A glycolysis-related gene signature predicts prognosis of patients with esophageal adenocarcinoma

Kang, Huafeng; Wang, Nan; Wang, Xuan; Lin, Shuai; Mao, Guochao; Liu, Di; Dang, Chengxue; Zhou, Zhangjian

doi:10.18632/aging.104206

Cited by 20 publications

(18 citation statements)

References 42 publications

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“…We further investigated the impact of NVP-BEZ235 on glycolytic gene expression given the robust enrichment of these genes in control samples (ES = 63, p < 0.001, Table S1). GSEA was carried out for the glycolysis C1 (hallmark gene set) and C2 gene sets (curated gene sets), including the KEGG_GLYCOLYSIS_GLUCONEOGENESIS and HALLMARK_GLYCOLYSIS collections available in the MSigDB (https://www.gsea-msigdb.org/gsea/msigdb/genesets.jsp, accessed on 27 September 2020) [39]. GSEA indicated that glycolytic gene sets were significantly enriched in the control (DMSO samples) compared to NVP-BEZ235-treated samples (p < 0.05) in KEGG_GLYCOLYSIS_GLUCONEOGENESIS and HALLMARK_GLYCOLYSIS (Figure 1a,c and Table S3).…”

Section: Nvp-bez235 Treatment Reduced Glycolytic Gene Expression In Gbm Cellsmentioning

confidence: 99%

PI3K Pathway Inhibition with NVP-BEZ235 Hinders Glycolytic Metabolism in Glioblastoma Multiforme Cells

Udawant

Litif

Lopez

et al. 2021

Cells

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Glioblastoma (GBM) is the most lethal primary brain cancer that lacks effective molecular targeted therapies. The PI3K/AKT/mTOR pathway is activated in 90% of all Glioblastoma multiforme (GBM) tumors. To gain insight into the impact of the PI3K pathway on GBM metabolism, we treated U87MG GBM cells with NVP-BEZ235 (PI3K and mTOR a dual inhibitor) and identified differentially expressed genes with RNA-seq analysis. RNA-seq identified 7803 differentially regulated genes in response to NVP-BEZ235. Gene Set Enrichment Analysis (GSEA) identified two glycolysis-related gene sets that were significantly enriched (p < 0.05) in control samples compared to NVP-BEZ235-treated samples. We validated the inhibition of glycolytic genes by NVP-BEZ235 and examined the impact of the FOXO1 inhibitor (AS1842856) on these genes in a set of GBM cell lines. FOXO1 inhibition alone was associated with reduced LDHA expression, but not ENO1 or PKM2. Bioinformatics analyses revealed that PI3K-impacted glycolytic genes were over-expressed and co-expressed in GBM clinical samples. The elevated expression of PI3K-impacted glycolytic genes was associated with poor prognosis in GBM based on Kaplan–Meier survival analyses. Our results suggest novel insights into hallmark metabolic reprogramming associated with the PI3K-mTOR dual inhibition.

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Section: Nvp-bez235 Treatment Reduced Glycolytic Gene Expression In Gbm Cellsmentioning

confidence: 99%

PI3K Pathway Inhibition with NVP-BEZ235 Hinders Glycolytic Metabolism in Glioblastoma Multiforme Cells

Udawant

Litif

Lopez

et al. 2021

Cells

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“…The increase in metabolic activity is closely associated with tumor aggressiveness, and higher activated glycolysis indicates a poor prognosis for tumor patients. Patient prognosis was assessed in numerous studies by establishing prognostic risk signatures that combined multiple metabolism-related genes ( 21 , 22 ). Targeting tumor metabolism was proposed to hopefully improve patient prognosis.…”

Section: Discussionmentioning

confidence: 99%

PGK1 Is a Key Target for Anti-Glycolytic Therapy of Ovarian Cancer: Based on the Comprehensive Analysis of Glycolysis-Related Genes

Gou

Liu

et al. 2021

Front. Oncol.

