We read with the great interest the study by Ababneh et al in which inducedmesenchymal stem cell-derived exosomes were shown to exhibit a stronger andmore sustained anti-proliferative effect by inducing a senescence-l...We read with the great interest the study by Ababneh et al in which inducedmesenchymal stem cell-derived exosomes were shown to exhibit a stronger andmore sustained anti-proliferative effect by inducing a senescence-like state withoutapoptosis.The results obtained by the authors highlight the features of theeffects of senescent drift induction in surrounding tissues.In the light of thesefindings,the role of the properties of extracellular matrix and cellular glycocalyxin responses of human tumors to therapy remain uninvestigated.These extracellularbarriers appear to be significant obstacles to effective cancer therapy,especiallyin relation to the use of unique properties of tumor microenvironment forthe immunotherapy-resistant cancer treatment.展开更多
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
文摘We read with the great interest the study by Ababneh et al in which inducedmesenchymal stem cell-derived exosomes were shown to exhibit a stronger andmore sustained anti-proliferative effect by inducing a senescence-like state withoutapoptosis.The results obtained by the authors highlight the features of theeffects of senescent drift induction in surrounding tissues.In the light of thesefindings,the role of the properties of extracellular matrix and cellular glycocalyxin responses of human tumors to therapy remain uninvestigated.These extracellularbarriers appear to be significant obstacles to effective cancer therapy,especiallyin relation to the use of unique properties of tumor microenvironment forthe immunotherapy-resistant cancer treatment.
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.
