A glycolysis-based 4-mRNA signature correlates with the prognosis and cell cycle process in patients with bladder cancer

Abstract

Background: Bladder cancer is one of the most prevalent malignancies worldwide. However, traditional indicators have limited predictive effects on the clinical outcomes of bladder cancer. The aim of this study was to develop and validate a glycolysis-related gene signature for predicting the prognosis of patients with bladder cancer that have limited therapeutic options. Methods: mRNA expression profiling was obtained from patients with bladder cancer from The Cancer Genome Atlas (TCGA) database. Gene set enrichment analysis (GSEA) was conducted to identify glycolytic gene sets that were significantly different between bladder cancer tissues and paired normal tissues. A prognosis-related gene signature was constructed by univariate and multivariate Cox analysis. Kaplan-Meier curves and time-dependent receiver operating characteristic (ROC) curves were utilized to evaluate the signature. A nomogram combined with the gene signature and clinical parameters was constructed. Correlations between glycolysis-related gene signature and molecular characterization as well as cancer subtypes were analyzed. RT-qPCR was applied to analyze gene expression. Functional experiments were performed to determine the role of PKM2 in the proliferation of bladder cancer cells. Results: Using a Cox proportional regression model, we established that a 4-mRNA signature (NUP205, NUPL2, PFKFB1 and PKM) was significantly associated with prognosis in bladder cancer patients. Based on the signature, patients were split into high and low risk groups, with different prognostic outcomes. The gene signature was an independent prognostic indicator for overall survival. The ability of the 4-mRNA signature to make an accurate prognosis was tested in two other validation datasets. GSEA was performed to explore the 4-mRNA related canonical pathways and biological processes, such as the cell cycle, hypoxia, p53 pathway, and PI3K/AKT/mTOR pathway. A heatmap showing the correlation between risk score and cell cycle signature was generated. RT-qPCR revealed the genes that were differentially expressed between normal and cancer tissues. Experiments showed that PKM2 plays essential roles in cell proliferation and the cell cycle. Conclusion: The established 4-mRNA signature may act as a promising model for generating accurate prognoses for patients with bladder cancer, but the specific biological mechanism needs further verification.

An epithelial–mesenchymal transition-related long noncoding RNA signature correlates with the prognosis and progression in patients with bladder cancer

“…The nomogram can be used to diagnose or predict the onset or progression of a disease [ 13 ]. We established a nomogram according to the risk score and other clinicopathological parameters including age, gender, AJCC stage, T stage, and N stage ( Figure 5 A).…”

The effect of a novel glycolysis-related gene signature on progression, prognosis and immune microenvironment of renal cell carcinoma

“…However, the predictive ability of single-gene biomarkers is limited in RCC prognosis analysis and multiple-genes signature maybe a better strategy [ 16 ]. So far, only four studies have established the glycolytic risk signature in lung adenocarcinoma [ 17 ], endometrial cancer [ 16 ], hepatocellular carcinoma [ 18 ] and bladder cancer [ 19 ]. Therefore, to explore the potential roles of glycolytic metabolism and glycolysis-related genes in RCC, a series of bioinformatic analyses were performed through TCGA database (609 samples).…”

Correlations between glycolysis with clinical traits and immune function in bladder urothelial carcinoma

“…Previous studies have come to consistent conclusions. Using a glycolysis-based 4-mRNA signature, they found that high-risk group had higher mortality and poorer OS than low-risk group in bladder cancer [ 10 ]. It was generally held that glycolysis was related to poor prognosis in cancers, and the reliability of glycolysis score was demonstrated in another way.…”

“…Moreover, another enzyme, PKM2, plays an essential role in cell proliferation and cell cycle. The down-regulation of PKM2 suppressed proliferation of bladder cancer cells, with a decreased proportion of cells in the DNA synthesis phase [ 10 ]. Glycolysis plays a critical role in bladder cancer.…”