Identification and prognostic value of a glycolysis-related gene signature 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.

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A Novel Ferroptosis-related Gene Signature for Overall Survival Prediction in Patients with Bladder cancer

10.21203/rs.3.rs-333257/v1 ◽

2021 ◽

Author(s):

Liyuan Wu ◽

Feiya Yang ◽

Nianzeng Xing

Keyword(s):

Overall Survival ◽

Bladder Cancer ◽

Cox Regression ◽

Risk Group ◽

Risk Groups ◽

Gene Signature ◽

Survival Prediction ◽

Related Gene ◽

Cox Regression Analysis ◽

Prognostic Prediction

Abstract Background Bladder cancer (BC) is a highly heterogeneous disease, which makes the prognostic prediction challenging. Ferroptosis is related to a variety of biological pathways, including those involved in the metabolism of amino acids, lipids, and iron. However, the prognostic value of ferroptosis-related genes in BC remains to be further elucidated. Methods In this study, the mRNA expression profiles and corresponding clinical data of BC patients were downloaded from public databases. The least absolute shrinkage and selection operator (LASSO) Cox regression model was utilized to construct a multigene signature and validated it. Results Our results showed 12 differentially expressed genes (DEGs) were correlated with overall survival (OS) in the univariate Cox regression analysis (all adjusted P< 0.05). A 9-gene signature was constructed to stratify patients into two risk groups. Patients in the high-risk group showed significantly reduced OS compared with patients in the low-risk group (P < 0.001). The risk score was an independent predictor for OS in multivariate Cox regression analyses (HR> 1, P< 0.01). Receiver operating characteristic (ROC) curve analysis confirmed the signature's predictive capacity. Functional analysis revealed that immune-related pathways were enriched, and immune status were different between two risk groups, especially in humoral immune response process. Conclusion In conclusion, a novel ferroptosis-related gene signature can be used for prognostic prediction in BC. Targeting ferroptosis may be a therapeutic alternative for BC.

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Prognostic value of hypoxia gene expression in bladder cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.548 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 548-548

Author(s):

Hyun Chang ◽

Seung-Hyun Lee ◽

Taeryool Koo ◽

Moon Ho Kim ◽

Soo-Yoon Sung

Keyword(s):

Bladder Cancer ◽

Urothelial Carcinoma ◽

Cancer Patients ◽

Prognostic Value ◽

Cox Regression ◽

Gene Signature ◽

Survival Curves ◽

Kaplan Meier ◽

Bladder Urothelial Carcinoma

548 Background: The prognostic value of hypoxia in bladder cancer remains unknown. We aimed to evaluate the potential role of hypoxia gene signature as prognostic factors in bladder cancer patients. Methods: We investigated the hypoxia gene signature and clinicopathologic features of The Cancer Genome Atlas (TCGA) bladder urothelial carcinoma (n = 408) using the Kaplan-Meier survival curves and multivariate Cox regression analyses. The clinicopathologic data and the processed data of hypoxia gene signature were obtained from TCGA Bladder urothelial carcinoma database. Results: Hypoxia gene signature score was significantly associated with overall survival (OS) and progression-free survival (PFS). Higher score resulted in shorter OS and PFS in Kaplan-Meier survival curves with Log-rank test ( P < 0.01 and P <0.05, respectively). In multivariate analysis containing clinical prognostic variables, higher hypoxia gene signature score predicted poor OS (adjusted HR= 1.58, 95% CI 1.15 - 2.19; P <0.01). Conclusions: Hypoxia gene signature was an independent prognostic factor in bladder cancer. Prospective studies are needed to evaluate the prognostic role of hypoxia in bladder cancer patients.

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