High PYGL Expression Predicts Poor Prognosis in Human Gliomas

Zhao, Changyi; Hua, Chun-Hui; Li, Changhua; Zheng, Ruizhe; Li, Xinyuan

doi:10.3389/fneur.2021.652931

Cited by 15 publications

(9 citation statements)

References 40 publications

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“…PYGL is a hypoxia metabolism‐related gene. In cancer cells, the PYGL‐regulated glycogen metabolism process produces nicotinamide adenine dinucleotide phosphate (NADPH), which can scavenge ROS (Zhao et al, 2021). Excess uric acid can act as an antioxidant that can effectively scavenge increased oxygen radicals in the body (Tasaki et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Analysis of metabolomics and transcriptomics data in head and neck squamous cell carcinoma

Chen

et al. 2022

Oral Diseases

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The disease of HNSCC ranks 6th among common malignancies, accounting for 5% of all cancer cases and 2%-3% of all cancer deaths (Ferlay et al., 2019). The incidence, metastatic and mortality rates of HNSCC have increased rapidly in recent years. More than 550,000 people worldwide are diagnosed with HNSCC each year, and more than 380,000 die from the disease (Vermorken & Specenier, 2010).Today, we rely on imaging examinations such as magnetic resonance imaging (MRI), computed tomography (CT), positron emission computed tomography (PET) (Jorgensen et al., 2019), histological analysis of primary tumour biopsy and fine needle aspirate (FNA)

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Section: Discussionmentioning

confidence: 99%

Analysis of metabolomics and transcriptomics data in head and neck squamous cell carcinoma

Chen

et al. 2022

Oral Diseases

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“…There is evidence that points to PYGL being involved in glycogen degradation ( Zhan et al, 2021 ). The hypoxia metabolism gene PYGL was discovered to be upregulated in many malignancies, including breast cancers and head and neck squamous cell carcinomas ( Kawakubo-Yasukochi et al, 2021 ; Zhao et al, 2021 ). The glycogen degradation mediated by PYGL has been hypothesized to sustain the growth of cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Identification and immunological characterization of endoplasmic reticulum stress-related molecular subtypes in bronchopulmonary dysplasia based on machine learning

Tao

Mao²,

Hu³

et al. 2023

Front. Physiol.

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Introduction: Bronchopulmonary dysplasia (BPD) is a life-threatening lung illness that affects premature infants and has a high incidence and mortality. Using interpretable machine learning, we aimed to investigate the involvement of endoplasmic reticulum (ER) stress-related genes (ERSGs) in BPD patients.Methods: We evaluated the expression profiles of endoplasmic reticulum stress-related genes and immune features in bronchopulmonary dysplasia using the GSE32472 dataset. The endoplasmic reticulum stress-related gene-based molecular clusters and associated immune cell infiltration were studied using 62 bronchopulmonary dysplasia samples. Cluster-specific differentially expressed genes (DEGs) were identified utilizing the WGCNA technique. The optimum machine model was applied after comparing its performance with that of the generalized linear model, the extreme Gradient Boosting, the support vector machine (SVM) model, and the random forest model. Validation of the prediction efficiency was done by the use of a calibration curve, nomogram, decision curve analysis, and an external data set.Results: The bronchopulmonary dysplasia samples were compared to the control samples, and the dysregulated endoplasmic reticulum stress-related genes and activated immunological responses were analyzed. In bronchopulmonary dysplasia, two distinct molecular clusters associated with endoplasmic reticulum stress were identified. The analysis of immune cell infiltration indicated a considerable difference in levels of immunity between the various clusters. As measured by residual and root mean square error, as well as the area under the curve, the support vector machine machine model showed the greatest discriminative capacity. In the end, an support vector machine model integrating five genes was developed, and its performance was shown to be excellent on an external validation dataset. The effectiveness in predicting bronchopulmonary dysplasia subtypes was further established by decision curves, calibration curves, and nomogram analyses.Conclusion: We developed a potential prediction model to assess the risk of endoplasmic reticulum stress subtypes and the clinical outcomes of bronchopulmonary dysplasia patients, and our work comprehensively revealed the complex association between endoplasmic reticulum stress and bronchopulmonary dysplasia.

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“…This was not found for protein expression on the TMA, potentially due to the exclusion of necrotic tumour areas. Recently a similar analysis of the TCGA database also showed that PYGL was prognostic [ 62 ]. The higher expression we found of the PYGL compared to PYGB in GBM stem-like cultures suggests a role in plasticity and tumorigenesis [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Liver glycogen phosphorylase is upregulated in glioblastoma and provides a metabolic vulnerability to high dose radiation

et al. 2022

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Channelling of glucose via glycogen, known as the glycogen shunt, may play an important role in the metabolism of brain tumours, especially in hypoxic conditions. We aimed to dissect the role of glycogen degradation in glioblastoma (GBM) response to ionising radiation (IR). Knockdown of the glycogen phosphorylase liver isoform (PYGL), but not the brain isoform (PYGB), decreased clonogenic growth and survival of GBM cell lines and sensitised them to IR doses of 10–12 Gy. Two to five days after IR exposure of PYGL knockdown GBM cells, mitotic catastrophy and a giant multinucleated cell morphology with senescence-like phenotype developed. The basal levels of the lysosomal enzyme alpha-acid glucosidase (GAA), essential for autolysosomal glycogen degradation, and the lipidated forms of gamma-aminobutyric acid receptor-associated protein-like (GABARAPL1 and GABARAPL2) increased in shPYGL U87MG cells, suggesting a compensatory mechanism of glycogen degradation. In response to IR, dysregulation of autophagy was shown by accumulation of the p62 and the lipidated form of GABARAPL1 and GABARAPL2 in shPYGL U87MG cells. IR increased the mitochondrial mass and the colocalisation of mitochondria with lysosomes in shPYGL cells, thereby indicating reduced mitophagy. These changes coincided with increased phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase 2, slower ATP generation in response to glucose loading and progressive loss of oxidative phosphorylation. The resulting metabolic deficiencies affected the availability of ATP required for mitosis, resulting in the mitotic catastrophy observed in shPYGL cells following IR. PYGL mRNA and protein levels were higher in human GBM than in normal human brain tissues and high PYGL mRNA expression in GBM correlated with poor patient survival. In conclusion, we show a major new role for glycogen metabolism in GBM cancer. Inhibition of glycogen degradation sensitises GBM cells to high-dose IR indicating that PYGL is a potential novel target for the treatment of GBMs.

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High PYGL Expression Predicts Poor Prognosis in Human Gliomas

Cited by 15 publications

References 40 publications

Analysis of metabolomics and transcriptomics data in head and neck squamous cell carcinoma

Analysis of metabolomics and transcriptomics data in head and neck squamous cell carcinoma

Identification and immunological characterization of endoplasmic reticulum stress-related molecular subtypes in bronchopulmonary dysplasia based on machine learning

Liver glycogen phosphorylase is upregulated in glioblastoma and provides a metabolic vulnerability to high dose radiation

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