Abstract
BackgroundUrothelial 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.MethodsONCOMINE, 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.ResultsThe 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).ConclusionsThis 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.
Highlights
Urothelial bladder cancer (BC) is one of the most prevalent malignancies with high mortality and high recurrence rate
Significantly increased CCL13 (P = 0.011, Fold change = 2.654) were observed in BC compared with normal tissue
Similar results were found when we assessed the transcriptional levels of CC chemokines using the Gene Expression Profiling Interactive Analysis (GEPIA) database, CCL2, CCL14, CCL21 and CCL23 were lower in BC patients than normal patients (Fig. 2)
Summary
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. We know little about the function of distinct CC chemokines in BC. Sequencing and gene expression studies have found the CC chemokines may play an important role in the tumorigenesis and progression of distinct tumors [11,12,13]. Previous studies have identified several CC chemokines were associated with disease-specific survival [14], tumor growth and progression [12]. CC chemokines have multiple functions in tumor progression and invasion, and they serve as prognostic biomarkers for many types of tumors, including BC. The expression and prognostic values of CC chemokines in BC still remain unclear
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