The Dysregulation of Inflammatory Pathways Triggered by Copper Exposure

Deng, Huidan; Zhu, Song; Yang, Huiru; Cui, Hengmin; Guo, Hongrui; Deng, Junliang; Ren, Zhihua; Geng, Yi; Ouyang, Ping; Xu, Zhiwen; Deng, Youtian; Zhu, Yanqiu

doi:10.1007/s12011-022-03171-0

Cited by 37 publications

(28 citation statements)

References 101 publications

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“…Cuproptosis-Related Genes. Tsvetkov et al, Deng et al, and Emami et al proposed key genes involved in the tumor copper death mechanism, including ATP7A, ATP7B, CDKN2A, DBT, DLAT, DLD, DLST, FDX1, GCSH, GLS, LIAS, LIPT1, LIPT2, MTF1, NFE2L2, NLRP3, PDHA1, PDHB, and SLC31A1 [7,11,12]. The cuproptosis-related genes coexpressed with cuproptosis genes were obtained based on TCGA-PAAD samples.…”

Section: Identification Ofmentioning

confidence: 99%

A Novel Cuproptosis‐Associated Gene Signature to Predict Prognosis in Patients with Pancreatic Cancer

Jiang

Hou

et al. 2023

BioMed Research International

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Background. Pancreatic cancer (PAAD) is a malignant tumor with a poor prognosis and lacks sensitive biomarkers for diagnosis and targeted therapy. Cuproptosis, a recently proposed form of cell death based on cellular copper ion concentration, plays a key role in cancer biology. This study is aimed at constructing a risk model for predicting the prognosis of PAAD patients based on cuproptosis-related genes. Methods. Pancreatic-related data from UCSC-TCGA and UCSC-GTEx databases were extracted for analysis, and TCGA-PAAD samples were randomly divided into the training and validation groups. Pearson correlation analysis was used to obtain cuproptosis-related genes coexpressed with 19 copper death genes. Univariate Cox and Lasso regression analyses were used to obtain cuproptosis-related prognostic genes. Multivariate Cox regression analysis was used to construct the final prognostic risk model. The risk score curve, Kaplan-Meier survival curves, and ROC curve were used to evaluate the predictive ability of the Cox risk model. Finally, the functional annotation of the risk model was obtained through enrichment analysis. Results. The Cox risk model has an eight prognostic cuproptosis-related gene signature. Kaplan-Meier survival curves demonstrated that the high-risk group had a shorter survival time. The ROC curve of the risk score was well created to predict one-, three-, and five-year survival rates, and AUC of the risk score was higher than other clinical characteristics. Cox regression analysis revealed that the risk score has an independent prognostic value for PAAD. GSEA reveals specific tumor pathways associated with the risk model (Myc targets v1, mTORC1 signaling, and E2F targets). Conclusions. We constructed a prognostic model containing eight cuproptosis-related genes (AKR1B10, KLHL29, PROM2, PIP5K1C, KIF18B, AMIGO2, MRPL3, and PI4KB) that can accurately predict the prognosis of PAAD patients. The results will provide new perspectives for individualized outcome prediction and new therapy development for PAAD patients.

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Section: Identification Ofmentioning

confidence: 99%

A Novel Cuproptosis‐Associated Gene Signature to Predict Prognosis in Patients with Pancreatic Cancer

Jiang

Hou

et al. 2023

BioMed Research International

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“…A copper deficiency stops cell proliferation and spreading, but exceeding cellular needs will damage cell membranes, proteins, and nucleic acids [52]. This excessive copper will induce cyclins and cyclin-dependent kinase (CDK)-2 in intracellular cells [59]. Thus, copper deficiency and excess cause the copper-transporting Ptype ATPase (ATP)-7A and ATP7B gene mutations, resulting in Menkes' and Wilson's diseases, respectively [60].…”

Section: Physiological Functions Of Copper and Zinc Elementsmentioning

confidence: 99%

Combining Copper and Zinc into a Biosensor for Anti-Chemoresistance and Achieving Osteosarcoma Therapeutic Efficacy

