Objective:To identify chromatin regulators(CRs)-based molecular subtypes and risk scores for accurately predicting biochemical recurrence(BCR)after radical prostatectomy(RAP)in prostate cancer(PCa)patients.Methods:Dif...Objective:To identify chromatin regulators(CRs)-based molecular subtypes and risk scores for accurately predicting biochemical recurrence(BCR)after radical prostatectomy(RAP)in prostate cancer(PCa)patients.Methods:Differentially expressed genes(DEGs)between tumor and normal samples from The Cancer Genome Atlas(TCGA)and gene expression omnibus(GEO)databases were intersected with CR-related and prognostic genes.Consensus clustering,risk score analysis,functional analysis,immune microenvironment,m6A,and heterogeneity assessments were performed using R software.In vitro validation used DU145 and C42B PCa cell lines.Topoisomerase II alpha(TOP2A)was knocked down via si RNA.Assays included CCK-8 proliferation,colony formation,transwell migration/invasion,wound healing,and western blotting(WB)for pathway validation.Results:TOP2A and peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PPARGC1A)defined molecular subtypes and a risk score in TCGA,validated in a GEO dataset.Cluster 2 exhibited significantly shorter BCR-free survival vs.cluster 1 in TCGA[hazard ratio(HR):2.21;95%confidence interval(95%CI):1.32-3.73;P=0.003],GEO(HR:2.05;95%CI:1.05-4.02;P=0.010),and MSKCC2010(HR:5.93;95%CI:1.96-17.87;P<0.001).Similar survival differences were observed between high-and low-risk groups(defined by the median risk score).Cluster 2 showed greater tumor heterogeneity and higher m6A gene expression.Gene set variation analysis(GSVA)revealed downregulated cell-cycle pathways in cluster 2,alongside suppressed tumor-infiltrating immune cells.TOP2A knockdown significantly impaired PCa cell proliferation,colony formation,migration,and invasion.Mechanistically,it suppressed phosphoinositide 3-kinase(PI3K)/AKT serine/threonine kinase(AKT)pathway activation,reducing phosphorylated PI3K and AKT levels without altering total protein.Conclusions:TOP2A and PPARGC1A effectively stratify PCa subtypes for RAP patients.TOP2A drives malignant progression via the PI3K/AKT pathway.展开更多
Objective: The interplay between chemokine C-X-C motif ligand 12(CXCL12) and its specific receptors is known to trigger various signaling pathways, contributing to tumor proliferation and metastasis. Consequently,targ...Objective: The interplay between chemokine C-X-C motif ligand 12(CXCL12) and its specific receptors is known to trigger various signaling pathways, contributing to tumor proliferation and metastasis. Consequently,targeting this signaling axis has emerged as a potential strategy in cancer therapy. However, the precise role of CXCL12 in clinical therapy, especially in immunotherapy for bladder cancer(BCa), remains poorly elucidated.Methods: We gathered multiple omics data from public databases to unveil the clinical relevance and tumor immune landscape associated with CXCL12 in BCa patients. Univariate and multivariate Cox regression analyses were employed to assess the independent prognostic significance of CXCL12 expression and formulate a nomogram. The expression of CXCL12 in BCa cell lines and clinical tissue samples was validated using enzymelinked immunosorbent assays(ELISA) and immunohistochemistry(IHC).Results: While transcriptional expression of CXCL12 exhibited a decrease in nearly all tumor tissues, CXCL12 methylation expression was notably increased in BCa tissues. Single-cell RNA analysis highlighted tissue stem cells and endothelial cells as the primary sources expressing CXCL12. Abnormal CXCL12 expression, based on transcriptional and methylation levels, correlated with various clinical characteristics in BCa patients. Functional analysis indicated enrichment of CXCL12 and its co-expression genes in immune regulation and cell adhesion. The immune landscape analysis unveiled a significant association between CXCL12 expression and M2 macrophages(CD163~+ cells) in BCa tissues. Notably, CXCL12 expression emerged as a potential predictor of immunotherapy response and chemotherapy drug sensitivity in BCa patients.Conclusions: Taken together, these findings suggest aberrant production of CXCL12 in BCa tissues,potentially influencing the treatment responses of affected individuals.展开更多
Aging and circadian rhythms have been connected for decades,but their molecular interaction has remained unknown,especially for cancers.In this situation,we summarized the current research actuality and problems in th...Aging and circadian rhythms have been connected for decades,but their molecular interaction has remained unknown,especially for cancers.In this situation,we summarized the current research actuality and problems in this field using the bibliometric analysis.Publications in the PubMed and Web of Science databases were retrieved.Overall,there is a rising trend in the publication volume regarding aging and circadian rhythms in the field of cancer.Researchers from USA,Germany,Italy,China and England have greater studies than others.Top three publication institutions are University of California System,UDICE-French Research Universities and University of Texas System.Current research hotspots include oxidative stress,breast cancer,melatonin,cell cycle,calorie restriction,prostate cancer and NF-κB.In conclusion,results generated by bibliometric analysis indicate that many approaches involve in the complex interactions between aging and circadian rhythm in cancer.These established and emerging research directions guide our exploration of the regulatory mechanisms of aging and circadian rhythms in cancer and provide a reference for developing new research avenues.展开更多
