The present study analyzed the predictive value of combined analysis of collapsin response mediator protein 4 （CRMP4） methylation levels and the Cancer of the Prostate Risk Assessment （CAPRA-S） Postsurgical score ...The present study analyzed the predictive value of combined analysis of collapsin response mediator protein 4 （CRMP4） methylation levels and the Cancer of the Prostate Risk Assessment （CAPRA-S） Postsurgical score of patients who required adjuvant hormone therapy （AHT） after radical prostatectomy （RP）, We retrospectively analyzed 305 patients with prostate cancer （PCa） who received RP and subsequent androgen deprivation therapy （ADT）. Two hundred and thirty patients with clinically high-risk PCa underwent immediate ADT, and 75 patients with intermediate risk PCa underwent deferred ADT. CRMP4 methylation levels in biopsies were determined, and CAPRA-S scores were calculated. In the deferred ADT group, the values of the hazard ratios for tumor progression and cancer-specific mortality （CSM） in patients with 〉15% CRMP4 methylation were 6.81 （95% CI, 2.34-19.80） and 12.83 （95% CI. 2.16-26.10）, respectively. Receiver-operating characteristic curve analysis indicated that CRMP4 methylation levels 〉15% served as a significant prognostic marker of tumor progression and CSM. In the immediate ADT group, CAPRA-S scores ：〉6 and CRMP4 methylation levels ：〉15% were independent predictors of these outcomes （uni- and multi-variable Cox regression analyses）. The differences in the 5-year progression-free survival between each combination were statistically significant. Combining CAPRA-S score and CRMP4 methylation levels improved the area under the curve compared with the CRMP4 or CAPRA-S model. Therefore, CRMP4 methylation levels ：〉15% were significantly associated with a poor prognosis and their combination with CAPRA-S score accurately predicted tumor progression and metastasis for patients requiring AHT after RP.展开更多
Background:Epigenetic regulation of the gene expression results from interaction between the external environment and transcription of the genetic information encoded in DNA.Methylated CpG regions within the gene prom...Background:Epigenetic regulation of the gene expression results from interaction between the external environment and transcription of the genetic information encoded in DNA.Methylated CpG regions within the gene promoters lead to silencing of the gene expression in most cases.Factors contributing to epigenetic regulation include intestinal microbiota,which in chicken can be potently modified by in ovo stimulation.The main aim of this study was to determine global and specific methylation patterns of the spleen under the influence of host-microbiome interaction.Results:Fertilized eggs of two genotypes:Ross 308 and Green-legged Partridgelike were in ovo stimulated on d 12 of incubation.The injected compounds were as follows:probiotic-Lactococcus lactis subsp.cremoris IBB477,prebiotic-galactooligosaccharides,and synbiotic-combination of both.Chickens were sacrificed on d 42 post-hatching.Spleen was collected,RNA and DNA were isolated and intended to gene expression,gene methylation and global methylation analysis.We have proved that negative regulation of gene expression after administration of bioactive substances in ovo might have epigenetic character.Epigenetic changes depend on the genotype and the substance administered in ovo.Conclusion:Epigenetic nature of microbial reprogramming in poultry and extension of issues related to hostmicrobiome interaction is a new direction of this research.展开更多
Background Chickens and ducks are vital sources of animal protein for humans.Recent pangenome studies suggest that a single genome is insufficient to represent the genetic information of a species,highlighting the nee...Background Chickens and ducks are vital sources of animal protein for humans.Recent pangenome studies suggest that a single genome is insufficient to represent the genetic information of a species,highlighting the need for more comprehensive genomes.The bird genome has more than tens of microchromosomes,but comparative genomics,annotations,and the discovery of variations are hindered by inadequate telomere-to-telomere level assemblies.We aim to complete the chicken and duck genomes,recover missing genes,and reveal common and unique chromosomal features between birds.Results The near telomere-to-telomere genomes of Silkie Gallus gallus and Mallard Anas platyrhynchos were successfully assembled via multiple high-coverage complementary technologies,with quality values of 36.65 and 44.17 for Silkie and Mallard,respectively;and BUSCO scores of 96.55%and 96.97%for Silkie and Mallard,respectively;the mapping rates reached over 99.52%for both assembled genomes,these evaluation results ensured high completeness and accuracy.We successfully annotated 20,253 and 19,621 protein-coding genes for Silkie and Mallard,respectively,and assembled gap-free sex chromosomes in Mallard for the first time.Comparative analysis revealed that microchromosomes differ from macrochromosomes in terms of GC content,repetitive sequence abundance,gene density,and levels of 5mC methylation.Different types of arrangements of centromeric repeat sequence centromeres exist in both Silkie and the Mallard genomes,with Mallard centromeres being invaded by CR1.The highly heterochromatic W chromosome,which serves as a refuge for ERVs,contains disproportionately long ERVs.Both Silkie and the Mallard genomes presented relatively high 5mC methylation levels on sex chromosomes and microchromosomes,and the telomeres and centromeres presented significantly higher 5mC methylation levels than the whole genome.Finally,we recovered 325 missing genes via our new genomes and annotated TNFA in Mallard for the first time,revealing conserved protein structures and tissue-specific expression.Conclusions The near telomere-to-telomere assemblies in Mallard and Silkie,with the first gap-free sex chromosomes in ducks,significantly enhanced our understanding of genetic structures in birds,specifically highlighting the distinctive chromosome features between the chicken and duck genomes.This foundational work also provides a series of newly identified missing genes for further investigation.展开更多
