fujian Institute of Hematology, Fujian Medical Center of Hematology, Fujian Provincial Key Laboratory on Hematology; Fujian Medical University Union Hospital, Fuzhou, China.
Meng Chao Hepatobiliary Hospital Affiliated to Fujian Medical University, Fuzhou, China.
BMC Cancer. 2021 Aug 17;21(1):927. doi: 10.1186/s12885-021-08660-4.
Diffuse large B-cell lymphoma is the most common form of non-Hodgkin lymphoma globally, and patients with relapsed or refractory DLBCL typically experience poor long-term outcomes.
Differentially expressed genes associated with DLBCL were identified using two GEO datasets in an effort to detect novel diagnostic or prognostic biomarkers of this cancer type, after which receiver operating characteristic curve analyses were conducted. Genes associated with DLBCL patient prognosis were additionally identified via WCGNA analyses of the TCGA database. The expression of PLA2G7 in DLBCL patient clinical samples was further assessed, and the functional role of this gene in DLBCL was assessed through in vitro and bioinformatics analyses.
DLBCL-related DEGs were found to be most closely associated with immune responses, cell proliferation, and angiogenesis. WCGNA analyses revealed that PLA2G7 exhibited prognostic value in DLBCL patients, and the upregulation of this gene in DLBCL patient samples was subsequently validated. PLA2G7 was also found to be closely linked to tumor microenvironmental composition such that DLBCL patients expressing higher levels of this gene exhibited high local monocyte and gamma delta T cell levels. In vitro experiments also revealed that knocking down PLA2G7 expression was sufficient to impair the migration and proliferation of DLBCL cells while promoting their apoptotic death. Furthmore, the specific inhibitor of PLA2G7, darapladib, could noticeably restrained the DLBCL cell viability and induced apoptosis.
PLA2G7 may represent an important diagnostic, prognostic, or therapeutic biomarker in patients with DLBCL.
弥漫性大 B 细胞淋巴瘤（DLBCL）是全球最常见的非霍奇金淋巴瘤，复发或难治性 DLBCL 患者通常预后较差。
我们使用两个 GEO 数据集鉴定与 DLBCL 相关的差异表达基因，以试图发现这种癌症类型的新的诊断或预后生物标志物，随后进行了接收者操作特征曲线分析。通过 TCGA 数据库的 WGCNA 分析，进一步确定了与 DLBCL 患者预后相关的基因。此外，我们还评估了 PLA2G7 在 DLBCL 患者临床样本中的表达，并通过体外和生物信息学分析评估了该基因在 DLBCL 中的功能作用。
与 DLBCL 相关的 DEGs 与免疫反应、细胞增殖和血管生成最为密切相关。WGCNA 分析显示 PLA2G7 在 DLBCL 患者中具有预后价值，随后验证了该基因在 DLBCL 患者样本中的上调。PLA2G7 还与肿瘤微环境组成密切相关，即表达该基因水平较高的 DLBCL 患者具有较高的局部单核细胞和γδT 细胞水平。体外实验还表明，敲低 PLA2G7 的表达足以损害 DLBCL 细胞的迁移和增殖，同时促进其凋亡。此外，PLA2G7 的特异性抑制剂达拉普利（darapladib）可明显抑制 DLBCL 细胞活力并诱导其凋亡。
PLA2G7 可能是 DLBCL 患者重要的诊断、预后或治疗生物标志物。