The incre asing interest in RNA modifications has signifcantly advanced epigenomic and epitranscriptomic technologies.This study focuses on the immuno oncological impact of ALYREF in human cancer through a pan-cancer ...The incre asing interest in RNA modifications has signifcantly advanced epigenomic and epitranscriptomic technologies.This study focuses on the immuno oncological impact of ALYREF in human cancer through a pan-cancer analysis,enhancing understanding of this gene's role in cancer.We observed differential ALYREF expression between tumor and normal samples,correl ating strongly with prognosis in various cancers,particularly kidney renal papillary cell carcinoma(KIRP)and liver hepatocellular carcinoma(LIHC).ALYREF showed a negative correlation with most tumor-infitrating cells in lung squamous cell carcinoma(LUSC)and lymphoid neoplasm difuse large B-cell lymphoma(DLBC),while positive correlations were noted in IIHC,kidney chromophobe(KICH),mesothelioma(MESO),KIRP,pheochromocytoma and paraganglioma(PARD),and glioma(GBMLGG).Aditionally,ALYREF expression was closely associated with tumor heterogeneity,stemness indices,and a high mutation rate in TP53 across these cancers.In conclusion,ALYREF may serve as an oncogenic biomarker in numerous cancers,meriting further research attention.展开更多
Introduction Newborns typically acquire microbiota from both their mothers and the surrounding environment,which can eventually reach around 500 g in adulthood(1).Microbiota serves as a historical record of an individ...Introduction Newborns typically acquire microbiota from both their mothers and the surrounding environment,which can eventually reach around 500 g in adulthood(1).Microbiota serves as a historical record of an individual’s life and may also hold a predictive value for their future health(2).Human microbiota is involved in disease occurrence and progression(3,4).展开更多
The intricate relationship between cancer,circadian rhythms,and aging is increasingly recognized as a critical factor in understanding the mechanisms underlying tumorigenesis and cancer progression.Aging is a well-est...The intricate relationship between cancer,circadian rhythms,and aging is increasingly recognized as a critical factor in understanding the mechanisms underlying tumorigenesis and cancer progression.Aging is a well-established primary risk factor for cancer,while disruptions in circadian rhythms are intricately associated with the tumorigenesis and progression of various tumors.Moreover,aging itself disrupts circadian rhythms,leading to physiological changes that may accelerate cancer development.Despite these connections,the specific interplay between these processes and their collective impact on cancer remains inadequately explored in the literature.In this review,we systematically explore the physiological mechanisms of circadian rhythms and their influence on cancer development.We discuss how core circadian genes impact tumor risk and prognosis,highlighting the shared hallmarks of cancer and aging such as genomic instability,cellular senescence,and chronic inflammation.Furthermore,we examine the interplay between circadian rhythms and aging,focusing on how this crosstalk contributes to tumorigenesis,tumor proliferation,and apoptosis,as well as the impact on cellular metabolism and genomic stability.By elucidating the common pathways linking aging,circadian rhythms,and cancer,this review provides new insights into the pathophysiology of cancer and identifies potential therapeutic strategies.We propose that targeting the circadian regulation of cancer hallmarks could pave the way for novel treatments,including chronotherapy and antiaging interventions,which may offer important benefits in the clinical management of cancer.展开更多
