ArticleClinical and experimental medicine2024
Deciphering glutamine metabolism patterns for malignancy and tumor microenvironment in clear cell renal cell carcinoma.
Article in Clinical and experimental medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Deciphering glutamine metabolic reprogramming: a novel therapeutic target ALDH18A1 in triple-negative breast cancer.Scientific reports · 2026Article
- Machine learning integration of multi-omics data develops a sarcomatoid-related renal cell carcinoma score (SARS) for prognosis stratification and guiding therapy.Translational andrology and urology · 2026Article
- Oxalate induces proliferation and mitochondrial metabolism in select clear cell renal cell carcinoma cell lines.BMC cancer · 2026Article
- Identification and evaluation of glutamine-related gene characteristics based on multi-omics to predict the prognosis of patients with colorectal cancer.Journal of translational medicine · 2026Article
- Article
- Nucleo-mitochondrial asymmetry profiles the proliferative engine and spatial niche reconstruction in clear cell renal cell carcinoma.Frontiers in immunology · 2026Article
- Common hub genes in Uremia and Kidney Renal Clear Cell Carcinoma (KIRC): their role in KIRC pathogenesis through activation of the citrate cycle pathway.BMC nephrology · 2025Article
- Renal cell carcinoma organoids for precision medicine: bridging the gap between models and patients.Journal of translational medicine · 2025Review
- Glutamine: a new strategy for targeted metabolic therapy in the tumor microenvironment.Cell death discovery · 2025Review
- Myo-Inositol Oxygenase (MIOX): A Pivotal Regulator and Therapeutic Target in Multiple Diseases.Current issues in molecular biology · 2025Review
- Article
- Identification of a novel prognostic and therapeutic prediction model in clear cell renal carcinoma based on Renin-angiotensin system related genes.Frontiers in endocrinology · 2025Article
- Identification and Characterization of Genes Associated with Intestinal Ischemia-Reperfusion Injury and Oxidative Stress: A Bioinformatics and Experimental Approach Integrating High-Throughput Sequencing, Machine Learning, and Validation.Journal of inflammation research · 2025Article
- A robust ammonia metabolism gene signature identified by machine learning predicts prognosis and immunotherapy response in clear cell renal cell carcinoma.Frontiers in oncology · 2025Article
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12 authors.
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Abstract
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer characterized by metabolic reprogramming. Glutamine metabolism is pivotal in metabolic reprogramming, contributing to the significant heterogeneity observed in ccRCC. Consequently, developing prognostic markers associated with glutamine metabolism could enhance personalized treatment strategies for ccRCC patients. This study obtained RNA sequencing and clinical data from 763 ccRCC cases sourced from multiple databases. Consensus clustering of 74 glutamine metabolism related genes (GMRGs)- profiles stratified the patients into three clusters, each of which exhibited distinct prognosis, tumor microenvironment, and biological characteristics. Then, six genes (SMTNL2, MIOX, TMEM27, SLC16A12, HRH2, and SAA1) were identified by machine-learning algorithms to develop a predictive signature related to glutamine metabolism, termed as GMRScore. The GMRScore showed significant differences in clinical prognosis, expression profile of immune checkpoints, abundance of immune cells, and immunotherapy response of ccRCC patients. Besides, the nomogram incorporating the GMRScore and clinical features showed strong predictive performance in prognosis of ccRCC patients. ALDH18A1, one of the GRMGs, exhibited elevated expression level in ccRCC and was related to markedly poorer prognosis in the integrated cohort, validated by proteomic profiling of 232 ccRCC samples from Fudan University Shanghai Cancer Center (FUSCC). Conducting western blotting, CCK-8, transwell, and flow cytometry assays, we found the knockdown of ALDH18A1 in ccRCC significantly promoted apoptosis and inhibited proliferation, invasion, and epithelial-mesenchymal transition (EMT) in two human ccRCC cell lines (786-O and 769-P). In conclusion, we developed a glutamine metabolism-related prognostic signature in ccRCC, which is tightly linked to the tumor immune microenvironment and immunotherapy response, potentially facilitating precision therapy for ccRCC patients. Additionally, this study revealed the key role of ALDH18A1 in promoting ccRCC progression for the first time.
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