36-kDa Annexin A3 Isoform Negatively Modulates Lipid Storage in Clear Cell Renal Cell Carcinoma Cells

Bombelli, S; Torsello, B; Marco, S De; Lucarelli, Giuseppe; Cifola, Ingrid; Grasselli, Chiara; Strada, G; Bovo, Giorgio; Perego, R; Bianchi, Cristina

doi:10.1016/j.ajpath.2020.08.008

Cited by 77 publications

(51 citation statements)

References 32 publications

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“…The metabolic flux through glycolysis is partitioned, [22][23][24] and mitochondrial bioenergetics and oxidative phosphorylation are impaired, as well as lipid metabolism. 25,26 In particular, it has been shown that in ccRCC, Complex I is inhibited by NADH dehydrogenase 1 alpha subcomplex 4-like 2 (NDUFA4L2), a HIF-1 target gene encoding for a regulatory protein that attenuates mitochondrial oxygen consumption. 26 The most common and malignant histological subtype of RCC is ccRCC, which is insensitive to radiotherapy and has high rates of local invasion, metastasis, and acquired chemoresistance.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Roles of Phosphofructokinase Platelet in Clear Cell Renal Cell Carcinoma and Correlation with Immune Infiltration

Liu

et al. 2021

IJGM

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Background: Abnormal expression of phosphofructokinase platelet (PFKP) has been reported in various cancer types. However, the role of PFKP in clear cell renal cell carcinoma (ccRCC) remains unclear. Methods: In this study, the PFKP expression levels in various cancers were systemically described by integrating multiple kinds of publicly available databases. The relationship between PFKP expression and clinical prognosis of ccRCC patients was analyzed based on the TCGA database. Furthermore, PFKP-related genes and the top 10 hub genes were identified. The enrichment analysis, PPI network, and the relationship between PFKP and tumor-infiltrating immune cells were conducted to explore why PFKP was associated with clinical outcomes in ccRCC patients. Results: PFKP was significantly highly expressed in kidney cancer, especially in ccRCC. Moreover, patients with low expression of PFKP were correlated with poor 5-year and 10year overall survival (OS) (P < 0.05). Low PFKP expression was a risk factor associated with decreased OS in subgroups including males, females, grade 3-4, and stage III-IV (all P < 0.05). GO and KEGG enrichment analyses showed that 10 hub genes were mainly enriched in the tumor immune response. Finally, PFKP expression level was highly correlated with the infiltration of B cell, CD8 + T cell, CD4 + T cell, macrophage, neutrophil, and dendritic cell. Conclusion:In short, our findings suggested that PFKP is highly expressed in ccRCC significantly and facilitated tumor immune response which in turn associated with a good prognosis.

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Section: Discussionmentioning

confidence: 99%

Prognostic Roles of Phosphofructokinase Platelet in Clear Cell Renal Cell Carcinoma and Correlation with Immune Infiltration

Liu

et al. 2021

IJGM

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“…Apart from exhibition of genetic mutations and epigenetic regulation [ 44 ], ccRCC is a metabolic disease that involves metabolic reprogramming during tumorigenesis and progression [ 45 ]. Lipid accumulation in ccRCC is related to the absorption and excretion of lipid metabolites [ 46 , 47 ]. The role of considerable amounts of lipid droplets (LDs) accumulated in ccRCC remains controversial [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

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

Wang

Zhang

et al. 2021

Lipids Health Dis

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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.

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“…Oil Red O (ORO) staining was performed on formalin-fixed primary cells and tissue samples, as previously described [ 19 , 58 ].…”

Section: Methodsmentioning

confidence: 99%

Integration of Lipidomics and Transcriptomics Reveals Reprogramming of the Lipid Metabolism and Composition in Clear Cell Renal Cell Carcinoma

et al. 2020

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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.

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36-kDa Annexin A3 Isoform Negatively Modulates Lipid Storage in Clear Cell Renal Cell Carcinoma Cells

Cited by 77 publications

References 32 publications

Prognostic Roles of Phosphofructokinase Platelet in Clear Cell Renal Cell Carcinoma and Correlation with Immune Infiltration

Prognostic Roles of Phosphofructokinase Platelet in Clear Cell Renal Cell Carcinoma and Correlation with Immune Infiltration

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

Integration of Lipidomics and Transcriptomics Reveals Reprogramming of the Lipid Metabolism and Composition in Clear Cell Renal Cell Carcinoma

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