Background:Cuprotosis is a newly discovered Copper-dependence form of cell death.Cuprotosis-related genes(CRGs)regulating mitochondrial metabolism and protein lipoylation suggest the critical roles cuprotosis for in c...Background:Cuprotosis is a newly discovered Copper-dependence form of cell death.Cuprotosis-related genes(CRGs)regulating mitochondrial metabolism and protein lipoylation suggest the critical roles cuprotosis for in cancer.However,the prognostic value of CRGs in the highly immunogenic cancer type,kidney renal clear cell carcinoma(KIRC)needs to be further studied.Herein,we aim to identify novel prognostic genes and construct a CRGs prognostic signature for KIRC.Methods:We downloaded the mRNA sequencing data from the Cancer Genome Atlas,differentially expressed CRGs were screened out and their bio-function was elucidated.Then we used Cox regression analysis to establish a prediction model of CRGs.Subsequently,a prognostic scoring model based on the regression coefficients of the screened out CRGs and their corresponding mRNA expressions were constructed and validated.Results:Seven differentially expressed CRGs were screened.A two-gene model was built to separate samples into high-risk and low-risk groups.Overall survival was lower in the high-risk group than in the low-risk group(p<0.05).The receiver operating characteristic curve showed a good diagnostic efficiency of the signature.We verified this prognostic model in the Cancer Genome Atlas test cohorts.The risk score was identified as an independent prognostic factor via multivariate Cox regression.Moreover,the nomogram was used to predict 1-/3-/5-year OS of KIRC patients.Furthermore,risk score has a very significant effect on the infiltration of immune cells and the expression of immune checkpoints.Conclusions:To conclude,we constructed a novel prognostic signature based on CRGs.Targeting cuprotosis may represent a promising approach for the treatment of KIRC.展开更多
BACKGROUND The pyruvate dehydrogenase E1 subunitβ(PDHB)gene which regulates energy metabolism is located in mitochondria.However,few studies have elucidated the role and mechanism of PDHB in different cancers.AIM To ...BACKGROUND The pyruvate dehydrogenase E1 subunitβ(PDHB)gene which regulates energy metabolism is located in mitochondria.However,few studies have elucidated the role and mechanism of PDHB in different cancers.AIM To comprehensive pan-cancer analysis of PDHB was performed based on bioinformatics approaches to explore its tumor diagnostic and prognostic value and tumor immune relevance in cancer.In vitro experiments were performed to examine the biological regulation of PDHB in liver cancer.METHODS Pan-cancer data related to PDHB were obtained from the Cancer Genome Atlas(TCGA)database.Analysis of the gene expression profiles of PDHB was based on TCGA and Genotype Tissue Expression Dataset databases.Cox regression analysis and Kaplan-Meier methods were used to assess the correlation between PDHB expression and survival prognosis in cancer patients.The correlation between PDHB and receiver operating characteristic diagnostic curve,clinicopathological staging,somatic mutation,tumor mutation burden(TMB),microsatellite instability(MSI),DNA methylation,and drug susceptibility in pan-cancer was also analyzed.Various algorithms were used to analyze the correlation between PDHB and immune cell infiltration and tumor chemotaxis environment,as well as the co-expression analysis of PDHB and immune checkpoint(ICP)genes.The expression and functional phenotype of PDHB in single tumor cells were studied by single-cell sequencing,and the functional enrichment analysis of PDHB-related genes was performed.The study also validated the level of mRNA or protein expression of PDHB in several cancers.Finally,in vitro experiments verified the regulatory effect of PDHB on the proliferation,migration,and invasion of liver cancer.RESULTS PDHB was significantly and differently expressed in most cancers.PDHB was significantly associated with prognosis in patients with a wide range of cancers,including kidney renal clear cell carcinoma,kidney renal papillary cell carcinoma,breast invasive carcinoma,and brain lower grade glioma.In some cancers,PDHB expression was clearly associated with gene mutations,clinicopathological stages,and expression of TMB,MSI,and ICP genes.The expression of PDHB was closely related to the infiltration of multiple immune cells in the immune microenvironment and the regulation of tumor chemotaxis environment.In addition,single-cell sequencing results showed that PDHB correlated with different biological phenotypes of multiple cancer single cells.This study further demonstrated that down-regulation of PDHB expression inhibited the proliferation,migration,and invasion functions of hepatoma cells.CONCLUSION As a member of pan-cancer,PDHB may be a novel cancer marker with potential value in diagnosing cancer,predicting prognosis,and in targeted therapy.展开更多
