Combined analysis of CRMP4 methylation levels and CAPRA-S score predicts metastasis and outcomes in prostate cancer patients

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.

Interaction between early in ovo stimulation of the gut microbiota and chicken host-splenic changes in gene expression and methylation

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.