scholarly journals Renal Lipid Metabolism Abnormalities in Obesity and Clear Cell Renal Cell Carcinoma

Metabolites ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 608
Author(s):  
Ion Alexandru Bobulescu ◽  
Laurentiu M. Pop ◽  
Chinnadurai Mani ◽  
Kala Turner ◽  
Christian Rivera ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Metabolic Reprogramming ◽  
Future Research ◽  
Metabolic Disturbances ◽  
Intracellular Lipid ◽  
Cell Renal Cell Carcinoma ◽  
Potential Link

Clear cell renal cell carcinoma is the most common and deadly type of cancer affecting the kidney, and is characterized histologically by large intracellular lipid deposits. These deposits are thought to result from lipid metabolic reprogramming occurring in tumor cells, but the exact mechanisms and implications of these metabolic alterations are incompletely understood. Obesity is an independent risk factor for clear cell renal cell carcinoma, and is also associated with lipid accumulation in noncancerous epithelial cells of the proximal tubule, where clear cell renal cell carcinoma originates. This article explores the potential link between obesity-associated renal lipid metabolic disturbances and lipid metabolic reprogramming in clear cell renal cell carcinoma, and discusses potential implications for future research.

scholarly journals The Uniqueness of Clear Cell Renal Cell Carcinoma: Summary of the Process and Abnormality of Glucose Metabolism and Lipid Metabolism in ccRCC

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaochen Qi ◽  
Quanlin Li ◽  
Xiangyu Che ◽  
Qifei Wang ◽  
Guangzhen Wu
Keyword(s):  
Renal Cell Carcinoma ◽  
Lipid Metabolism ◽  
Glucose Metabolism ◽  
Cell Carcinoma ◽  
Kidney Cancer ◽  
Renal Cell ◽  
Cancer Metabolism ◽  
Clear Cell ◽  
Future Research ◽  
Cell Renal Cell Carcinoma

Kidney cancer is a cancer with an increasing incidence in recent years. Clear cell renal cell carcinoma (ccRCC) accounts for up to 80% of all kidney cancers. The understanding of the pathogenesis, tumor progression, and metastasis of renal carcinoma is not yet perfect. Kidney cancer has some characteristics that distinguish it from other cancers, and the metabolic aspect is the most obvious. The specificity of glucose and lipid metabolism in kidney cancer cells has also led to its being studied as a metabolic disease. As the most common type of kidney cancer, ccRCC has many characteristics that represent the specificity of kidney cancer. There are features that we are very concerned about, including the presence of lipid droplets in cells and the obesity paradox. These two points are closely related to glucose metabolism and lipid metabolism. Therefore, we hope to explore whether metabolic changes affect the occurrence and development of kidney cancer by looking for evidence of changes on expression at the genomic and protein levels in glucose metabolism and lipid metabolism in ccRCC. We begin with the representative phenomenon of abnormal cancer metabolism: the Warburg effect, through the collection of popular metabolic pathways and related genes in the last decade, as well as some research hotspots, including the role of ferroptosis and glutamine in cancer, systematically elaborated the factors affecting the incidence and metastasis of kidney cancer. This review also identifies the similarities and differences between kidney cancer and other cancers in order to lay a theoretical foundation and provide a valid hypothesis for future research.

scholarly journals Revealing potential lipid biomarkers in clear cell renal cell carcinoma using targeted quantitative lipidomics

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Wen Li ◽  
Xiaobin Wang ◽  
Xianbin Zhang ◽  
Peng Gong ◽  
Degang Ding ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Molecular Mechanisms ◽  
Clear Cell ◽  
Multiple Reaction Monitoring ◽  
Leading Edge ◽  
Lipid Classes ◽  
Metabolic Reprogramming ◽  
Cell Renal Cell Carcinoma

Abstract Background The high drug resistance and metabolic reprogramming of clear cell renal cell carcinoma (ccRCC) are considered responsible for poor prognosis. In-depth research at multiple levels is urgently warranted to illustrate the lipid composition, distribution, and metabolic pathways of clinical ccRCC specimens. Methods In this project, a leading-edge targeted quantitative lipidomic study was conducted using 10 pairs of cancerous and adjacent normal tissues obtained from ccRCC patients. Accurate lipid quantification was performed according to a linear equation calculated using internal standards. Qualitative and quantitative analyses of lipids were performed with multiple reaction monitoring analysis based on ultra-performance liquid chromatography (UPLC) and mass spectrometry (MS). Additionally, a multivariate statistical analysis was performed using data obtained on lipids. Results A total of 28 lipid classes were identified. Among them, the most abundant were triacylglycerol (TG), diacylglycerol (DG), phosphatidylcholine (PC), and phosphatidylethanolamine (PE). Cholesteryl ester (CE) was the lipid exhibiting the most considerable difference between normal samples and tumor samples. Lipid content, chain length, and chain unsaturation of acylcarnitine (CAR), CE, and DG were found to be significantly increased. Based on screening for variable importance in projection scores ≥1, as well as fold change limits between 0.5 and 2, 160 differentially expressed lipids were identified. CE was found to be the most significantly upregulated lipid, while TG was observed to be the most significantly downregulated lipid. Conclusion Based on the absolute quantitative analysis of lipids in ccRCC specimens, it was observed that the content and change trends varied in different lipid classes. Upregulation of CAR, CE, and DG was observed, and analysis of changes in the distribution helped clarify the causes of lipid accumulation in ccRCC and possible carcinogenic molecular mechanisms. The results and methods described herein provide a comprehensive analysis of ccRCC lipid metabolism and lay a theoretical foundation for cancer treatment.

