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

Abstract

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.

Multi-Omics Integration-Based Prioritisation of Competing Endogenous RNA Regulation Networks in Small Cell Lung Cancer: Molecular Characteristics and Drug Candidates

“…Similarly, Hamura et al reported that the modulation of GAA could affect cell proliferation and apoptosis and manipulate chemoresistance in pancreatic cancer cells via malfunctional mitochondria (74). The dysregulated metabolism of glucose in mitochondria is known as an adverse microenvironment in solid tumours, referred to as the Warburg effect, including glucose deprivation and lactic acidosis, potentially resulting in an elevated glycolytic activity in tumour cells (75)(76)(77)(78). Yan et al showed that glucose metabolic reprogramming improves SCLC cell proliferation and metastasis, suggesting it could be a potential regulatory strategy interfering with glucose metabolism in SCLC (56).…”

“…Yan et al showed that glucose metabolic reprogramming improves SCLC cell proliferation and metastasis, suggesting it could be a potential regulatory strategy interfering with glucose metabolism in SCLC (56). Considering the function of GAA, which catalyses the production of glucose from glycogen in lysosomes, altering the GAA expression or genetic status could inhibit tumorigenesis in SCLC through the lysosome pathway (56,(74)(75)(76)(77)(78). Interestingly, the DrugBank analysis showed that the drug targeting GAA was Trastuzumab-deruxtecan.…”

Renal Cell Cancer and Obesity

“…The loss of body weight appears to reduce the incidence of cancers [ 15 , 16 ]. It appears that renal cell carcinoma can be induced by metabolic changes resulting from numerous mutations within genes which products are involved in the regulation of metabolism, including mutations in the hypoxia pathway as well as the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway [ 17 , 18 ]. Lipidomic data indicate the enhanced accumulation of cholesterol and triglycerides in RCC cells.…”

Identification of co-expression hub genes for ferroptosis in kidney renal clear cell carcinoma based on weighted gene co-expression network analysis and The Cancer Genome Atlas clinical data

“…Lastly, Gao et al found that the TAZ/WNT10B axis may serve as biomarkers and therapeutic targets for KIRC immunotherapy 31 . Taken together, there are many studies on KIRC, but the current understanding of its pathogenesis, tumor progression, and metastasis is still imperfect, with many of its characteristics differing from other cancers 32 – 34 . Therefore, finding novel ferroptosis-related targets or pathways for the treatment of KIRC would two-fold curb the high recurrence rate and growing drug resistance of KIRC.…”