Glycolysis‐Related Genes Serve as Potential Prognostic Biomarkers in Clear Cell Renal Cell Carcinoma

Zhang, Yan; Chen, Mingying; Liu, Meihong; Xu, Yingkun; Wu, Guangzhen

doi:10.1155/2021/6699808

Cited by 42 publications

(32 citation statements)

References 55 publications

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“…2OGDH is decreased in CKD induced by high-salt diet and aristocholic acid administration [ 22 , 115 ], as has been reported in non-diabetic CKD patients [ 42 ]. On the other hand, in RCC 2OGDH lower expression was associated with poor outcome [ 116 ]. Together, this indicates a decreased synthesis of succinyl-CoA in some progressive kidney diseases.…”

Section: Succinyl-coamentioning

confidence: 99%

Involvement of Tricarboxylic Acid Cycle Metabolites in Kidney Diseases

et al. 2021

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Mitochondria are complex organelles that orchestrate several functions in the cell. The primary function recognized is energy production; however, other functions involve the communication with the rest of the cell through reactive oxygen species (ROS), calcium influx, mitochondrial DNA (mtDNA), adenosine triphosphate (ATP) levels, cytochrome c release, and also through tricarboxylic acid (TCA) metabolites. Kidney function highly depends on mitochondria; hence mitochondrial dysfunction is associated with kidney diseases. In addition to oxidative phosphorylation impairment, other mitochondrial abnormalities have been described in kidney diseases, such as induction of mitophagy, intrinsic pathway of apoptosis, and releasing molecules to communicate to the rest of the cell. The TCA cycle is a metabolic pathway whose primary function is to generate electrons to feed the electron transport system (ETS) to drives energy production. However, TCA cycle metabolites can also release from mitochondria or produced in the cytosol to exert different functions and modify cell behavior. Here we review the involvement of some of the functions of TCA metabolites in kidney diseases.

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Section: Succinyl-coamentioning

confidence: 99%

Involvement of Tricarboxylic Acid Cycle Metabolites in Kidney Diseases

et al. 2021

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“…Glucose-6-phosphate dehydrogenase (G6PD) serves as a pacemaker of PPP due to its activity to shunt glucose flux to PPP and catalyze the first and rate-limiting step of PPP (17). Mounting evidence indicated that increased glucose flux towards PPP and overactivation of G6PD are common in many cancer types, including clear cell renal cell carcinoma, hepatocellular carcinoma, colorectal cancer, prostate cancer, and ESCC (23)(24)(25)(26)(27). It is known that G6PD overactivation in tumor cells is regulated at the transcriptional or posttranslational level (17,21,22,(27)(28)(29).…”

Section: Introductionmentioning

confidence: 99%

DNA Polymerase Iota Promotes Esophageal Squamous Cell Carcinoma Proliferation Through Erk-OGT-Induced G6PD Overactivation

Gao

et al. 2021

Front. Oncol.

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Esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers with rapid progression and a high mortality rate. Our previous study demonstrated that DNA polymerase iota (Pol ι) is overexpressed in ESCC tumors and correlates with poor prognosis. However, its role in ESCC proliferation remains obscure. We report here that Pol ι promotes ESCC proliferation and progression through Erk- O-GlcNAc transferase (OGT) regulated Glucose-6-phosphate dehydrogenase (G6PD) overactivation. Cell clonogenic ability was assessed by colony formation assay. Cell proliferation was assessed by EdU incorporation assay. Our transcriptome data was reanalyzed by GSEA and validated by analysis of cellular metabolism, G6PD activity, and cellular NADPH concentration. The level of Pol ι, OGT, G6PD and O-GlcNAcylation in ESCC cells and patient samples were analyzed. The MEK inhibitor PD98059 was applied to confirm OGT expression regulation by the Erk signaling. The G6PD inhibitor polydatin was used to examine the role of G6PD activation in Pol ι promoted proliferation. We found that Pol ι promotes ESCC proliferation. It shunted the glucose flux towards the pentose phosphate pathway (PPP) by activating G6PD through OGT-promoted O-GlcNAcylation. The expression of OGT was positively correlated with Pol ι expression and O-GlcNAcylation. Notably, elevated O-GlcNAcylation was correlated with poor prognosis in ESCC patients. Pol ι was shown to stimulate Erk signaling to enhance OGT expression, and the G6PD inhibitor polydatin attenuated Pol ι induced tumor growth in vitro and in vivo. In conclusion, Pol ι activates G6PD through Erk-OGT-induced O-GlcNAcylation to promote the proliferation and progression of ESCC, supporting the notion that Pol ι is a potential biomarker and therapeutic target of ESCC.

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“…A previous study demonstrated that NUP43 plays the role of promoter in the progression of tumors [ 43 ]. Yan Zhang et al developed glycolysis-related genes to predict the outcomes of patients in clear cell renal cell carcinoma (ccRCC); PGK1 is one of these genes, whose high expression predicted poor prognosis in patients with ccRCC [ 44 ]. PGK1 expression was also significantly increased in BC tissues and associated with HER2+ and positive status of ER [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel glycolysis-related signature to predict the prognosis of patients with breast cancer

Deng

et al. 2021

World J Surg Onc

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Background Breast cancer (BC) has a high incidence and mortality rate in females. Its conventional clinical characteristics are far from accurate for the prediction of individual outcomes. Therefore, we aimed to develop a novel signature to predict the survival of patients with BC. Methods We analyzed the data of a training cohort from the Cancer Genome Atlas (TCGA) database and a validation cohort from the Gene Expression Omnibus (GEO) database. After the applications of Gene Set Enrichment Analysis (GSEA) and Cox regression analyses, a glycolysis-related signature for predicting the survival of patients with BC was developed; the signature contained AK3, CACNA1H, IL13RA1, NUP43, PGK1, and SDC1. Furthermore, on the basis of expression levels of the six-gene signature, we constructed a risk score formula to classify the patients into high- and low-risk groups. The receiver operating characteristic (ROC) curve and the Kaplan-Meier curve were used to assess the predicted capacity of the model. Later, a nomogram was developed to predict the outcomes of patients with risk score and clinical features over a period of 1, 3, and 5 years. We further used Human Protein Atlas (HPA) database to validate the expressions of the six biomarkers in tumor and sample tissues, which were taken as control. Results We constructed a six-gene signature to predict the outcomes of patients with BC. The patients in the high-risk group showed poor prognosis than those in the low-risk group. The area under the curve (AUC) values were 0.719 and 0.702, showing that the prediction performance of the signature is acceptable. Additionally, Cox regression analysis revealed that these biomarkers could independently predict the prognosis of BC patients with BC without being affected by clinical factors. The expression levels of all six biomarkers in BC tissues were higher than that in normal tissues; however, AK3 was an exception. Conclusion We developed a six-gene signature to predict the prognosis of patients with BC. Our signature has been proved to have the ability to make an accurate prediction and might be useful in expanding the hypothesis in clinical research.

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Glycolysis‐Related Genes Serve as Potential Prognostic Biomarkers in Clear Cell Renal Cell Carcinoma

Cited by 42 publications

References 55 publications

Involvement of Tricarboxylic Acid Cycle Metabolites in Kidney Diseases

Involvement of Tricarboxylic Acid Cycle Metabolites in Kidney Diseases

DNA Polymerase Iota Promotes Esophageal Squamous Cell Carcinoma Proliferation Through Erk-OGT-Induced G6PD Overactivation

Identification of a novel glycolysis-related signature to predict the prognosis of patients with breast cancer

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