文摘The present study analyzed the predictive value of combined analysis of collapsin response mediator protein 4 （CRMP4） methylation levels and the Cancer of the Prostate Risk Assessment （CAPRA-S） Postsurgical score of patients who required adjuvant hormone therapy （AHT） after radical prostatectomy （RP）, We retrospectively analyzed 305 patients with prostate cancer （PCa） who received RP and subsequent androgen deprivation therapy （ADT）. Two hundred and thirty patients with clinically high-risk PCa underwent immediate ADT, and 75 patients with intermediate risk PCa underwent deferred ADT. CRMP4 methylation levels in biopsies were determined, and CAPRA-S scores were calculated. In the deferred ADT group, the values of the hazard ratios for tumor progression and cancer-specific mortality （CSM） in patients with 〉15% CRMP4 methylation were 6.81 （95% CI, 2.34-19.80） and 12.83 （95% CI. 2.16-26.10）, respectively. Receiver-operating characteristic curve analysis indicated that CRMP4 methylation levels 〉15% served as a significant prognostic marker of tumor progression and CSM. In the immediate ADT group, CAPRA-S scores ：〉6 and CRMP4 methylation levels ：〉15% were independent predictors of these outcomes （uni- and multi-variable Cox regression analyses）. The differences in the 5-year progression-free survival between each combination were statistically significant. Combining CAPRA-S score and CRMP4 methylation levels improved the area under the curve compared with the CRMP4 or CAPRA-S model. Therefore, CRMP4 methylation levels ：〉15% were significantly associated with a poor prognosis and their combination with CAPRA-S score accurately predicted tumor progression and metastasis for patients requiring AHT after RP.
基金supported by grant UMO-2017/25/N/NZ9/01822 funded by the National Science Centre in Cracow(Poland).
文摘Background:Epigenetic regulation of the gene expression results from interaction between the external environment and transcription of the genetic information encoded in DNA.Methylated CpG regions within the gene promoters lead to silencing of the gene expression in most cases.Factors contributing to epigenetic regulation include intestinal microbiota,which in chicken can be potently modified by in ovo stimulation.The main aim of this study was to determine global and specific methylation patterns of the spleen under the influence of host-microbiome interaction.Results:Fertilized eggs of two genotypes:Ross 308 and Green-legged Partridgelike were in ovo stimulated on d 12 of incubation.The injected compounds were as follows:probiotic-Lactococcus lactis subsp.cremoris IBB477,prebiotic-galactooligosaccharides,and synbiotic-combination of both.Chickens were sacrificed on d 42 post-hatching.Spleen was collected,RNA and DNA were isolated and intended to gene expression,gene methylation and global methylation analysis.We have proved that negative regulation of gene expression after administration of bioactive substances in ovo might have epigenetic character.Epigenetic changes depend on the genotype and the substance administered in ovo.Conclusion:Epigenetic nature of microbial reprogramming in poultry and extension of issues related to hostmicrobiome interaction is a new direction of this research.
基金supported by the National Key R&D Program of China(2022YFF1000100,2023YFD1300300)the National Natural Science Foundation of China(31572388,31972525)the China Agriculture Research System of MOF and MARA(CARS-41)。
文摘Background Chickens and ducks are vital sources of animal protein for humans.Recent pangenome studies suggest that a single genome is insufficient to represent the genetic information of a species,highlighting the need for more comprehensive genomes.The bird genome has more than tens of microchromosomes,but comparative genomics,annotations,and the discovery of variations are hindered by inadequate telomere-to-telomere level assemblies.We aim to complete the chicken and duck genomes,recover missing genes,and reveal common and unique chromosomal features between birds.Results The near telomere-to-telomere genomes of Silkie Gallus gallus and Mallard Anas platyrhynchos were successfully assembled via multiple high-coverage complementary technologies,with quality values of 36.65 and 44.17 for Silkie and Mallard,respectively;and BUSCO scores of 96.55%and 96.97%for Silkie and Mallard,respectively;the mapping rates reached over 99.52%for both assembled genomes,these evaluation results ensured high completeness and accuracy.We successfully annotated 20,253 and 19,621 protein-coding genes for Silkie and Mallard,respectively,and assembled gap-free sex chromosomes in Mallard for the first time.Comparative analysis revealed that microchromosomes differ from macrochromosomes in terms of GC content,repetitive sequence abundance,gene density,and levels of 5mC methylation.Different types of arrangements of centromeric repeat sequence centromeres exist in both Silkie and the Mallard genomes,with Mallard centromeres being invaded by CR1.The highly heterochromatic W chromosome,which serves as a refuge for ERVs,contains disproportionately long ERVs.Both Silkie and the Mallard genomes presented relatively high 5mC methylation levels on sex chromosomes and microchromosomes,and the telomeres and centromeres presented significantly higher 5mC methylation levels than the whole genome.Finally,we recovered 325 missing genes via our new genomes and annotated TNFA in Mallard for the first time,revealing conserved protein structures and tissue-specific expression.Conclusions The near telomere-to-telomere assemblies in Mallard and Silkie,with the first gap-free sex chromosomes in ducks,significantly enhanced our understanding of genetic structures in birds,specifically highlighting the distinctive chromosome features between the chicken and duck genomes.This foundational work also provides a series of newly identified missing genes for further investigation.
