A Novel Cuproptosis-Related Prognostic Gene Signature and Validation of Differential Expression in Clear Cell Renal Cell Carcinoma

Bian, Zuguang; Fan, Rong; Xie, Lingmin

doi:10.3390/genes13050851

Cited by 241 publications

(215 citation statements)

References 49 publications

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“…In previous studies, it was found that the copper depletion caused by tetrathiomolybdate (TM) influences immune response, and intratumoral copper ions may be able to regulate PD-L1 expression and influence tumor immune escape ( 9 , 10 ). Consistently, the latest report of Bian et al also showed that cuproptosis was significantly correlated with immune cell infiltration and PD-1 expression in clear cell renal cell carcinoma (ccRCC) ( 11 ). In addition, copper, platinum, and iron as raw materials have been extensively studied in the development of drug delivery systems, showing promising prospects for a range of anticancer purposes ( 12 ).…”

Section: Introductionsupporting

confidence: 63%

Cuproptosis scoring system to predict the clinical outcome and immune response in bladder cancer

et al. 2022

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Cuproptosis is a novel copper ion-dependent cell death type being regulated in cells, and this is quite different from the common cell death patterns such as apoptosis, pyroptosis, necroptosis, and ferroptosis. Interestingly, like with death patterns, cuproptosis-related genes have recently been reported to regulate the occurrence and progression of various tumors. However, in bladder cancer, the link between cuproptosis and clinical outcome, tumor microenvironment (TME) modification, and immunotherapy is unknown. To determine the role of cuprotosis in the tumor microenvironment, we systematically examined the characteristic patterns of 10 cuproptosis-related genes in bladder cancer (BLCA). By analyzing principal component data, we established a cuproptosis score to determine the degree of cuproptosis among patients. Finally, we evaluated the potential of these values in predicting BLCA prognosis and treatment responses. A comprehensive study of the mutations of cuproptosis-related genes in BLCA specimens was conducted at the genetic level, and their expression and survival patterns were evaluated using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Two cuproptosis patterns were constructed based on the transcription level of 10 cuproptosis-related genes, featuring differences in the prognosis and the infiltrating landscape of immune cells (especially T and dendritic cells) with interactions between cuproptosis and the TME. Our study further demonstrated that cuproptosis score may predict prognosis, immunophenotype sensitivity to chemotherapy, and immunotherapy response among bladder cancer patients. The development and progression of bladder cancer are likely to be influenced by cuproptosis, which may involve a diverse and complex TME. The cuproptosis pattern evaluated in our study may enhance understanding of immune infiltrations and guide more potent immunotherapy interventions.

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Section: Introductionsupporting

confidence: 63%

Cuproptosis scoring system to predict the clinical outcome and immune response in bladder cancer

et al. 2022

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“…Accumulating evidence have shown that the development of tumors is always related to programmed cell death (20-22). Bian Z et al constructed a cuproptosis-related prognostic gene signature in clear cell renal cell carcinoma, confirming the importance of cuproptosis in tumor development and progression (23). In-depth research in cuproptosis helps to facilitate new understandings of the pathogenesis of tumors.…”

Section: Discussionmentioning

confidence: 91%

Construction and validation of a cuproptosis-related lncRNA signature as a novel and robust prognostic model for colon adenocarcinoma

Wang

et al. 2022

Front. Oncol.

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BackgroundCuproptosis, a newly identified form of programmed cell death, is thought to play a role in tumorigenesis. Long non-coding RNAs (lncRNAs) are reported to be associated with tumor progression and prognosis in colon adenocarcinoma (COAD). However, the role and prognostic value of cuproptosis-related lncRNAs in COAD remains unknown. This study is devoted to constructing and validating a cuproptosis-related lncRNA signature that can predict COAD patient outcomes using bioinformatics methods.MethodsThe COAD mRNA and lncRNA expression profiles and corresponding clinical data were downloaded from The Cancer Genome Atlas (TCGA) database and 2,567 cuproptosis-related lncRNAs were obtained. A 10 cuproptosis-related-lncRNA prognostic signature was then constructed using the least absolute shrinkage and selection operator (LASSO) algorithm and Cox regression model and patients were divided into high- and low-risk groups. Kaplan-Meier analysis, receiver operating characteristic (ROC) curve, and a nomogram were employed to evaluate the predictive power of the signature. The immune characteristics and drug sensitivity were also investigated based on the signature. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to verify the risk model. In vitro experiments were conducted to validate the expression of the ten lncRNAs during cuproptosis.ResultsThe high-risk group was associated with shorter overall survival (OS) time in COAD patients (p<0.001). Multivariate Cox regression indicated that a high-risk score was an independent risk factor for poor prognosis (p<0.001). ROC curve analysis was performed to confirm the validity of the signature (area under the curve (AUC) at 3 years: 0.879). Gene Ontology (GO) enrichment analysis revealed that the signature was highly correlated with the immune response in biological processes. The immune function, the score of the immune cells, and the expression of immune checkpoints were significantly different between the two risk groups. Three drugs, LAQ824, FH535, YM155, were found to be more sensitive in the high-risk group. Finally, the expression levels of the ten lncRNAs comprising the signature were tested by qRT-PCR.ConclusionA ten-cuproptosis-related lncRNA signature was constructed that provided promising insights into personalized prognosis and drug selection among COAD patients.

