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

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.

Metabolites ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 509
Author(s):  
Giuseppe Lucarelli ◽  
Matteo Ferro ◽  
Davide Loizzo ◽  
Cristina Bianchi ◽  
Daniela Terracciano ◽  
...  

Clear cell renal cell carcinoma (ccRCC) is fundamentally a metabolic disease. Given the importance of lipids in many cellular processes, in this study we delineated a lipidomic profile of human ccRCC and integrated it with transcriptomic data to connect the variations in cancer lipid metabolism with gene expression changes. Untargeted lipidomic analysis was performed on 20 ccRCC and 20 paired normal tissues, using LC-MS and GC-MS. Different lipid classes were altered in cancer compared to normal tissue. Among the long chain fatty acids (LCFAs), significant accumulations of polyunsaturated fatty acids (PUFAs) were found. Integrated lipidomic and transcriptomic analysis showed that fatty acid desaturation and elongation pathways were enriched in neoplastic tissue. Consistent with these findings, we observed increased expression of stearoyl-CoA desaturase (SCD1) and FA elongase 2 and 5 in ccRCC. Primary renal cancer cells treated with a small molecule SCD1 inhibitor (A939572) proliferated at a slower rate than untreated cancer cells. In addition, after cisplatin treatment, the death rate of tumor cells treated with A939572 was significantly greater than that of untreated cancer cells. In conclusion, our findings delineate a ccRCC lipidomic signature and showed that SCD1 inhibition significantly reduced cancer cell proliferation and increased cisplatin sensitivity, suggesting that this pathway can be involved in ccRCC chemotherapy resistance.


2018 ◽  
Vol 22 (7) ◽  
pp. 873-877
Author(s):  
E. A. Klimentova ◽  
I. R. Gilyazova ◽  
A. A. Izmailov ◽  
I. M. Sultanov ◽  
M. A. Bermisheva ◽  
...  

Kidney cancer is a heterogeneous group of malignant tumors, the vast majority of which are renal cell carcinomas (RCC) of various morphological types, of which the most common is the clear cell renal cell carcinoma (ccRCC). Particular attention in the carcinogenesis of the ccRCC is given to a number of tumor suppressor genes located on the short arm of the third chromosome. One of these genes, which are inactivated in the case of ccRCC is the PBRM1 gene encoding the PBAF SWI/SNF subunit of the chromatin remodeling complex, BAF180. The PBRM1 gene is located on the short arm of the third chromosome in the 3p21 region near the von Hippel-Lindau gene (VHL), the mutation in which is the main event in the occurrence of ccRCC. The aim of our investigation is identification of changes in the nucleotide sequence of the PBRM1 tumor suppressor gene in patients with ccRCC. 210 pairs of DNA samples isolated from ccRCC tissue were studied. Analysis of changes in the nucleotide sequence of DNA was carried out by HRM analysis and direct sequencing. In the PBRM1 gene, two somatic mutations were found (c.233G>A (p.D45N) in exon 2, c.1675-1676delTC in exon 15) which were not described previously, and one known polymorphic variant rs17264436 (in exon 23). The frequency of detected mutations was 0.95 % of cases. Analysis of the allelic association for the polymorphic locus rs17264436 showed a statistically significant increase in the risk of developing advanced kidney cancer in carriers of allele rs17264436*A, which can be used in the development of prognostic marker panels. Perhaps the low frequency of mutations in the samples we studied is due to the fact that the inactivation of the PBRM1 gene takes place in other ways, and may also be due to the ethno-specificity of the studied group of patients.


2016 ◽  
Vol 49 (4) ◽  
pp. 1569-1575 ◽  
Author(s):  
Jiwei Huang ◽  
Wen Kong ◽  
Jin Zhang ◽  
Yonghui Chen ◽  
Wei Xue ◽  
...  

2019 ◽  
Vol 19 (1) ◽  
pp. 40-47 ◽  
Author(s):  
Zhenlong Wang ◽  
Lei Tao ◽  
Yuquan Xue ◽  
Li Xue ◽  
Ziming Wang ◽  
...  

