Department of Geriatric Urology, Xiangya International Medical Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People's Republic of China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People's Republic of China.
BMC Urol. 2021 Dec 10;21(1):173. doi: 10.1186/s12894-021-00938-w.
Urothelial bladder cancer (BC) is one of the most prevalent malignancies with high mortality and high recurrence rate. Angiogenesis, tumor growth and metastasis of multiple cancers are partly modulated by CC chemokines. However, we know little about the function of distinct CC chemokines in BC.
ONCOMINE, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier plotter, cBioPortal, GeneMANIA, and TIMER were used for analyzing differential expression, prognostic value, protein-protein interaction, genetic alteration and immune cell infiltration of CC chemokines in BC patients based on bioinformatics.
The results showed that transcriptional levels of CCL2/3/4/5/14/19/21/23 in BC patients were significantly reduced. A significant relation was observed between the expression of CCL2/11/14/18/19/21/23/24/26 and the pathological stage of BC patients. BC patients with high expression levels of CCL1, CCL2, CCL3, CCL4, CCL5, CCL8, CCL13, CCL15, CCL17, CCL18, CCL19, CCL22, CCL25, CCL27 were associated with a significantly better prognosis. Moreover, we found that differentially expressed CC chemokines are primarily correlated with cytokine activity, chemokines receptor binding, chemotaxis, immune cell migration. Further, there were significant correlations among the expression of CC chemokines and the infiltration of several types of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells).
This study is an analysis to the potential role of CC chemokines in the therapeutic targets and prognostic biomarkers of BC, which gives a novel insight into the relationship between CC chemokines and BC.
膀胱癌(BC)是最常见的恶性肿瘤之一,死亡率和复发率都很高。趋化因子 C 家族(CC 家族)中的趋化因子在多种癌症的血管生成、肿瘤生长和转移中起部分调节作用。然而,我们对 CC 家族趋化因子在 BC 中的功能知之甚少。
基于生物信息学,使用 ONCOMINE、基因表达谱分析交互工具(GEPIA)、Kaplan-Meier plotter、cBioPortal、GeneMANIA 和 TIMER 分析 CC 家族趋化因子在 BC 患者中的差异表达、预后价值、蛋白-蛋白相互作用、遗传改变和免疫细胞浸润。
结果显示,BC 患者的 CCL2/3/4/5/14/19/21/23 的转录水平显著降低。CCL2/11/14/18/19/21/23/24/26 的表达与 BC 患者的病理分期呈显著相关。CCL1、CCL2、CCL3、CCL4、CCL5、CCL8、CCL13、CCL15、CCL17、CCL18、CCL19、CCL22、CCL25、CCL27 表达水平较高的 BC 患者预后显著改善。此外,我们发现差异表达的 CC 趋化因子主要与细胞因子活性、趋化因子受体结合、趋化作用、免疫细胞迁移相关。进一步的,CC 趋化因子的表达与几种类型免疫细胞(B 细胞、CD8+T 细胞、CD4+T 细胞、巨噬细胞、中性粒细胞和树突状细胞)的浸润存在显著相关性。
本研究分析了 CC 趋化因子在 BC 治疗靶点和预后生物标志物中的潜在作用,为 CC 趋化因子与 BC 之间的关系提供了新的见解。