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“…Cuproptosis a novel form of copper-induced cell death has been reported to be regulated by 16 mRNAs as described above. Besides, previous study has constructed prognostic signature using cuproptosis related mRNA based on TCGA-KIRC cohort (12). The AUC of 1-year, 3-year, and 5-year survival for ccRCC patients in their study was 0.652, 0.633, and 0.658, respectively.…”

Section: Discussionmentioning

confidence: 94%

“…Studies have constructed the signatures with cuproptosis related mRNAs (12) or lncRNAs (13) to predict the prognosis of ccRCC patients basing on the TCGA-KIRC cohort only. However, the prognostic value of signature constructed with CRLM for ccRCC patients has not been reported before.…”

Section: Introductionmentioning

confidence: 99%

Construction of a Cuproptosis-Related Signature for Predicting Prognosis and Immune Response in Clear Cell Renal Cell Carcinoma

Cui

Zhang²,

Shen

et al. 2022

Preprint

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Background Cuproptosis is a new form of programmed cell death which induced by copper. The signature of cuproptosis related lncRNAs and mRNAs (CRLM) has not been reported before in clear cell renal cell carcinoma. Methods The RNA-seq, clinical data, and single nucleotide variants (SNV) data of clear cell renal cell carcinoma (ccRCC) were obtained from the Cancer Genome Atlas (TCGA). Cuproptosis related long non-coding RNAs (lncRNAs) were identified via Pearson’s test. Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses were used to further screen prognosis related lncRNAs and mRNAs for signature construction. Cases were then randomly divided into training and testing set groups at ratio 1:1 to validate the cuproptosis signature. Kaplan–Meier survival analysis, receiver operating characteristic (ROC) curve analysis, nomogram, principal components analysis (PCA), gene set enrichment analyses (GSEA), mutation landscape, and therapies response were subsequently conducted with R or perl algorithms. A Japanese ccRCC cohort (n = 98) was used to validate this signature. Results A total of 245 lncRNAs were identified as cuproptosis related. Three of them (AL731577.2, LINC00460, AL133215.2) and cuproptosis related mRNA DBT were finally incorporated into the signature construction. High-risk group patients suffered from lower survival rate. The area under curve (AUC) of the novel signature for 1-, 3-, 5-year survival rates was 0.731, 0.718, 0.745, respectively. The concordance index (C-index) was 0.692. The Japanese cohort showed a good consistence with the results derived from the TCGA dataset. Tumor mutation burden (TMB) was also found to be a risking factor for ccRCC patients. Immune related Gene ontology terms were significantly enriched in high-risk patients. Besides, low-risk patients may be more sensitive to immune check inhibitors (ICIs), Sunitinib, and Pazopanib. High-risk patients may be more sensitive to Sorafenib. Conclusion The cuproptosis related signature is a promising and potential prognostic tool in predicting the survival of patients with ccRCC. It could contribute to precise and individualized ccRCC treatment.

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A Novel Cuproptosis-Related Prognostic Gene Signature and Validation of Differential Expression in Clear Cell Renal Cell Carcinoma

Cited by 241 publications

References 49 publications

Cuproptosis scoring system to predict the clinical outcome and immune response in bladder cancer

Cuproptosis scoring system to predict the clinical outcome and immune response in bladder cancer

Construction and validation of a cuproptosis-related lncRNA signature as a novel and robust prognostic model for colon adenocarcinoma

Construction of a Cuproptosis-Related Signature for Predicting Prognosis and Immune Response in Clear Cell Renal Cell Carcinoma

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