scholarly journals Expression of AOX1 Predicts Prognosis of Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Luyang Xiong ◽  
Yuchen Feng ◽  
Wei Hu ◽  
Jiahong Tan ◽  
Shusheng Li ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Differentially Expressed Genes ◽  
Renal Cell ◽  
Clear Cell ◽  
Metabolic Reprogramming ◽  
Differentially Expressed ◽  
Normal Kidney ◽  
Cell Renal Cell Carcinoma ◽  
Cancer Management

Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer worldwide, and appropriate cancer biomarkers facilitate early diagnosis, treatment, and prognosis prediction in cancer management. However, an accurate biomarker for ccRCC is lacking. This study identified 356 differentially expressed genes in ccRCC tissues compared with normal kidney tissues by integrative analysis of eight ccRCC datasets. Enrichment analysis of the differentially expressed genes unveiled improved adaptation to hypoxia and metabolic reprogramming of the tumor cells. Aldehyde oxidase 1 (AOX1) gene was identified as a biomarker for ccRCC among all the differentially expressed genes. ccRCC tissues expressed significantly lower AOX1 than normal kidney tissues, which was further validated by immunohistochemistry at the protein level and The Cancer Genome Atlas (TCGA) data mining at the mRNA level. Higher AOX1 expression predicted better overall survival in ccRCC patients. Furthermore, AOX1 DNA copy number deletion and hypermethylation were negatively correlated with AOX1 expression, which might be the potential mechanism for its dysregulation in ccRCC. Finally, we illustrated that the effect of AOX1 as a tumor suppressor gene is not restricted to ccRCC but universally exists in many other cancer types. Hence, AOX1 may act as a potential prognostic biomarker and therapeutic target for ccRCC.

Metabolic reprogramming in clear cell renal cell carcinoma

2017 ◽  
Vol 13 (7) ◽  
pp. 410-419 ◽  
Author(s):  
Hiromi I. Wettersten ◽  
Omran Abu Aboud ◽  
Primo N. Lara ◽  
Robert H. Weiss
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Metabolic Reprogramming ◽  
Cell Renal Cell Carcinoma

scholarly journals Role of Metabolic Reprogramming of Long non-coding RNA in Clear Cell Renal Cell Carcinoma

2022 ◽  
Vol 13 (2) ◽  
pp. 691-705
Author(s):  
Huijie Zhang ◽  
Lei Yu ◽  
Jing Chen ◽  
Liting Liu ◽  
Xudong Yang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Metabolic Reprogramming ◽  
Cell Renal Cell Carcinoma ◽  
Non Coding Rna ◽  
Long Non Coding Rna

scholarly journals HIF-2α drives an intrinsic vulnerability to ferroptosis in clear cell renal cell carcinoma

2018 ◽  
Author(s):  
Yilong Zou ◽  
Michael J. Palte ◽  
Amy A. Deik ◽  
Haoxin Li ◽  
John K. Eaton ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cancer Therapeutics ◽  
Metabolic Reprogramming ◽  
Membrane Topology ◽  
List Type ◽  
Cell Renal Cell Carcinoma ◽  
Cell State

SUMMARYKidney cancers are characterized by extensive metabolic reprogramming and resistance to a broad range of anti-cancer therapies. By interrogating the Cancer Therapeutics Response Portal compound sensitivity dataset, we show that cells of clear-cell renal cell carcinoma (ccRCC) possess a lineage-specific vulnerability to ferroptosis that can be exploited by inhibiting glutathione peroxidase 4 (GPX4). Using genome-wide CRISPR screening and lipidomic profiling, we reveal that this vulnerability is driven by the HIF-2α–HILPDA pathway by inducing a polyunsaturated fatty acyl (PUFA)-lipid-enriched cell state that is dependent on GPX4 for survival and susceptible to ferroptosis. This cell state is developmentally primed by the HNF-1β–1-Acylglycerol-3-Phosphate O-Acyltransferase 3 (AGPAT3) axis in the renal lineage. In addition to PUFA metabolism, ferroptosis is facilitated by a phospholipid flippase TMEM30A involved in membrane topology. Our study uncovers an oncogenesis-associated vulnerability, delineates the underlying mechanisms and suggests targeting GPX4 to induce ferroptosis as a therapeutic opportunity in ccRCC.HIGHLIGHTSccRCC cells exhibit strong susceptibility to GPX4 inhibition-induced ferroptosisThe GPX4-dependent and ferroptosis-susceptible state in ccRCC is associated with PUFA-lipid abundanceThe HIF-2α–HILPDA axis promotes the selective deposition of PUFA-lipids and ferroptosis susceptibilityAGPAT3 selectively synthesizes PUFA-phospholipids and primes renal cells for ferroptosis

638: Macroscopic Tumor Necrosis is a Prognostic Indicator for Non-Metastatic Clear Cell Renal Cell Carcinoma

2007 ◽  
Vol 177 (4S) ◽  
pp. 214-214
Author(s):  
Sung Kyu Hong ◽  
Byung Kyu Han ◽  
In Ho Chang ◽  
June Hyun Han ◽  
Ji Hyung Yu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Tumor Necrosis ◽  
Clear Cell ◽  
Prognostic Indicator ◽  
Cell Renal Cell Carcinoma ◽  
Macroscopic Tumor
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