Background:Receptor-interacting protein kinases(RIPKs)regulate cell death,inflammation,and immune responses,yet their roles in cancer are not fully understood.This study investigates the expression,genomic alterations...Background:Receptor-interacting protein kinases(RIPKs)regulate cell death,inflammation,and immune responses,yet their roles in cancer are not fully understood.This study investigates the expression,genomic alterations,and functional implications of RIPK family members across various cancers.Methods:We collected multi-omics data from The Cancer Genome Atlas and other public databases,including gene expression,copy number variation(CNV),mutation,methylation,tumor mutation burden(TMB),and microsatellite instability(MSI).Differential expression and survival analyses were performed using DESeq2 and Cox proportional hazards models.CNV and mutation data were analyzed with GISTIC2 and Mutect2,and methylation data with the ChAMP package.Correlations with TMB and MSI were assessed using Pearson coefficients,and gene set enrichment analysis was conducted with the MSigDB Hallmark gene sets.Results:RIPK family members show significant differential expression in various cancers,with RIPK1 and RIPK4 frequently altered.Survival analysis reveals heterogeneous impacts on overall survival.CNV and mutation analyses identify high alteration frequencies for RIPK2 and RIPK7,affecting gene expression.RIPK1 and RIPK7 are hypermethylated in several cancers,inversely correlating with RIPK3 expression.RIPK1,RIPK2,RIPK5,RIPK6,and RIPK7 correlate positively with TMB,while RIPK3 shows negative correlations in some cancers.MSI analysis indicates associations with DNA mismatch repair.G ene set enrichment analysis highlights immune-related pathway enrichment for RIPK1,RIPK2,RIPK3,and RIPK6,and cell proliferation and DNA repair pathways for RIPK4 and RIPK5.RIPK family members showed heterogeneous alterations across cancers:for example,RIPK7 was mutated in up to~15%of u terine c orpus e ndometrial c arcinoma and l ung s quamous c ell c arcinoma cases,and RIPK1 and RIPK7 exhibited frequent promoter hypermethylation in multiple tumor types.Several genes displayed context-dependent associations with overall survival and with TMB/MSI.Conclusion:This pan-cancer analysis of the RIPK family reveals their diverse roles and potential as biomarkers and therapeutic targets.The findings emphasize the importance of RIPK genes in tumorigenesis and suggest context-dependent functions across cancer types.Further studies are needed to explore their mechanisms in cancer development and clinical applications.展开更多
It is significant to quantify the intermolecular physisorption extent in biomedical field.By taking the advantage of a significant difference from either sizes or weights,we introduced a combination of Scatchard equat...It is significant to quantify the intermolecular physisorption extent in biomedical field.By taking the advantage of a significant difference from either sizes or weights,we introduced a combination of Scatchard equation and either ultracentrifugation or size exclusion chromatography to obtain both the binding constant and the number of binding sites by using bovine serum albumin and eosin B as models.Compared to the photoluminescence quenching-based methods like Stern-Volmer and Hill equations,the introduced method is not only more precise but also simpler and more straightforward for the operation.Moreover,the protein conformational changes and the corresponding theoretical binding mode with an atomic resolution were also studied by using three-dimensional fluorescence spectroscopy and molecular docking method,respectively.These comparative results could help scientists select right methods to study any interactions between two molecules with significant differences from either sizes or weights.展开更多
Background: Triple-negative breast cancer (TNBC) is a highly heterogeneous breast cancersubtype characterized by the absence of expression of estrogen receptor (ER), progesteronereceptor (PR), and human epidermal grow...Background: Triple-negative breast cancer (TNBC) is a highly heterogeneous breast cancersubtype characterized by the absence of expression of estrogen receptor (ER), progesteronereceptor (PR), and human epidermal growth factor receptor 2 (HER2). TNBC exhibitsresistance to hormone and HER2-targeted therapy, along with a higher incidence ofrecurrence and poorer prognosis. Therefore, exploring the molecular features of TNBC andconstructing prognostic models are of significant importance for personalized treatmentstrategies. Methods: In this research, bioinformatics approaches were utilized to screendifferentially expressed genes in 405 TNBC cases and 128 normal tissue samples from 8 GEOdatasets. Key core