Zaidi¹,

Miskon²

2023

Preprint

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Due to its built-up chemoresistance after prolonged usage, the demand for replacing platinum in metal-based drugs (MBD) is rising. The first MBD approved by the FDA for cancer therapy was cisplatin in 1978. Even after nearly four and a half decades of trials, there has been no significant improvement in osteosarcoma (OS) therapy. In fact, many MBD have been developed, but the chemoresistance problem raised by platinum remains unresolved. This motivates us to elucidate the possibilities of the copper and zinc (CuZn) combination to replace platinum in MBD. Thus, the anti-chemoresistance properties of CuZn and their physiological functions for OS therapy are highlighted. Herein, we summarise their chelators, main organic solvents, and ligand functions in their structures that are involved in anti-chemoresistance properties. Through this review, it is rational to discuss their ligands’ roles as biosensors in drug delivery systems. Hereafter, an in-depth understanding of their redox and photoactive function relationships is provided. The disadvantage is that the other functions of biosensors cannot be elaborated on here. As a result, this review is being developed, which is expected to intensify OS drugs with higher cure rates. Nonetheless, this advancement intends to solve the major chemoresistance obstacle towards clinical efficacy.

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“…The Perl language was used to convert the form of data expression (Ensembl ID transformation to Gene Symbol) of the samples and distinguish between mRNA and lncRNA in every sample. The cuproptosis-related genes were identified from three studies [6,14,15]. The result files of various immune cell infiltration calculated with different algorithms were downloaded from the Tumor Immune Estimation Resource 2.0 database (TIMER2.0, http://timer.compgenomics.org/).…”

Section: Acquisition and Processing Of Datasetsmentioning

confidence: 99%

A cuproptosis-related lncRNA signature for predicting prognosis and immune response in hepatocellular carcinoma

Yao

Jia

et al. 2022

Preprint

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Background: Hepatocellular carcinoma (HCC) has a high incidence and poor prognosis. Cuproptosis is a novel type of cell death, which differs from previously reported types of cell death such as apoptosis, autophagy, proptosis, ferroptosis, necroptosis, etc. Long non-coding RNAs (lncRNAs) play multiple roles in HCC. To improve the prognosis of HCC, it is necessary to construct a signature using cuproptosis-related lncRNAs. Methods: We downloaded information including RNA-seq transcriptome, clinical data and simple nucleotide variation data from The Cancer Genome Atlas (TCGA) database, and obtained cuproptosis-related genes from published studies. The cuproptosis-related lncRNAs were obtained by correlation analysis, and subsequently used to construct a prognostic cuproptosis-related lncRNA signature. Analyses of overall survival (OS) and progression-free survival (PFS) were used to evaluate prognostic validity. The receiver operating characteristic (ROC) curve with the area under the curve (AUC) values and the index of concordance (c-index) curve were drawn to evaluate the accuracy of the signature. The tumor microenvironment (TME) was analyzed by ESTIMATE algorithm. The immune cell data with various algorithms was downloaded from the Tumor Immune Estimation Resource (TIMER) 2.0 database. Immune-related pathways were analyzed by single-sample gene set enrichment analysis (ssGSEA) algorithm. Immunophenoscore (IPS) scores from The Cancer Immunome (TCIA) database were used to evaluate immunotherapy response. The "pRRophetic" R package was employed to screen drugs for high-risk patients. Results: We constructed a cuproptosis-related lncRNA signature containing 11 lncRNAs: AC125437.1, PCED1B-AS1, PICSAR, AP001372.2, AC027097.1, LINC00479, and SLC6A1-AS1 to predict the prognosis of HCC patients. This signature had excellent accuracy, and was independent of the stratification of clinicopathological features. Further study showed that high-risk tumors under this signature had higher TMB, fewer TME components and higher tumor purity. The immune-related analysis showed that the tumors with high risk were not enriched in immune cell infiltration or immune process pathways, and high-risk patients had a poor response to immunotherapy. Finally, 29 drugs such as sorafenib, dasatinib and paclitaxel were screened for high-risk HCC patients to improve their prognosis. Conclusion: Our prognostic cuproptosis-related lncRNA signature was accurate and effective for predicting the prognosis of HCC. The immunotherapy was unsuitable for high-risk HCC patients with this signature.

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The Dysregulation of Inflammatory Pathways Triggered by Copper Exposure

Cited by 37 publications

References 101 publications

A Novel Cuproptosis‐Associated Gene Signature to Predict Prognosis in Patients with Pancreatic Cancer

A Novel Cuproptosis‐Associated Gene Signature to Predict Prognosis in Patients with Pancreatic Cancer

Combining Copper and Zinc into a Biosensor for Anti-Chemoresistance and Achieving Osteosarcoma Therapeutic Efficacy

A cuproptosis-related lncRNA signature for predicting prognosis and immune response in hepatocellular carcinoma

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