Metals are essential components of both micronutrients and macronutrients in living organisms and are involved in a variety of immune processes in the forms of free ions or protein-coupled complexes(metalloproteins).M...Metals are essential components of both micronutrients and macronutrients in living organisms and are involved in a variety of immune processes in the forms of free ions or protein-coupled complexes(metalloproteins).Multiple aspects of the immune system,from the structural and functional control of immune-related proteins to the cellular responses to immunotherapy,could be affected by metals.Therefore,the employment of metal for the regulation of immunity,termed as metalloimmunology,is gaining interest as a prevalent and efficacious approach to combating cancer.However,the manipulation of metalloimmunology using traditional drugs presents several challenges,including limited bioavailability,adverse effects,and a lack of targeting specificity.This review provides an overview of the latest findings in metal and metal-regulatory therapeutic agents for the treatment of cancer.Essential trace metal elements,such as iron,zinc,copper,manganese,magnesium,and calcium,as well as heavy metal drugs and their mechanisms of action,will be discussed with a particular focus on their roles in regulating the tumor-immune interplay.The latest nanotechnology employed in the administration of metal-regulatory drugs and the design concepts for tailored therapeutic interventions will be discussed.These concepts and information offer promising clinical possibilities of modulating cancer immunology by targeting metal metabolism.展开更多
Copper(Cuprum)is an essential trace metal indispensable for the function of numerous enzymatic molecules implicated in cellular metabolism.Emerging evidence has demonstrated the role of copper in angiogenesis and cell...Copper(Cuprum)is an essential trace metal indispensable for the function of numerous enzymatic molecules implicated in cellular metabolism.Emerging evidence has demonstrated the role of copper in angiogenesis and cellular signaling.Moreover,raised copper levels have been detected in hepatocellular carcinoma and other cancers.An inherited or acquired copper imbalance,including inadequately low or excessively high copper levels,as well as inappropriate copper distribution in the body,is implicated in a number of diseases.In addition,a recent groundbreaking study identified a copperinduced type of programmed cell death named cuprotosis,the mechanism of which greatly deferred from that of other known cell death modes.The first part provides an overview of the regulation of copper homeostasis and discusses the underlying mechanisms of cuprotosis.In the second part,the authors focus on the functions of copper in liver diseases and other metabolic disorders,before discussing how this knowledge could contribute to the development of effective targets to treat such diseases.展开更多
基金financially supported by Hunan Provincial Natural Science Foundation of China 2022JJ40405(X.L).
文摘Background:Cuprotosis is a newly discovered Copper-dependence form of cell death.Cuprotosis-related genes(CRGs)regulating mitochondrial metabolism and protein lipoylation suggest the critical roles cuprotosis for in cancer.However,the prognostic value of CRGs in the highly immunogenic cancer type,kidney renal clear cell carcinoma(KIRC)needs to be further studied.Herein,we aim to identify novel prognostic genes and construct a CRGs prognostic signature for KIRC.Methods:We downloaded the mRNA sequencing data from the Cancer Genome Atlas,differentially expressed CRGs were screened out and their bio-function was elucidated.Then we used Cox regression analysis to establish a prediction model of CRGs.Subsequently,a prognostic scoring model based on the regression coefficients of the screened out CRGs and their corresponding mRNA expressions were constructed and validated.Results:Seven differentially expressed CRGs were screened.A two-gene model was built to separate samples into high-risk and low-risk groups.Overall survival was lower in the high-risk group than in the low-risk group(p<0.05).The receiver operating characteristic curve showed a good diagnostic efficiency of the signature.We verified this prognostic model in the Cancer Genome Atlas test cohorts.The risk score was identified as an independent prognostic factor via multivariate Cox regression.Moreover,the nomogram was used to predict 1-/3-/5-year OS of KIRC patients.Furthermore,risk score has a very significant effect on the infiltration of immune cells and the expression of immune checkpoints.Conclusions:To conclude,we constructed a novel prognostic signature based on CRGs.Targeting cuprotosis may represent a promising approach for the treatment of KIRC.
基金Supported by The 2021 Central-Guided Local Science and Technology Development FundLanzhou COVID-19 Prevention and Control Technology Research Project,No.2020-XG-1Gansu Province Outstanding Graduate Student"Innovation Star"Project,No.2022CXZX-748,No.2022CXZX-746.
