Role of copper ionophore–induced death in immune microenvironment and clinical prognosis of ccRCC: An integrated analysis

Xia, Shunyao; Jia, Haixing; Qian, Zhipeng; Xiu, Youcheng

doi:10.3389/fgene.2022.994999

Cited by 3 publications

(3 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Numerous past studies have identi ed the importance of cuproptosis-related genes in the ccRCC immune microenvironment and can predict OS in patients with ccRCC [49,50]. Chen's and Zhang's study showed that high expression of FDX1 was associated with a better prognosis of renal clear cell carcinoma and could be used as a potential prognostic indicator and therapeutic target for ccRCC [51,52].…”

Section: Discussionmentioning

confidence: 99%

Cuproptosis related gene PDHB was identified as a biomarker and its up-regulation inhibited the invasion of renal clear cell carcinoma

Wang

Yang

et al. 2023

Preprint

View full text Add to dashboard Cite

Background Cuproptosis is a newly discovered programmed cell death dependent on mitochondrial respiratory disorder induced by copper overload. PDHB is one of the genes responsible for cuproptosis and is a nuclear encoded pyruvate dehydrogenase, an enzyme that catalyzes the conversion of pyruvate to acetyl coenzyme A. However, the mechanism of PDHB in renal clear cell carcinoma remains unclear. Methods We used data from TCGA and GEO to assess the expression of PDHB in normal and tumor tissues. We analysed the relationship between PDHB and somatic mutations and immune infiltration. Finally, we explored the impact of overexpressed PDHB on renal clear cell carcinoma. Results PDHB is lowly expressed in tumor tissue and reduced in high-grade tumors. Highly expressed PDHB has a better prognosis in ccRCC. In ccRCC, low PDHB expression may be associated with higher VHL, PBRM1 and KDM5C mutations. Addition of copper chloride to the 786-O cell line resulted in inhibition of cell growth and increased expression of the cuproptosis genes DLAT, PDHB and FDX1. Finally, the experiments verified that overexpression of PDHB inhibited the proliferation and migration of ccRCC cells. Conclusion Our results demonstrate that elevated PDHB expression inhibits the proliferation, migration and invasion of renal clear cell carcinoma cells, improves the prognosis of renal cancer patients and may provide a new therapeutic strategy for patients with advanced renal cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Cuproptosis related gene PDHB was identified as a biomarker and its up-regulation inhibited the invasion of renal clear cell carcinoma

Wang

Yang

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Numerous previous studies have identified the importance of cuproptosis-related genes in the ccRCC immune microenvironment and can predict OS in patients with ccRCC [ 51 , 52 ]. Chen et al and Zhang et al reported that higher expression of FDX1 was associated with a better prognosis of renal clear cell carcinoma and could be used as a potential prognostic indicator and therapeutic target for ccRCC [ 53 , 54 ].…”

Section: Discussionmentioning

confidence: 99%

Cuproptosis related gene PDHB is identified as a biomarker inversely associated with the progression of clear cell renal cell carcinoma

Wang,

Yang,

et al. 2023

BMC Cancer

View full text Add to dashboard Cite

Background Cuproptosis is a newly discovered programmed cell death dependent on mitochondrial respiratory disorder induced by copper overload. Pyruvate dehydrogenase E1 subunit beta (PDHB) is one of the cuproptosis genesand is a nuclear-encoded pyruvate dehydrogenase, which catalyzes the conversion of pyruvate to acetyl coenzyme A. However, the mechanism of PDHB in clear cell renal cell carcinoma (ccRCC) remains unclear. Methods We used data from TCGA and GEO to assess the expression of PDHB in normal and tumor tissues. We further analyzed the relationship between PDHB and somatic mutations and immune infiltration. Finally, we preliminarily explored the impact of PDHB on ccRCC. Results The expression level of PDHB was lower in tumor tissue compared with normal tissue. Meanwhile, the expression level of PDHB was also lower in high-grade tumors than low-grade tumors. PDHB is positively correlated with prognosis in ccRCC. Furthermore, PDHB may be associated with decreased risk of VHL, PBRM1 and KDM5C mutations. In 786-O cells, copper chloride could promote the expression of cuproptosis genes (DLAT, PDHB and FDX1) and inhibit cell growth. Last but not least, we found that PDHB could inhibit the proliferation and migration of ccRCC cells. Conclusion Our results demonstrated that PDHB could inhibit the proliferation, migration and invasion in ccRCC cells, which might be a prognostic predictor of ccRCC. Targeting this molecular might provide a new therapeutic strategy for patients with advanced ccRCC.

show abstract

“…One of the most promising therapeutic modalities is cancer immunotherapy (106), and research on ICI, in particular, has advanced quickly (107). Current therapeutic approaches aim to selectively promote cancer cell death and prevent harming normal cells because cancer is characterized by dysregulated cell death and altered inflammatory responses (108). The need for copper is greater in cancer cells compared to normal cells.…”

Section: Opportunities For Cuproptosis Cancer Treatmentmentioning

confidence: 99%

Cuproptosis: emerging biomarkers and potential therapeutics in cancers

Wang,

Zheng,

et al. 2023

Front. Oncol.

View full text Add to dashboard Cite

The sustenance of human life activities depends on copper, which also serves as a crucial factor for vital enzymes. Under typical circumstances, active homeostatic mechanisms keep the intracellular copper ion concentration low. Excess copper ions cause excessive cellular respiration, which causes cytotoxicity and cell death as levels steadily rise above a threshold. It is a novel cell death that depends on mitochondrial respiration, copper ions, and regulation. Cuproptosis is now understood to play a role in several pathogenic processes, including inflammation, oxidative stress, and apoptosis. Copper death is a type of regulatory cell death(RCD).Numerous diseases are correlated with the development of copper homeostasis imbalances. One of the most popular areas of study in the field of cancer is cuproptosis. It has been discovered that cancer angiogenesis, proliferation, growth, and metastasis are all correlated with accumulation of copper ions. Copper ion concentrations can serve as a crucial marker for cancer development. In order to serve as a reference for clinical research on the product, diagnosis, and treatment of cancer, this paper covers the function of copper ion homeostasis imbalance in malignant cancers and related molecular pathways.

show abstract

Role of copper ionophore–induced death in immune microenvironment and clinical prognosis of ccRCC: An integrated analysis

Cited by 3 publications

References 36 publications

Cuproptosis related gene PDHB was identified as a biomarker and its up-regulation inhibited the invasion of renal clear cell carcinoma

Cuproptosis related gene PDHB was identified as a biomarker and its up-regulation inhibited the invasion of renal clear cell carcinoma

Cuproptosis related gene PDHB is identified as a biomarker inversely associated with the progression of clear cell renal cell carcinoma

Cuproptosis: emerging biomarkers and potential therapeutics in cancers

Contact Info

Product

Resources

About