genes and signaling pathways were further identified. Additionally, aprognostic model incorporating seven genes was established using clinical and pathologicalinformation from 169 TNBC cases in the TCGA dataset, and its predictive performance wasevaluated. Results: Functional analysis revealed dysregulated biological processes such asDNA replication, cell cycle, and mitotic chromosome separation in TNBC. Protein-proteininteraction network analysis identified ten core genes, including BUB1, BUB1B, CDK1,CDC20, CDCA8, CCNB1, CCNB2, KIF2C, NDC80, and CENPF. A prognostic model consistingof seven genes (EXO1, SHCBP1, ABRACL, DMD, THRB, DCDC2, and APOD) was establishedusing a step-wise Cox regression analysis. The model demonstrated good predictiveperformance in distinguishing patients' risk. Conclusion: This research provides importantinsights into the molecular characteristics of TNBC and establishes a reliable prognosticmodel for understanding its pathogenesis and predicting prognosis. These findingscontribute to the advancement of personalized treatment for TNBC.展开更多
Background:The ORAI1 gene,central to store-operated calcium entry(SOCE),is increasingly recognized for its pivotal role in cancer progression and patient prognosis across a broad spectrum of malignancies.Despite its c...Background:The ORAI1 gene,central to store-operated calcium entry(SOCE),is increasingly recognized for its pivotal role in cancer progression and patient prognosis across a broad spectrum of malignancies.Despite its critical involvement in calcium signaling pathways that are essential for cellular functions such as proliferation,migration,and apoptosis,the comprehensive impacts of ORAI1 within the tumor microenvironment(TME)and its modulation across various cancers have not been fully elucidated.Methods:We conducted a pan-cancer analysis leveraging data from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)to assess ORAI1 expression.Differential expression analyses were performed,complemented by correlative studies with tumor mutation burden(TMB),microsatellite instability(MSI),immune infiltration,and key biological processes and pathways.Results:Our results demonstrate that ORAI1 is consistently upregulated in a range of cancer types,associated with aggressive tumor characteristics and poor patient outcomes.Significantly,ORAI1 upregulation correlates with increased tumor mutation burden(TMB)and microsatellite instability(MSI),markers of genomic instability that are predictive of response to immunotherapy,underscoring its potential utility in clinical stratification and treatment decision-making.ORAI1's influence extended to the immune landscape,showing associations with immune cell infiltration and both immunosuppressive and immunostimulatory gene sets,thereby affecting the TME and possibly the efficacy of immunotherapeutic interventions.Conclusions:The multifaceted nature of ORAI1's involvement in cancer pathophysiology positions it as a prospective biomarker and therapeutic target.Its expression dynamics and correlative significance with prognostic and immune regulatory elements underscore its potential in guiding therapeutic strategies and improving clinical outcomes.This study lays a foundation for future research,aiming to leverage ORAI1's biological significance in cancer prognosis and therapy optimization.展开更多
Background:The nuclear receptor coactivator(NCOA)family,including NCOA1,NCOA2,and NCOA3,is critical in regulating gene expression through interactions with nuclear receptors and other transcription factors.These coact...Background:The nuclear receptor coactivator(NCOA)family,including NCOA1,NCOA2,and NCOA3,is critical in regulating gene expression through interactions with nuclear receptors and other transcription factors.These coactivators are implicated in various cancers,but their comprehensive roles across different cancer types remain poorly understood.Methods:We performed a pan-cancer bioinformatics analysis using data from The Cancer Genome Atlas and the Genotype-Tissue Expression project.We assessed the differential expression,copy number variations,mutations,methylation status,tumor mutation burden,microsatellite instability,and immune cell infiltration associated with NCOA family members across various cancers.Differential expression analysis was conducted using the DESeq2 package.Methylation data were analyzed using the ChAMP package,and immune cell infiltration was estimated using the CIBERSORT algorithm.Results:NCOA1 and NCOA2 were predominantly downregulated in multiple cancers,suggesting potential tumor suppressor roles,whereas NCOA3 was largely upregulated,indicating a consistent oncogenic function.These expression patterns significantly correlated with patient prognosis.Frequent copy number