Prostate cancer is the most prevalent malignant tumor among men,ranking first in incidence and second in mortality globally.Novel hormone therapies(NHT)targeting the androgen receptor(AR)pathway have become the standa...Prostate cancer is the most prevalent malignant tumor among men,ranking first in incidence and second in mortality globally.Novel hormone therapies(NHT)targeting the androgen receptor(AR)pathway have become the standard of care for metastatic prostate cancer.This review offers a comprehensive overview of NHT,including abiraterone,enzalutamide,apalutamide,darolutamide,and rezvilutamide,which have demonstrated efficacy in delaying disease progression and improving patient survival and quality of life.Nevertheless,resistance to NHT remains a critical challenge.The mechanisms underlying resistance are complex,involving AR gene amplification,mutations,splice variants,increased intratumoral androgens,and AR-independent pathways such as the glucocorticoid receptor,neuroendocrine differentiation,DNA repair defects,autophagy,immune evasion,and activation of alternative signaling pathways.This review discusses these resistance mechanisms and examines strategies to counteract them,including sequential treatment with novel AR-targeted drugs,chemotherapy,poly ADP-ribose polymerase inhibitors,radionuclide therapy,bipolar androgen therapy,and approaches targeting specific resistance pathways.Future research should prioritize elucidating the molecular basis of NHT resistance,optimizing existing therapeutic strategies,and developing more effective combination regimens.Additionally,advanced sequencing technologies and resistance research models should be leveraged to identify novel therapeutic targets and improve drug delivery efficiencies.These advancements hold the potential to overcome NHT resistance and significantly enhance the management and prognosis of patients with advanced prostate cancer.展开更多
The circadian clock is an internal timekeeper system that regulates biological processes through a central circadian clock and peripheral clocks controlling various genes.Basic helix-loop-helix ARNT-like 1(BMAL 1),als...The circadian clock is an internal timekeeper system that regulates biological processes through a central circadian clock and peripheral clocks controlling various genes.Basic helix-loop-helix ARNT-like 1(BMAL 1),also known as aryl hydrocarbon receptor nuclear translocator-like protein 1(ARNTL1),is a key component of the circadian clock.The deletion of BMAL1 alone can abolish the circadian rhythms of the human body.BMAL 1 plays a critical role in immune cell function.Dysregulation of BMAL 1 is linked to immune-related diseases such as autoimmune diseases,infectious diseases,and cancer,and vice versa.This review highlights the significant role of BMAL 1 in governing immune cells,including their development,differentiation,migration,homing,metabolism,and effector functions.This study also explores how dysregulation of BMAL1 can have far-reaching implications and potentially contribute to the onset of immune-related diseases such as autoimmune diseases,infectious diseases,cancer,sepsis,and trauma.Furthermore,this review discusses treatments for immune-related diseases that target BMAL 1 disorders.Understanding the impact of BMAL 1 on immune function can provide insights into the pathogenesis of immune-related diseases and help in the development of more effective treatment strategies.Targeting BMAL 1 has been demonstrated to achieve good efficacy in immune-related diseases,indicating its promising potential as a targetable therapeutic target in these diseases.展开更多
基金supported by the funding of Chinese Scholarship Council(No.202206240086)。
文摘Objective:To identify chromatin regulators(CRs)-based molecular subtypes and risk scores for accurately predicting biochemical recurrence(BCR)after radical prostatectomy(RAP)in prostate cancer(PCa)patients.Methods:Differentially expressed genes(DEGs)between tumor and normal samples from The Cancer Genome Atlas(TCGA)and gene expression omnibus(GEO)databases were intersected with CR-related and prognostic genes.Consensus clustering,risk score analysis,functional analysis,immune microenvironment,m6A,and heterogeneity assessments were performed using R software.In vitro validation used DU145 and C42B PCa cell lines.Topoisomerase II alpha(TOP2A)was knocked down via si RNA.Assays included CCK-8 proliferation,colony formation,transwell migration/invasion,wound healing,and western blotting(WB)for pathway validation.Results:TOP2A and peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PPARGC1A)defined molecular subtypes and a risk score in TCGA,validated in a GEO dataset.Cluster 2 exhibited significantly shorter BCR-free survival vs.cluster 1 in TCGA[hazard ratio(HR):2.21;95%confidence interval(95%CI):1.32-3.73;P=0.003],GEO(HR:2.05;95%CI:1.05-4.02;P=0.010),and MSKCC2010(HR:5.93;95%CI:1.96-17.87;P<0.001).Similar survival differences were observed between high-and low-risk groups(defined by the median risk score).Cluster 2 showed greater tumor heterogeneity and higher m6A gene expression.Gene set variation analysis(GSVA)revealed downregulated cell-cycle pathways in cluster 2,alongside suppressed tumor-infiltrating immune cells.TOP2A knockdown significantly impaired PCa cell proliferation,colony formation,migration,and invasion.Mechanistically,it suppressed phosphoinositide 3-kinase(PI3K)/AKT serine/threonine kinase(AKT)pathway activation,reducing phosphorylated PI3K and AKT levels without altering total protein.Conclusions:TOP2A and PPARGC1A effectively stratify PCa subtypes for RAP patients.TOP2A drives malignant progression via the PI3K/AKT pathway.