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Reprogramming of energy metabolism is a key hallmark of cancer, which provides a new research perspective for exploring the development of cancer. However, the most critical target of anti-glycolytic therapy for ovarian cancer remains unclear. Therefore, in the present study, Oncomine, GEPIA, and HPA databases, combined with clinical specimens of different histological types of ovarian cancer were used to comprehensively evaluate the expression levels of glycolysis-related metabolite transporters and enzymes in ovarian cancer. We selected phosphoglycerate kinase 1 (PGK1), which showed the greatest prognostic value in the Kaplan-Meier Plotter database, for subsequent validation. Immunochemistry assays confirmed that PGK1 was highly expressed in ovarian cancer. The PGK1 expression level was an independent risk factor for the survival and prognosis of patients with ovarian cancer. Functional analysis showed that the PGK1 expression level was positively correlated with the infiltration of neutrophils. Cell experiments confirmed that inhibiting PGK1 expression in ovarian cancer cells could reduce the epithelial-mesenchymal transition (EMT) process, resulting in loss of cell migration and invasion ability. The small molecule NG52 dose-dependently inhibited the proliferation of ovarian cancer cells. In addition, NG52 reduced the EMT process and reversed the Warburg effect by inhibiting PGK1 activity. Therefore, PGK1 is an attractive molecular target for anti-glycolytic therapy of ovarian cancer.

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“…STMN1 is an oncogene that is highly upregulated in many tumors and associated with tumor growth. A study found STMN1 expression acted as glycolysis-related gene signature and predicted prognosis of patients with esophageal adenocarcinoma [ 23 ]. Another study identified five glycolysis-related mRNAs (GYS2, STMN1, PPFIA4, KDELR3, and ABCB6) which were associated with patients experience biochemical recurrence (BCR) after radical prostatectomy (RP) in patients with prostate adenocarcinoma [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Circβ-catenin promotes tumor growth and Warburg effect of gallbladder cancer by regulating STMN1 expression

Wang

Tong

et al. 2021

Cell Death Discov.

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Gallbladder cancer (GBC) is the most malignant cancer of the biliary tract cancer and presents poor prognosis. CircRNAs have been identified as critical regulators of multiple stages in tumor progression. In the study, we first demonstrated that circular RNA circβ-catenin expression was upregulated in GBC tissues when compared to adjacent normal tissues and associated with advanced clinical stage and poor prognosis in GBC patients. Silencing of circβ-catenin obviously suppressed GBC cell proliferation and cell cycle progression in vitro, but circβ-catenin overexpression had the opposite effects. In vivo, silencing of circβ-catenin inhibited tumor growth. Furthermore, we also found that circβ-catenin promoted GBC cell lactate production, pyruvate production, ATP quantity, and extracellular acidification rate (ECAR), which suggested that circβ-catenin regulated Warburg effect in GBC. Mechanistic analysis further highlighted that circβ-catenin promoted Stathmin 1 (STMN1) expression through sponging miR-223 in GBC progression. In addition, knockdown of STMN1 inhibited cell growth and Warburg effect in GBC. In summary, our findings indicated that circβ-catenin/miR-223/STMN1 axis could regulate cell growth and Warburg effect in GBC. Targeting circβ-catenin might be a potential therapeutic strategy for GBC.

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A glycolysis-related gene signature predicts prognosis of patients with esophageal adenocarcinoma

Cited by 20 publications

References 42 publications

PI3K Pathway Inhibition with NVP-BEZ235 Hinders Glycolytic Metabolism in Glioblastoma Multiforme Cells

PI3K Pathway Inhibition with NVP-BEZ235 Hinders Glycolytic Metabolism in Glioblastoma Multiforme Cells

PGK1 Is a Key Target for Anti-Glycolytic Therapy of Ovarian Cancer: Based on the Comprehensive Analysis of Glycolysis-Related Genes

Circβ-catenin promotes tumor growth and Warburg effect of gallbladder cancer by regulating STMN1 expression

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