variations,particularly gains,and high mutation rates were observed in NCOA2.NCOA3 demonstrated consistent hypomethylation in tumors,which was associated with increased gene expression.Significant correlations were found between NCOA expression and tumor mutation burden,microsatellite instability,and immune cell infiltration,indicating their involvement in genomic instability and immune modulation.Conclusion:This comprehensive analysis reveals significant alterations in the expression,genomic,and epigenetic profiles of NCOA family members across various cancers.The findings highlight the multifaceted roles of NCOA1,NCOA2,and NCOA3 in tumorigenesis and their potential as biomarkers and therapeutic targets.Future research should focus on elucidating the mechanisms underlying the associations between NCOA expression,genomic alterations,and immune modulation to develop targeted cancer therapies.展开更多
Background:Doublecortin(DCX),a microtubule-associated protein,is best known for its critical role in neuronal migration during neural development,where it stabilizes microtubules and guides neurons to their proper pos...Background:Doublecortin(DCX),a microtubule-associated protein,is best known for its critical role in neuronal migration during neural development,where it stabilizes microtubules and guides neurons to their proper positions.Recently,DCX has been implicated in various cancer processes,suggesting it may influence tumor progression and the tumor microenvironment.Emerging evidence indicates that DCX can modulate cell migration,invasion,and interaction with immune cells,making it a potential player in oncogenesis.However,the role of DCX across different cancer types and its potential as a prognostic biomarker remain underexplored,necessitating a comprehensive analysis.Methods:We utilized The Cancer Genome Atlas to extract data on DCX expression in tumor and adjacent normal tissues across diverse cancer types.Differential expression analysis was conducted using differential expression sequencing 2.Survival analysis was performed with Kaplan-Meier estimates and Cox proportional hazards models.Correlations between DCX expression and tumor mutational burden,microsatellite instability,and immune infiltration were examined using Spearman’s correlation.Results:DCX showed variable expression across cancer types,with significant overexpression in certain tumors such as liver and lung cancer and downexpression in others like breast cancer.High DCX expression was correlated with poor prognosis in adrenocortical carcinoma but with better outcomes in low-grade glioma.Additionally,DCX expression was significantly associated with various immune markers and chemokines,suggesting a role in modulating the immune microenvironment.Conclusion:Our findings highlight the complex role of DCX in cancer,underlining its potential as a prognostic marker and its involvement in immune-related pathways.Targeting DCX could represent a novel approach to modulating tumor behavior and enhancing immune response in cancer therapy.展开更多
Neuroblastoma is the most prevalent solid tumor seen outside of the brain in children.Despite multimodal therapy,high-risk neuroblastoma has a 5-year survival rate of less than 50%.Necroptosis,an inflammatory form of ...Neuroblastoma is the most prevalent solid tumor seen outside of the brain in children.Despite multimodal therapy,high-risk neuroblastoma has a 5-year survival rate of less than 50%.Necroptosis,an inflammatory form of controlled cell death,has either anti-tumor or pro-tumor functions in several types of adult malignancies.However,the genes related to necroptosis and their association with prognosis in neuroblastoma are unclear.This study sought to determine the role of necroptosis-related genes in neuroblastoma a comprehensive bioinformatics analysis.Based on the expression of genes associated with necroptosis,the neuroblastoma samples were classified into three groups.We found that neuroblastoma with high necroptosis displayed promising outcomes and increased infiltration of immune cells.On the basis of the findings of the Cox regression analysis,we developed a four-gene prediction model consisting of PGAM family member 5(PGAM5),tumor necrosis factor(TNF),baculoviral IAP repeat containing 2(BIRC2),and fas associated via death domain(FADD)that is strongly linked with overall survival.The model exhibited superior performance,both internally and externally.Our data demonstrate that a high necroptosis rate correlates with favorable outcome and immune infiltration.These four necroptosis-related genes may serve as therapeutic targets,encouraging research on necroptosis in high-risk neuroblastoma therapy.展开更多
基金supported by grants from the Tianjin Health Technology Project(Grant no.2022QN106).