Background: Kidney cancer is one of the most common cancers worldwide. Recent studies have suggested that single nucleotide polymorphisms (SNPs) in autophagy-related gene are associated with the risk of kidney cancer. Objective: This study was undertaken to investigate the association of autophagyrelated gene 7 (ATG7) polymorphisms with the risk of clear cell renal cell carcinoma (ccRCC) in the Chinese Han population. Methods: A significant association was observed between allele A of rs6442260 and ccRCC risk (OR = 0.76, 95% CI: 0.58-0.99, p = 0.039). Genetic model analysis revealed that rs2606736 (OR = 0.57, 95% CI: 0.34-0.95, p = 0.031) and rs6442260 (OR = 0.44, 95% CI: 0.22-0.90, p = 0.021) were associated with decreased risk of ccRCC under recessive model. Age stratification analysis showed that rs2606736 (OR = 0.67, 95% CI: 0.46-0.98, p = 0.036) and rs6442260 (OR = 0.26, 95% CI: 0.07-0.89, p = 0.014) were significantly decreased risk of ccRCC under the log-additive model in age > 55 years old and ≤ 55 years old, respectively. Results: A significant association was observed between allele A of rs6442260 and ccRCC risk (OR = 0.76, 95% CI: 0.58-0.99, p = 0.039). Genetic model analysis revealed that rs2606736 (OR = 0.57, 95% CI: 0.34-0.95, p = 0.031) and rs6442260 (OR = 0.44, 95% CI: 0.22-0.90, p = 0.021) were associated with decreased risk of ccRCC under recessive model. Age stratification analysis showed that rs2606736 (OR = 0.67, 95% CI: 0.46-0.98, p = 0.036) and rs6442260 (OR = 0.26, 95% CI: 0.07-0.89, p = 0.014) were significantly decreased risk of ccRCC under the log-additive model in age > 55 years old and ≤ 55 years old, respectively. Conclusions: This study indicated that ATG7 polymorphisms (rs2606736 and rs6442260) have a protective role for ccRCC risk. Further large sample size and functional assays are needed to confirm our findings and reveal the role of ATG7 polymorphisms in ccRCC carcinogenesis.


Tumor Biology ◽  
2015 ◽  
Vol 37 (6) ◽  
pp. 8121-8130 ◽  
Author(s):  
Zuohui Zhao ◽  
Jiaju Lu ◽  
Liping Han ◽  
Xiaoqing Wang ◽  
Quanzhan Man ◽  
...  

2019 ◽  
Vol 10 (1) ◽  
pp. 35-41
Author(s):  
Oleg I. Kit ◽  
Elena M. Franciyants ◽  
Aleksey N. Shevchenko ◽  
Anna A. Breus ◽  
Irina V. Neskubina ◽  
...  

Objective:study of components of an insulin-like signaling pathway in kidney tissues in local and advanced clear cell renal cell carcinoma depending on the gender of patients.Materials and methods:the object of the study was conditionally intact kidney tissue and tumor and perifocal tissues obtained during the surgical treatment of 100 patients with histologically confirmed clear cell kidney cancer (local cancer (Т1-2N0М0) n=50, advanced cancer (Т3-4N0М1) n=50). Levels of the IGF-1, IGF-2, IGFBP-1 and IGFBP-2 growth factors (Mediagnost, Germany) and STH-releasing (Peninsula Laboratories International, USA) were determined by ELISA using standard test systems. The results were analyzed using Statistica 6.0 (Stat-Soft, 2001).Results:levels of IGFВР-2 and STH-releasing in conditionally intact tissues in women were 44% and 40% lower than in men, respectively. The IGFВР-2 level in perifocal tissues of women was 38% higher than in men, while STH-releasing was lower by 1.9 times. Tumor tissues of local kidney cancer in women showed significant decrease in IGF-1 by 25%, IGFВР-1 by 29% and IGFВР-2 by 2 times. Levels of IGFBP-1 and IGFBP-2 in conditionally intact tissues of women with advanced cancer were 2 and 2.7 times lower, respectively, compared to men. IGFBP-2 and STH-releasing in perifocal tissues of women were increased by 43.8% and 44.6%, respectively. In tumor tissues of women with advanced kidney cancer, levels of IGF-1 were 1.7 times higher, IGF-2 – 31% lower, IGFBP-2 – 2.8 times lower and STH-releasing – 36% lower, compared to men.Conclusions:IGFBP-2 in all studied kidney tissues in local and advanced cancer was an identically variable index characterizing gender differences in the body’s reaction to the tumor process.


2020 ◽  
Vol 81 (01) ◽  
pp. e10-e14
Author(s):  
Johannes Dietterle ◽  
Clara Frydrychowicz ◽  
Wolf Müller ◽  
Karl-Titus Hoffmann ◽  
Katja Jähne ◽  
...  

Abstract Background Meningioma accounts for more than 35% of all diagnosed brain tumors of the central nervous system and, moreover, it is the most common benign recipient of tumor-to-tumor metastasis. Several cases with tumor-to-meningioma metastasis by breast, lung, and intestinal cancer have been described before. Case description The case of a patient with a longstanding history of multiple meningiomas (n = 4) that suddenly became symptomatic and progressive in size is presented. Following extirpation of the two largest meningiomas, a histological examination revealed two separate tumor-to-meningioma metastases of clear cell renal cell carcinoma that was undiagnosed before. Post-surgical computed tomography scan then confirmed tumor-suspect lesions in both kidneys. After recovery and rehabilitation, adjuvant radio-chemo-therapy was applied according to protocols for kidney cancer. No other tumor-to-tumor-suspect event occurred since then for the remaining two meningiomas. Conclusion Review of literature and our case strengthens the idea of meningioma as a favorable premetastatic niche. Considering that the patient lived with a stable disease for many years, a sudden progress of tumor size in association with neurological deterioration was highly suspected for malign involvement, including the possibility of tumor-to-tumor metastasis. Physicians should be aware about this phenomenon and treat patients accordingly to the underlying disease.


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