肿瘤细胞治疗研究
英文原题：CD70 is a potential prognostic marker and significantly regulates cellular function in diffuse large B-cell lymphoma.
本研究提示 CD70 是 DLBCL 潜在的诊断与治疗生物标志物。
大量研究表明，共刺激分子表达失调在癌症生物学中发挥关键作用。然而，弥漫大 B 细胞淋巴瘤（DLBCL）中肿瘤内 CD70 对疾病起始、进展和免疫应答的影响尚不清楚。本研究旨在阐明 CD70 在 DLBCL 诊断和预后中的临床意义及其与免疫微环境的关系。我们首先利用多个在线数据库（TIMER、GEPIA、GENT2、TNMPlot、GSCA 和 GEO）分析包括 DLBCL 在内的多种癌症中 CD70 表达；随后评估 CD70 与 DLBCL 临床特征及预后的关联，并研究其在 DLBCL 细胞中的功能。使用 cBioPortal 分析 CD70 基因组改变，通过共表达网络分析评估 CD70 相关生物学功能，并利用 TIMER2.0 检验 CD70 表达与免疫细胞浸润的相关性。结果显示，与配对正常组织相比，DLBCL 组织中 CD70 表达显著上调；CD70 高表达与患者临床结局较差相关。体外实验表明，抑制 CD70 可促进 DLBCL 细胞凋亡并诱导 G1 期阻滞。基因组改变分析显示，CD70 改变患者的总生存期差于未改变患者。共表达和功能富集分析提示 CD70 与肿瘤坏死因子受体结合及 NF-κB 信号通路功能相关。此外，DLBCL 中 CD70 表达水平与 B 细胞和 NK 细胞浸润呈负相关。总之，本研究提示 CD70 是 DLBCL 潜在诊断和治疗生物标志物，并为开发靶向 CD70 的 DLBCL 新疗法提供了有价值的见解。
Extensive research has demonstrated that dysregulation of costimulatory molecule expression plays a pivotal role in cancer biology. However, the impact of intratumoral CD70 on the initiation, progression, and immune response in diffuse large B-cell lymphoma (DLBCL) remains poorly understood. This study aims to elucidate the clinical significance of CD70 in DLBCL diagnosis and prognosis, as well as its relationship with the immune microenvironment. We first analyzed CD70 expression across various cancers, including DLBCL, using multiple online databases (TIMER, GEPIA, GENT2, TNMPlot, GSCA, and GEO). We then evaluated the clinical correlations and prognostic value of CD70 in DLBCL. Additionally, we investigated the functional role of CD70 in DLBCL cells. Genomic alterations of CD70 were analyzed using the cBioPortal online tool. Co-expression network analysis was performed to assess the biological functions associated with CD70. Furthermore, we utilized TIMER2.0 to examine the correlation between CD70 expression and immune cell infiltration. Our results revealed that CD70 expression was significantly upregulated in DLBCL tissues compared to matched normal tissues, and high CD70 expression was associated with poor clinical outcomes in DLBCL patients. In vitro experiments demonstrated that CD70 inhibition promotes apoptosis and induces G1 phase arrest in DLBCL cells. Genomic alteration analysis showed that patients with CD70 alterations exhibited worse overall survival compared to those without such alterations. Co-expression and functional enrichment analyses indicated that CD70 is functionally related to tumor necrosis factor receptor binding and the NF- B signaling pathway. Moreover, we found that CD70 expression levels were negatively correlated with B cell and NK cell infiltration in DLBCL. In conclusion, this study suggests that CD70 is a potential diagnostic and therapeutic biomarker for DLBCL. Our findings provide valuable insights for the development of novel therapeutic strategies targeting CD70 in DLBCL treatment.
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