文摘Background:Receptor-interacting protein kinases(RIPKs)regulate cell death,inflammation,and immune responses,yet their roles in cancer are not fully understood.This study investigates the expression,genomic alterations,and functional implications of RIPK family members across various cancers.Methods:We collected multi-omics data from The Cancer Genome Atlas and other public databases,including gene expression,copy number variation(CNV),mutation,methylation,tumor mutation burden(TMB),and microsatellite instability(MSI).Differential expression and survival analyses were performed using DESeq2 and Cox proportional hazards models.CNV and mutation data were analyzed with GISTIC2 and Mutect2,and methylation data with the ChAMP package.Correlations with TMB and MSI were assessed using Pearson coefficients,and gene set enrichment analysis was conducted with the MSigDB Hallmark gene sets.Results:RIPK family members show significant differential expression in various cancers,with RIPK1 and RIPK4 frequently altered.Survival analysis reveals heterogeneous impacts on overall survival.CNV and mutation analyses identify high alteration frequencies for RIPK2 and RIPK7,affecting gene expression.RIPK1 and RIPK7 are hypermethylated in several cancers,inversely correlating with RIPK3 expression.RIPK1,RIPK2,RIPK5,RIPK6,and RIPK7 correlate positively with TMB,while RIPK3 shows negative correlations in some cancers.MSI analysis indicates associations with DNA mismatch repair.G ene set enrichment analysis highlights immune-related pathway enrichment for RIPK1,RIPK2,RIPK3,and RIPK6,and cell proliferation and DNA repair pathways for RIPK4 and RIPK5.RIPK family members showed heterogeneous alterations across cancers:for example,RIPK7 was mutated in up to~15%of u terine c orpus e ndometrial c arcinoma and l ung s quamous c ell c arcinoma cases,and RIPK1 and RIPK7 exhibited frequent promoter hypermethylation in multiple tumor types.Several genes displayed context-dependent associations with overall survival and with TMB/MSI.Conclusion:This pan-cancer analysis of the RIPK family reveals their diverse roles and potential as biomarkers and therapeutic targets.The findings emphasize the importance of RIPK genes in tumorigenesis and suggest context-dependent functions across cancer types.Further studies are needed to explore their mechanisms in cancer development and clinical applications.
基金supported by the National Natural Science Foundation of China(Nos.21171086 and 81160213)the Inner Mongolia Autonomous Region science and Technology Department(No.211-202077)+2 种基金the Inner Mongolia Grassland Talent(No.108-108038)the Natural Science Foundation of Inner Mongolia Autonomous Region of China(Nos.2013MS1121,2015ms0806 and 2016MS0211)the Inner Mongolia Agricultural University(Nos.109-108040,211-109003 and 211-206038)
文摘It is significant to quantify the intermolecular physisorption extent in biomedical field.By taking the advantage of a significant difference from either sizes or weights,we introduced a combination of Scatchard equation and either ultracentrifugation or size exclusion chromatography to obtain both the binding constant and the number of binding sites by using bovine serum albumin and eosin B as models.Compared to the photoluminescence quenching-based methods like Stern-Volmer and Hill equations,the introduced method is not only more precise but also simpler and more straightforward for the operation.Moreover,the protein conformational changes and the corresponding theoretical binding mode with an atomic resolution were also studied by using three-dimensional fluorescence spectroscopy and molecular docking method,respectively.These comparative results could help scientists select right methods to study any interactions between two molecules with significant differences from either sizes or weights.
