Upregulation of glucocorticoid receptor‐mediated glucose transporter 4 in enzalutamide‐resistant prostate cancer

Hoshi, Seiji; Meguro, Satoru; Imai, Hitomi; Matsuoka, Yuta; Yoshida, Yuki; Onagi, Akihumi; Tanji, Ryo; Honda-Takinami, Ruriko; Matsuoka, Kanako; Koguchi, Tomoyuki; Hata, Junya; Sato, Yuichi; Akaihata, Hidenori; Kataoka, Masao; Ogawa, Soichiro; Kojima, Yoshiyuki

doi:10.1111/cas.14865

Cited by 11 publications

(8 citation statements)

References 46 publications

(89 reference statements)

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“…As for solute carrier family-2-member-4-gene (SLC2A4), encoding glucose transporter-4-protein (GLUT4), it has been reported to serve as a novel therapeutic candidate for cancer treatment [ 50 ]. The inhibition of SLC2A4 could compromise cell proliferation and metastasis in breast cancer [ 51 ], prostate cancer [ 52 ], and gastric cancer [ 53 ]. Thus, the two signature genes sifted from this study could offer latent candidates to elucidate molecular mechanisms in liver cancer.…”

Section: Discussionmentioning

confidence: 99%

Novel Gene Signatures Promote Epithelial-Mesenchymal Transition (EMT) in Glucose Deprivation-Based Microenvironment to Predict Recurrence‐Free Survival in Hepatocellular Carcinoma

Huang

Liu

Gao

et al. 2023

Journal of Oncology

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Background. Current research studies have suggested that glucose deprivation (GD)-based tumor microenvironment (TME) can promote epithelial-mesenchymal transition (EMT) of tumor cells, leading to tumor invasion and metastasis. However, no one has yet studied detailedly the synthetic studies that include GD features in TME with EMT status. In our research, we comprehensively developed and validated a robust signature regarding GD and EMT status to provide prognostic value for patients with liver cancer. Methods. GD and EMT status were estimated with transcriptomic profiles based on WGCNA and t-SNE algorithms. Two cohorts of training (TCGA_LIHC) and validation (GSE76427) datasets were analyzed with the Cox regression and logistic regression analyses. We identified a 2-mRNA signature to establish a GD-EMT-based gene risk model for the prediction of HCC relapse. Results. Patients with significant GD-EMT status were divided into two subgroups: GDlow/EMTlow and GDhigh/EMThigh, with the latter having significantly worse recurrence-free survival ( P < 0.01 ). We employed the least absolute shrinkage and selection operator (LASSO) technique as a method for HNF4A and SLC2A4 filtering and constructing a risk score for risk stratification. In the multivariate analysis, this risk score predicted recurrence-free survival (RFS) in both the discovery and validation cohorts and remained valid in patients stratified by TNM stage and age at diagnosis. The nomogram that combines risk score and TNM stage as well as age produces improved performance and net benefits in the analysis of calibration and decision curves in training and validation groups. Conclusions. The GD-EMT-based signature predictive model may provide a prognosis classifier for HCC patients with a high risk of postoperative recurrence to decrease the relapse rate.

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Section: Discussionmentioning

confidence: 99%

Novel Gene Signatures Promote Epithelial-Mesenchymal Transition (EMT) in Glucose Deprivation-Based Microenvironment to Predict Recurrence‐Free Survival in Hepatocellular Carcinoma

Huang

Liu

Gao

et al. 2023

Journal of Oncology

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“…However, the role of AHSG in PCa is unclear. SLC2A4, also named GR-mediated glucose transporter 4 (GLUT4), is associated with glucose supply and metabolism, and it is upregulated with chronic Enz treatment ( 33 , 34 ). CYP2D6, a drug-metabolizing cytochrome P450 enzyme, is a critical pharmacogene involved in the metabolism of approximately 25% of commonly used drugs, and altered CYP2D6 function has been concerned with reduced drug efficacy ( 35 ).…”

