Abstract
BackgroundBladder cancer (BC) is a commonly diagnosed malignant tumor in the urinary system, with a high morbidity and a high recurrence rate. Current studies indicated that metabolism-associated genes (MAGs) having critical roles in the etiology of BC. The present study aims to identify differentially expressed MAGs and construct a MAGs based prognostic risk signature for BC by using The Cancer Genome Atlas (TCGA) database and proteomics data.MethodsRNA-sequence data from the TCGA database and proteomics data from our BC samples were used to identify differentially expressed MAGs and construct a MAGs based prognostic signature in BC. Subsequently, survival analysis and nomogram were used to evaluate the prognostic and predictive value of the MAGs based signature in BC. RNA isolation and reverse transcription‑quantitative PCR (RT-qPCR) were further performed to investigate the expression levels of MAGs in BC cells and explore the relationship between MAGs and M2 tumor associated macrophages (TAMs) secreted transforming growth factor-β1 (TGF-β1) in BC cells.ResultsA total of 23 differentially expressed MAGs were identified and five MAGs were finally used to construct a MAGs based signature. Survival analysis revealed that the MAGs based signature was closely correlated with the survival outcomes of patients with BC. A nomogram with the MAGs based signature risk score and clinical features was also constructed to facilitate the individualized prediction of BC patients. RT-qPCR showed that five MAGs were significantly differentially expressed and the expression levels of three MAGs were positively correlated with M2 TAMs secreted TGF-β1 in T24 cells.ConclusionsOur study identified novel prognostic MAGs and constructed a MAGs based signature, which can be used as an independent factor in evaluating the prognosis of patients with BC. Furthermore, M2 TAMs may promote the expression of MAGs via the TGF-β1 signaling pathway in the microenvironment of BC. Further clinical trials and experimental explorations are needed to validate our observations in BC.
Highlights
Bladder cancer (BC) is a commonly diagnosed malignant tumor in the urinary system, with a high morbidity and a high recurrence rate
A protein–protein interaction (PPI) network of 23 metabolism-associated genes (MAGs) was retrieved from the STRING database and their correlations were further screened in Cytoscape
We found that the most significant Gene ontology (GO) enriched terms involved in metabolism were amino acid metabolic process, antibiotic metabolic process, organic hydroxy compound catabolic process, alcohol metabolic process, and glycogen catabolic process (BP, biological process); myelin sheath and mitochondrial matrix (CC, cellular component); and lyase activity, oxidoreductase activity cofactor binding, coenzyme binding electron transfer activity, and NAD binding (MF, molecular function) (Fig. 2a)
Summary
Bladder cancer (BC) is a commonly diagnosed malignant tumor in the urinary system, with a high morbidity and a high recurrence rate. Especially metabolism associated genes (MAGs), has gained great value, power, and importance for cancer research, as potential biomarkers in early diagnosis, and as valuable factors for the discovery of novel mechanisms controlling tumorigenesis, paving the way to new treatment strategies and therapies [11,12,13]. The effect of the metabolism on the progression of the tumor has recently emerged as a new field in BC research. Several metabolites such as taurine, carnitine, and cholinergic compounds have been proposed as biomarkers for BC in urine [14,15,16]. Potential reliable and valuable MAGs to early prediction, progression, and the management of BC still limited, and it needs to be further expanded
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