文摘Background: Triple-negative breast cancer (TNBC) is a highly heterogeneous breast cancersubtype characterized by the absence of expression of estrogen receptor (ER), progesteronereceptor (PR), and human epidermal growth factor receptor 2 (HER2). TNBC exhibitsresistance to hormone and HER2-targeted therapy, along with a higher incidence ofrecurrence and poorer prognosis. Therefore, exploring the molecular features of TNBC andconstructing prognostic models are of significant importance for personalized treatmentstrategies. Methods: In this research, bioinformatics approaches were utilized to screendifferentially expressed genes in 405 TNBC cases and 128 normal tissue samples from 8 GEOdatasets. Key core genes and signaling pathways were further identified. Additionally, aprognostic model incorporating seven genes was established using clinical and pathologicalinformation from 169 TNBC cases in the TCGA dataset, and its predictive performance wasevaluated. Results: Functional analysis revealed dysregulated biological processes such asDNA replication, cell cycle, and mitotic chromosome separation in TNBC. Protein-proteininteraction network analysis identified ten core genes, including BUB1, BUB1B, CDK1,CDC20, CDCA8, CCNB1, CCNB2, KIF2C, NDC80, and CENPF. A prognostic model consistingof seven genes (EXO1, SHCBP1, ABRACL, DMD, THRB, DCDC2, and APOD) was establishedusing a step-wise Cox regression analysis. The model demonstrated good predictiveperformance in distinguishing patients' risk. Conclusion: This research provides importantinsights into the molecular characteristics of TNBC and establishes a reliable prognosticmodel for understanding its pathogenesis and predicting prognosis. These findingscontribute to the advancement of personalized treatment for TNBC.
基金grants from the Tianjin Health Technology Project(Grant no.2022QN106).
文摘Background:The ORAI1 gene,central to store-operated calcium entry(SOCE),is increasingly recognized for its pivotal role in cancer progression and patient prognosis across a broad spectrum of malignancies.Despite its critical involvement in calcium signaling pathways that are essential for cellular functions such as proliferation,migration,and apoptosis,the comprehensive impacts of ORAI1 within the tumor microenvironment(TME)and its modulation across various cancers have not been fully elucidated.Methods:We conducted a pan-cancer analysis leveraging data from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)to assess ORAI1 expression.Differential expression analyses were performed,complemented by correlative studies with tumor mutation burden(TMB),microsatellite instability(MSI),immune infiltration,and key biological processes and pathways.Results:Our results demonstrate that ORAI1 is consistently upregulated in a range of cancer types,associated with aggressive tumor characteristics and poor patient outcomes.Significantly,ORAI1 upregulation correlates with increased tumor mutation burden(TMB)and microsatellite instability(MSI),markers of genomic instability that are predictive of response to immunotherapy,underscoring its potential utility in clinical stratification and treatment decision-making.ORAI1's influence extended to the immune landscape,showing associations with immune cell infiltration and both immunosuppressive and immunostimulatory gene sets,thereby affecting the TME and possibly the efficacy of immunotherapeutic interventions.Conclusions:The multifaceted nature of ORAI1's involvement in cancer pathophysiology positions it as a prospective biomarker and therapeutic target.Its expression dynamics and correlative significance with prognostic and immune regulatory elements underscore its potential in guiding therapeutic strategies and improving clinical outcomes.This study lays a foundation for future research,aiming to leverage ORAI1's biological significance in cancer prognosis and therapy optimization.
基金supported by grants from the Tianjin Health Technology Project(Grant No.2022QN106).