Section: Discussionmentioning

confidence: 99%

A Metabolism-Related Gene Landscape Predicts Prostate Cancer Recurrence and Treatment Response

et al. 2022

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BackgroundProstate cancer (PCa) is the most common malignant tumor in men. Although clinical treatments of PCa have made great progress in recent decades, once tolerance to treatments occurs, the disease progresses rapidly after recurrence. PCa exhibits a unique metabolic rewriting that changes from initial neoplasia to advanced neoplasia. However, systematic and comprehensive studies on the relationship of changes in the metabolic landscape of PCa with tumor recurrence and treatment response are lacking. We aimed to construct a metabolism-related gene landscape that predicts PCa recurrence and treatment response.MethodsIn the present study, we used differentially expressed gene analysis, protein–protein interaction (PPI) networks, univariate and multivariate Cox regression, and least absolute shrinkage and selection operator (LASSO) regression to construct and verify a metabolism-related risk model (MRM) to predict the disease-free survival (DFS) and response to treatment for PCa patients.ResultsThe MRM predicted patient survival more accurately than the current clinical prognostic indicators. By using two independent PCa datasets (International Cancer Genome Consortium (ICGC) PCa and Taylor) and actual patients to test the model, we also confirmed that the metabolism-related risk score (MRS) was strongly related to PCa progression. Notably, patients in different MRS subgroups had significant differences in metabolic activity, mutant landscape, immune microenvironment, and drug sensitivity. Patients in the high-MRS group were more sensitive to immunotherapy and endocrine therapy, while patients in the low-MRS group were more sensitive to chemotherapy.ConclusionsWe developed an MRM, which might act as a clinical feature to more accurately assess prognosis and guide the selection of appropriate treatment for PCa patients. It is promising for further application in clinical practice.

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“…Furthermore, BIRC3 has also been identified as a glucocorticoid receptor (GR) regulated gene (122,123), although this was in the context of bronchial and pulmonary epithelial cells. The GR is also correlated with CRPC and PCa progression (124), whereby androgens can bind the GR to activate proliferation genes due to high homology between the AR and GR (125). Therefore, BIRC3 is not solely regulated by AR-V7 and crosstalk between the GR pathway should be considered.…”

Section: Birc3mentioning

confidence: 99%

A compendium of Androgen Receptor Variant 7 target genes and their role in Castration Resistant Prostate Cancer

et al. 2023

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Persistent androgen receptor (AR) signalling is the main driver of prostate cancer (PCa). Truncated isoforms of the AR called androgen receptor variants (AR-Vs) lacking the ligand binding domain often emerge during treatment resistance against AR pathway inhibitors such as Enzalutamide. This review discusses how AR-Vs drive a more aggressive form of PCa through the regulation of some of their target genes involved in oncogenic pathways, enabling disease progression. There is a pressing need for the development of a new generation of AR inhibitors which can repress the activity of both the full-length AR and AR-Vs, for which the knowledge of differentially expressed target genes will allow evaluation of inhibition efficacy. This review provides a detailed account of the most common variant, AR-V7, the AR-V7 regulated genes which have been experimentally validated, endeavours to understand their relevance in aggressive AR-V driven PCa and discusses the utility of the downstream protein products as potential drug targets for PCa treatment.

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Upregulation of glucocorticoid receptor‐mediated glucose transporter 4 in enzalutamide‐resistant prostate cancer

Cited by 11 publications

References 46 publications

Novel Gene Signatures Promote Epithelial-Mesenchymal Transition (EMT) in Glucose Deprivation-Based Microenvironment to Predict Recurrence‐Free Survival in Hepatocellular Carcinoma

Novel Gene Signatures Promote Epithelial-Mesenchymal Transition (EMT) in Glucose Deprivation-Based Microenvironment to Predict Recurrence‐Free Survival in Hepatocellular Carcinoma

A Metabolism-Related Gene Landscape Predicts Prostate Cancer Recurrence and Treatment Response

A compendium of Androgen Receptor Variant 7 target genes and their role in Castration Resistant Prostate Cancer

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