文摘BACKGROUND The pyruvate dehydrogenase E1 subunitβ(PDHB)gene which regulates energy metabolism is located in mitochondria.However,few studies have elucidated the role and mechanism of PDHB in different cancers.AIM To comprehensive pan-cancer analysis of PDHB was performed based on bioinformatics approaches to explore its tumor diagnostic and prognostic value and tumor immune relevance in cancer.In vitro experiments were performed to examine the biological regulation of PDHB in liver cancer.METHODS Pan-cancer data related to PDHB were obtained from the Cancer Genome Atlas(TCGA)database.Analysis of the gene expression profiles of PDHB was based on TCGA and Genotype Tissue Expression Dataset databases.Cox regression analysis and Kaplan-Meier methods were used to assess the correlation between PDHB expression and survival prognosis in cancer patients.The correlation between PDHB and receiver operating characteristic diagnostic curve,clinicopathological staging,somatic mutation,tumor mutation burden(TMB),microsatellite instability(MSI),DNA methylation,and drug susceptibility in pan-cancer was also analyzed.Various algorithms were used to analyze the correlation between PDHB and immune cell infiltration and tumor chemotaxis environment,as well as the co-expression analysis of PDHB and immune checkpoint(ICP)genes.The expression and functional phenotype of PDHB in single tumor cells were studied by single-cell sequencing,and the functional enrichment analysis of PDHB-related genes was performed.The study also validated the level of mRNA or protein expression of PDHB in several cancers.Finally,in vitro experiments verified the regulatory effect of PDHB on the proliferation,migration,and invasion of liver cancer.RESULTS PDHB was significantly and differently expressed in most cancers.PDHB was significantly associated with prognosis in patients with a wide range of cancers,including kidney renal clear cell carcinoma,kidney renal papillary cell carcinoma,breast invasive carcinoma,and brain lower grade glioma.In some cancers,PDHB expression was clearly associated with gene mutations,clinicopathological stages,and expression of TMB,MSI,and ICP genes.The expression of PDHB was closely related to the infiltration of multiple immune cells in the immune microenvironment and the regulation of tumor chemotaxis environment.In addition,single-cell sequencing results showed that PDHB correlated with different biological phenotypes of multiple cancer single cells.This study further demonstrated that down-regulation of PDHB expression inhibited the proliferation,migration,and invasion functions of hepatoma cells.CONCLUSION As a member of pan-cancer,PDHB may be a novel cancer marker with potential value in diagnosing cancer,predicting prognosis,and in targeted therapy.
基金supported by grants from the National Key R&D Program of China(Nos.2021YFA1201100,and 2022YFA1206100)the National Natural Science Foundation of China(Nos.32271449,32201158,and 51773188)+2 种基金CAS Project for Young Scientists in Basic Research(No.YSBR-036)Key Project of Natural Science Foundation of Shandong Province(No.ZR2020KE016)Shandong Provincial Key Research and Development Program(Major Scientific and Technological Innovation Project,No.2022CXGC010505).
文摘Metals are essential components of both micronutrients and macronutrients in living organisms and are involved in a variety of immune processes in the forms of free ions or protein-coupled complexes(metalloproteins).Multiple aspects of the immune system,from the structural and functional control of immune-related proteins to the cellular responses to immunotherapy,could be affected by metals.Therefore,the employment of metal for the regulation of immunity,termed as metalloimmunology,is gaining interest as a prevalent and efficacious approach to combating cancer.However,the manipulation of metalloimmunology using traditional drugs presents several challenges,including limited bioavailability,adverse effects,and a lack of targeting specificity.This review provides an overview of the latest findings in metal and metal-regulatory therapeutic agents for the treatment of cancer.Essential trace metal elements,such as iron,zinc,copper,manganese,magnesium,and calcium,as well as heavy metal drugs and their mechanisms of action,will be discussed with a particular focus on their roles in regulating the tumor-immune interplay.The latest nanotechnology employed in the administration of metal-regulatory drugs and the design concepts for tailored therapeutic interventions will be discussed.These concepts and information offer promising clinical possibilities of modulating cancer immunology by targeting metal metabolism.
基金Talent Development Plan for Beijing High-level Public Health Technical Personnel Project,Grant/Award Number:2022-2-014。
文摘Copper(Cuprum)is an essential trace metal indispensable for the function of numerous enzymatic molecules implicated in cellular metabolism.Emerging evidence has demonstrated the role of copper in angiogenesis and cellular signaling.Moreover,raised copper levels have been detected in hepatocellular carcinoma and other cancers.An inherited or acquired copper imbalance,including inadequately low or excessively high copper levels,as well as inappropriate copper distribution in the body,is implicated in a number of diseases.In addition,a recent groundbreaking study identified a copperinduced type of programmed cell death named cuprotosis,the mechanism of which greatly deferred from that of other known cell death modes.The first part provides an overview of the regulation of copper homeostasis and discusses the underlying mechanisms of cuprotosis.In the second part,the authors focus on the functions of copper in liver diseases and other metabolic disorders,before discussing how this knowledge could contribute to the development of effective targets to treat such diseases.
