A glycolysis-based ten-gene signature correlates with the clinical outcome, molecular subtype and IDH1 mutation in glioblastoma

Chen, Cong; Shi, Yu; Li, Yong; He, Zhicheng; Zhou, Kai; Zhang, Xiaoning; Yang, Kai‐Di; Wu, Jinrong; Kung, Hsiang‐Fu; Ping, Yi‐Fang; Bian, Xiu‐Wu

doi:10.1016/j.jgg.2017.05.007

Cited by 38 publications

(38 citation statements)

References 68 publications

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“…Gene sets of (c) Hallmark, (d) KEGG, (e) Reactome, (f) BioCarta and (g) PID associated with 4-mRNA signature based risk score were performed by GSEA with nominal P-value < 0.05, FDR < 0.1 and |NES| > 1. 6 to mesenchymal subtype and mutation of IDH1 in glioblastoma [24]. Consistent with those studies, we found that a glycolysis signature composed of four glycolytic genes (NUP205, NUPL2, PFKFB1 and PKM) can predict the survival of patients with bladder cancer accurately in the TCGA cohort as well as in two independent GEO cohorts, suggesting its favorable performance for prediction.…”

Section: Discussionsupporting

confidence: 89%

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

Zhang

Gou

et al. 2020

Cancer Cell Int

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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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Section: Discussionsupporting

confidence: 89%

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

Zhang

Gou

et al. 2020

Cancer Cell Int

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“…Several research studies have focused on the systematic analysis of glycolysis and tumors, including glioblastoma (15), liver cancer (16), and endometrial cancer (17). However, comprehensive analysis of the interrelation between glycolysis, immune infiltration, and clinical prognosis in GC patients is lacking.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Seven-Gene Signature Based on Glycolysis Is Closely Related to the Prognosis and Tumor Immune Infiltration of Patients With Gastric Cancer

Cai

et al. 2020

Front. Oncol.

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Background: Gastric cancer (GC) is one of the most common malignancies worldwide, exhibiting a high morbidity, and mortality. As the various treatment methods for gastric cancer are limited by disadvantages, many efforts to improve the efficacy of these treatments are being taken. Metabolic recombination is an important characteristic of cancer and has gradually caused a recent upsurge in research. However, systematic analysis of the interaction between glycolysis and GC patient prognosis and its potential associations with immune infiltration is lacking but urgently needed. Methods: We obtained the gene expression data and clinical materials of GC derived from The Cancer Genome Atlas (TCGA) dataset. Univariate and multivariate Cox proportional regression analyses were performed to select the optimal prognosis-related genes for subsequent modeling. We then validated our data in the GEO database and further verified the gene expression using the Oncomine database and PCR experiments. Besides, Gene set variation analysis (GSVA) analysis was employed to further explore the differences in activation status of biological pathways between the high and low risk groups. Furthermore, a nomogram was adopted to predict the individualized survival rate of GC patients. Finally, a violin plot and a TIMMER analysis were performed to analyse the characteristics of immune infiltration in the microenvironment. Results: A seven-gene signature, including STC1, CLDN9, EFNA3, ZBTB7A, NT5E, NUP50, and CXCR4, was established. Based on this seven-gene signature, the patients in the training set and testing sets could be divided into high-risk and low-risk groups. In addition, a nomogram based on risk and age showed good calibration and moderate discrimination. The results proved that the seven-gene signature had a strong capacity to predict the GC patient prognosis. Collectively, the violin plot and TIMMER analysis demonstrated that an immunosuppressive tumor microenvironment caused by hyperglycolysis led to poor prognosis. Yu et al. Seven-Gene Signature in GC Conclusion: Taken together, these results established a genetic signature for gastric cancer based on glycolysis, which has reference significance for the in-depth study of the metabolic mechanism of gastric cancer and the exploration of new clinical treatment strategies.

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“…A nine-gene signature associated with cellular glycolysis was a potent indicator for the prediction of overall survival in patients with endometrial cancer [23]. The glycolysis score represented by expression of ten glycolytic genes predicted unfavorable clinical outcome for patients with glioblastoma and was closely related to mesenchymal subtype and mutation of IDH1 in glioblastoma [24]. Consistent with those studies, we found that a glycolysis signature composed of four glycolytic genes (NUP205, NUPL2, PFKFB1 and PKM) can predict the survival of patients with bladder cancer accurately in the TCGA cohort as well as in two independent GEO cohorts, suggesting its favorable performance for prediction.…”

Section: Discussionmentioning

confidence: 99%

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

Zhang

Gou

et al. 2020

Preprint

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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.

show abstract

A glycolysis-based ten-gene signature correlates with the clinical outcome, molecular subtype and IDH1 mutation in glioblastoma

Cited by 38 publications

References 68 publications

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

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

RETRACTED: Seven-Gene Signature Based on Glycolysis Is Closely Related to the Prognosis and Tumor Immune Infiltration of Patients With Gastric Cancer

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

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