基金supported by the Research fund of Anhui Institute of Translational Medicine (No. 2021zhyx-C62)。
文摘Objective: The interplay between chemokine C-X-C motif ligand 12(CXCL12) and its specific receptors is known to trigger various signaling pathways, contributing to tumor proliferation and metastasis. Consequently,targeting this signaling axis has emerged as a potential strategy in cancer therapy. However, the precise role of CXCL12 in clinical therapy, especially in immunotherapy for bladder cancer(BCa), remains poorly elucidated.Methods: We gathered multiple omics data from public databases to unveil the clinical relevance and tumor immune landscape associated with CXCL12 in BCa patients. Univariate and multivariate Cox regression analyses were employed to assess the independent prognostic significance of CXCL12 expression and formulate a nomogram. The expression of CXCL12 in BCa cell lines and clinical tissue samples was validated using enzymelinked immunosorbent assays(ELISA) and immunohistochemistry(IHC).Results: While transcriptional expression of CXCL12 exhibited a decrease in nearly all tumor tissues, CXCL12 methylation expression was notably increased in BCa tissues. Single-cell RNA analysis highlighted tissue stem cells and endothelial cells as the primary sources expressing CXCL12. Abnormal CXCL12 expression, based on transcriptional and methylation levels, correlated with various clinical characteristics in BCa patients. Functional analysis indicated enrichment of CXCL12 and its co-expression genes in immune regulation and cell adhesion. The immune landscape analysis unveiled a significant association between CXCL12 expression and M2 macrophages(CD163~+ cells) in BCa tissues. Notably, CXCL12 expression emerged as a potential predictor of immunotherapy response and chemotherapy drug sensitivity in BCa patients.Conclusions: Taken together, these findings suggest aberrant production of CXCL12 in BCa tissues,potentially influencing the treatment responses of affected individuals.
基金supported by the Chinese Scholarship Council(No.202206240086)Zhejiang Province Public Welfare Technology Application Research Project in China(No.TGY23H160090 and No.LGF21H160029)+1 种基金Taizhou Science and Technology Project,Zhejiang Province(No.20ywb12)Program for Talents of Chongqing University Three Gorges Hospital(No.2022YJKYXM-036).
文摘Aging and circadian rhythms have been connected for decades,but their molecular interaction has remained unknown,especially for cancers.In this situation,we summarized the current research actuality and problems in this field using the bibliometric analysis.Publications in the PubMed and Web of Science databases were retrieved.Overall,there is a rising trend in the publication volume regarding aging and circadian rhythms in the field of cancer.Researchers from USA,Germany,Italy,China and England have greater studies than others.Top three publication institutions are University of California System,UDICE-French Research Universities and University of Texas System.Current research hotspots include oxidative stress,breast cancer,melatonin,cell cycle,calorie restriction,prostate cancer and NF-κB.In conclusion,results generated by bibliometric analysis indicate that many approaches involve in the complex interactions between aging and circadian rhythm in cancer.These established and emerging research directions guide our exploration of the regulatory mechanisms of aging and circadian rhythms in cancer and provide a reference for developing new research avenues.
基金the Chinese Scholarship Council(Grant No.202206240086)the National Natural Science Foundation of China(Grant No.82170432)programs from Science and Technology Department of Sichuan Province(Grant No.2020YFSY0024).
文摘The incre asing interest in RNA modifications has signifcantly advanced epigenomic and epitranscriptomic technologies.This study focuses on the immuno oncological impact of ALYREF in human cancer through a pan-cancer analysis,enhancing understanding of this gene's role in cancer.We observed differential ALYREF expression between tumor and normal samples,correl ating strongly with prognosis in various cancers,particularly kidney renal papillary cell carcinoma(KIRP)and liver hepatocellular carcinoma(LIHC).ALYREF showed a negative correlation with most tumor-infitrating cells in lung squamous cell carcinoma(LUSC)and lymphoid neoplasm difuse large B-cell lymphoma(DLBC),while positive correlations were noted in IIHC,kidney chromophobe(KICH),mesothelioma(MESO),KIRP,pheochromocytoma and paraganglioma(PARD),and glioma(GBMLGG).Aditionally,ALYREF expression was closely associated with tumor heterogeneity,stemness indices,and a high mutation rate in TP53 across these cancers.In conclusion,ALYREF may serve as an oncogenic biomarker in numerous cancers,meriting further research attention.
