Heterogeneity and function of cancer-associated fibroblasts in renal cell carcinoma

Tang, Haijia; Xu, Wen; Lu, Jiahe; Anwaier, Aihetaimujiang; Ye, Dingwei; Zhang, Ye

doi:10.1016/j.jncc.2023.04.001

Cited by 3 publications

(1 citation statement)

References 31 publications

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“…It is widely accepted that this metabolic adaptation confers growth advantages to tumor cells, aids in evading apoptosis, and contributes to the progression of cancer in vivo [ 16 ]. Moreover, glycolysis induces cancer-associated fibroblasts to secrete lactate and hydrogen ions, fostering an immune-suppressive microenvironment [ 17 ]. RCC, a prevalent tumor within the urinary system, serves as a prime example of metabolic reprogramming.…”

Section: Introductionmentioning

confidence: 99%

Deciphering glutamine metabolism patterns for malignancy and tumor microenvironment in clear cell renal cell carcinoma

Wu,

Li,

Chen

et al. 2024

Clin Exp Med

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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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Section: Introductionmentioning

confidence: 99%

Deciphering glutamine metabolism patterns for malignancy and tumor microenvironment in clear cell renal cell carcinoma

Wu,

Li,

Chen

et al. 2024

Clin Exp Med

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Deciphering the implications of mitophagy-related signatures in clinical outcomes and microenvironment heterogeneity of clear cell renal cell carcinoma

Xiang,

Liu,

Liu

et al. 2023

J Cancer Res Clin Oncol

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Genetic Variation and Metabolic Basis of Kidney Cancer: New Opportunities for Targeted Therapy

Urmantsev,

Tavabilov,

Bakeev

2024

Kreativnaâ hirurgiâ i onkologiâ

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Renal cell carcinoma (RCC) has previously been considered as a single disease. However, it is currently characterized as a heterogeneous group of tumors that differ in histological features, genetic abnormalities, and variable clinical course. In normal cells, energy is produced by the cleavage of chemical bonds in nutrients through the oxidation of fats, proteins, or carbohydrates. Mutational alterations in genes associated with RCC, including VHL, FLCN, PTEN and SDH, lead to abnormal cellular adaptation to changes in oxygen status, iron metabolism and nutrients. The present paper reviews the known genetic abnormalities observed in RCC and their impact on metabolic alterations. Understanding the genetic and metabolic mechanisms underlying RCC is crucial for the development of effective therapies. Targeting specific genetic abnormalities or metabolic pathways represents a promising approach to the RCC treatment. In addition, studies into the metabolic basis of RCC contribute to the development of new biomarkers for early diagnosis and monitoring of the disease. Moreover, investigating the role of VHL, FLCN, PTEN, and SDH genes in the development of RCC provides valuable information on the molecular mechanisms behind the disease. As a result, it may lead to the development of new treatment strategies aimed at restoring the normal function of these genes or compensating for their abnormalities. Overall, an integrated approach to the study of RCC that considers genetic, metabolic, and clinical aspects will ensure that more effective treatments are developed and prognosis for patients with this disease are improved.

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Heterogeneity and function of cancer-associated fibroblasts in renal cell carcinoma

Cited by 3 publications

References 31 publications

Deciphering glutamine metabolism patterns for malignancy and tumor microenvironment in clear cell renal cell carcinoma

Deciphering glutamine metabolism patterns for malignancy and tumor microenvironment in clear cell renal cell carcinoma

Deciphering the implications of mitophagy-related signatures in clinical outcomes and microenvironment heterogeneity of clear cell renal cell carcinoma

Genetic Variation and Metabolic Basis of Kidney Cancer: New Opportunities for Targeted Therapy

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