文摘Background:The nuclear receptor coactivator(NCOA)family,including NCOA1,NCOA2,and NCOA3,is critical in regulating gene expression through interactions with nuclear receptors and other transcription factors.These coactivators are implicated in various cancers,but their comprehensive roles across different cancer types remain poorly understood.Methods:We performed a pan-cancer bioinformatics analysis using data from The Cancer Genome Atlas and the Genotype-Tissue Expression project.We assessed the differential expression,copy number variations,mutations,methylation status,tumor mutation burden,microsatellite instability,and immune cell infiltration associated with NCOA family members across various cancers.Differential expression analysis was conducted using the DESeq2 package.Methylation data were analyzed using the ChAMP package,and immune cell infiltration was estimated using the CIBERSORT algorithm.Results:NCOA1 and NCOA2 were predominantly downregulated in multiple cancers,suggesting potential tumor suppressor roles,whereas NCOA3 was largely upregulated,indicating a consistent oncogenic function.These expression patterns significantly correlated with patient prognosis.Frequent copy number variations,particularly gains,and high mutation rates were observed in NCOA2.NCOA3 demonstrated consistent hypomethylation in tumors,which was associated with increased gene expression.Significant correlations were found between NCOA expression and tumor mutation burden,microsatellite instability,and immune cell infiltration,indicating their involvement in genomic instability and immune modulation.Conclusion:This comprehensive analysis reveals significant alterations in the expression,genomic,and epigenetic profiles of NCOA family members across various cancers.The findings highlight the multifaceted roles of NCOA1,NCOA2,and NCOA3 in tumorigenesis and their potential as biomarkers and therapeutic targets.Future research should focus on elucidating the mechanisms underlying the associations between NCOA expression,genomic alterations,and immune modulation to develop targeted cancer therapies.
基金Tianjin Health Technology Project(Grant no.2022QN106).
文摘Background:Doublecortin(DCX),a microtubule-associated protein,is best known for its critical role in neuronal migration during neural development,where it stabilizes microtubules and guides neurons to their proper positions.Recently,DCX has been implicated in various cancer processes,suggesting it may influence tumor progression and the tumor microenvironment.Emerging evidence indicates that DCX can modulate cell migration,invasion,and interaction with immune cells,making it a potential player in oncogenesis.However,the role of DCX across different cancer types and its potential as a prognostic biomarker remain underexplored,necessitating a comprehensive analysis.Methods:We utilized The Cancer Genome Atlas to extract data on DCX expression in tumor and adjacent normal tissues across diverse cancer types.Differential expression analysis was conducted using differential expression sequencing 2.Survival analysis was performed with Kaplan-Meier estimates and Cox proportional hazards models.Correlations between DCX expression and tumor mutational burden,microsatellite instability,and immune infiltration were examined using Spearman’s correlation.Results:DCX showed variable expression across cancer types,with significant overexpression in certain tumors such as liver and lung cancer and downexpression in others like breast cancer.High DCX expression was correlated with poor prognosis in adrenocortical carcinoma but with better outcomes in low-grade glioma.Additionally,DCX expression was significantly associated with various immune markers and chemokines,suggesting a role in modulating the immune microenvironment.Conclusion:Our findings highlight the complex role of DCX in cancer,underlining its potential as a prognostic marker and its involvement in immune-related pathways.Targeting DCX could represent a novel approach to modulating tumor behavior and enhancing immune response in cancer therapy.
文摘Neuroblastoma is the most prevalent solid tumor seen outside of the brain in children.Despite multimodal therapy,high-risk neuroblastoma has a 5-year survival rate of less than 50%.Necroptosis,an inflammatory form of controlled cell death,has either anti-tumor or pro-tumor functions in several types of adult malignancies.However,the genes related to necroptosis and their association with prognosis in neuroblastoma are unclear.This study sought to determine the role of necroptosis-related genes in neuroblastoma a comprehensive bioinformatics analysis.Based on the expression of genes associated with necroptosis,the neuroblastoma samples were classified into three groups.We found that neuroblastoma with high necroptosis displayed promising outcomes and increased infiltration of immune cells.On the basis of the findings of the Cox regression analysis,we developed a four-gene prediction model consisting of PGAM family member 5(PGAM5),tumor necrosis factor(TNF),baculoviral IAP repeat containing 2(BIRC2),and fas associated via death domain(FADD)that is strongly linked with overall survival.The model exhibited superior performance,both internally and externally.Our data demonstrate that a high necroptosis rate correlates with favorable outcome and immune infiltration.These four necroptosis-related genes may serve as therapeutic targets,encouraging research on necroptosis in high-risk neuroblastoma therapy.