基金supported by Chinese Scholarship Council(No.202206240086)。
文摘Introduction Newborns typically acquire microbiota from both their mothers and the surrounding environment,which can eventually reach around 500 g in adulthood(1).Microbiota serves as a historical record of an individual’s life and may also hold a predictive value for their future health(2).Human microbiota is involved in disease occurrence and progression(3,4).
基金supported by the Chinese Scholarship Council(grant no.202206240086)a regional innovation cooperation project of Sichuan Province(grant no.23QYCX0136)。
文摘The intricate relationship between cancer,circadian rhythms,and aging is increasingly recognized as a critical factor in understanding the mechanisms underlying tumorigenesis and cancer progression.Aging is a well-established primary risk factor for cancer,while disruptions in circadian rhythms are intricately associated with the tumorigenesis and progression of various tumors.Moreover,aging itself disrupts circadian rhythms,leading to physiological changes that may accelerate cancer development.Despite these connections,the specific interplay between these processes and their collective impact on cancer remains inadequately explored in the literature.In this review,we systematically explore the physiological mechanisms of circadian rhythms and their influence on cancer development.We discuss how core circadian genes impact tumor risk and prognosis,highlighting the shared hallmarks of cancer and aging such as genomic instability,cellular senescence,and chronic inflammation.Furthermore,we examine the interplay between circadian rhythms and aging,focusing on how this crosstalk contributes to tumorigenesis,tumor proliferation,and apoptosis,as well as the impact on cellular metabolism and genomic stability.By elucidating the common pathways linking aging,circadian rhythms,and cancer,this review provides new insights into the pathophysiology of cancer and identifies potential therapeutic strategies.We propose that targeting the circadian regulation of cancer hallmarks could pave the way for novel treatments,including chronotherapy and antiaging interventions,which may offer important benefits in the clinical management of cancer.
文摘Prostate cancer is the most prevalent malignant tumor among men,ranking first in incidence and second in mortality globally.Novel hormone therapies(NHT)targeting the androgen receptor(AR)pathway have become the standard of care for metastatic prostate cancer.This review offers a comprehensive overview of NHT,including abiraterone,enzalutamide,apalutamide,darolutamide,and rezvilutamide,which have demonstrated efficacy in delaying disease progression and improving patient survival and quality of life.Nevertheless,resistance to NHT remains a critical challenge.The mechanisms underlying resistance are complex,involving AR gene amplification,mutations,splice variants,increased intratumoral androgens,and AR-independent pathways such as the glucocorticoid receptor,neuroendocrine differentiation,DNA repair defects,autophagy,immune evasion,and activation of alternative signaling pathways.This review discusses these resistance mechanisms and examines strategies to counteract them,including sequential treatment with novel AR-targeted drugs,chemotherapy,poly ADP-ribose polymerase inhibitors,radionuclide therapy,bipolar androgen therapy,and approaches targeting specific resistance pathways.Future research should prioritize elucidating the molecular basis of NHT resistance,optimizing existing therapeutic strategies,and developing more effective combination regimens.Additionally,advanced sequencing technologies and resistance research models should be leveraged to identify novel therapeutic targets and improve drug delivery efficiencies.These advancements hold the potential to overcome NHT resistance and significantly enhance the management and prognosis of patients with advanced prostate cancer.
文摘The circadian clock is an internal timekeeper system that regulates biological processes through a central circadian clock and peripheral clocks controlling various genes.Basic helix-loop-helix ARNT-like 1(BMAL 1),also known as aryl hydrocarbon receptor nuclear translocator-like protein 1(ARNTL1),is a key component of the circadian clock.The deletion of BMAL1 alone can abolish the circadian rhythms of the human body.BMAL 1 plays a critical role in immune cell function.Dysregulation of BMAL 1 is linked to immune-related diseases such as autoimmune diseases,infectious diseases,and cancer,and vice versa.This review highlights the significant role of BMAL 1 in governing immune cells,including their development,differentiation,migration,homing,metabolism,and effector functions.This study also explores how dysregulation of BMAL1 can have far-reaching implications and potentially contribute to the onset of immune-related diseases such as autoimmune diseases,infectious diseases,cancer,sepsis,and trauma.Furthermore,this review discusses treatments for immune-related diseases that target BMAL 1 disorders.Understanding the impact of BMAL 1 on immune function can provide insights into the pathogenesis of immune-related diseases and help in the development of more effective treatment strategies.Targeting BMAL 1 has been demonstrated to achieve good efficacy in immune-related diseases,indicating its promising potential as a targetable therapeutic target in these diseases.
