RESUMO
Background: African ancestry is a known factor associated with the presentation and aggressiveness of prostate cancer (PC). Hispanic/Latino populations exhibit varying degrees of genetic admixture across Latin American countries, leading to diverse levels of African ancestry. However, it remains unclear whether genetic ancestry plays a role in the aggressiveness of PC in Hispanic/Latino patients. We explored the associations between genetic ancestry and the clinicopathological data in Hispanic/Latino PC patients from Colombia. Patients and methods: We estimated the European, Indigenous and African genetic ancestry, of 230 Colombian patients with localized/regionally advanced PC through a validated panel for genotypification of 106 Ancestry Informative Markers. We examined the associations of the genetic ancestry components with the Gleason Grade Groups (GG) and the clinicopathological characteristics. Results: No association was observed between the genetic ancestry with the biochemical recurrence or Gleason GG; however, in a two groups comparison, there were statistically significant differences between GG3 and GG4/GG5 for European ancestry, with a higher mean ancestry proportion in GG4/GG5. A lower risk of being diagnosed at an advanced age was observed for patients with high African ancestry than those with low African ancestry patients (OR: 0.96, CI: 0.92-0.99, p=0.03). Conclusion: Our findings revealed an increased risk of presentation of PC at an earlier age in patients with higher African ancestry compared to patients with lower African ancestry in our Hispanic/Latino patients.
RESUMO
BACKGROUND: The role of ERG-status molecular subtyping in prognosis of prostate cancer (PCa) is still under debate. In this study, we identified differentially expressed genes (DEGs) according to ERG-status to explore their enriched pathways and implications in prognosis in Hispanic/Latino PCa patients. METHODS: RNA from 78 Hispanic PCa tissues from radical prostatectomies (RP) were used for RNA-sequencing. ERGhigh /ERGlow tumor groups were determined based on the 1.5-fold change median expression in non-tumor samples. DEGs with a False Discovery Rate (FDR) < 0.01 and a fold change >2 were identified between ERGhigh and ERGlow tumors and submitted to enrichment analysis in MetaCore. Survival and association analyses were performed to evaluate biochemical recurrence (BCR)-free survival. RESULTS: The identification of 150 DEGs between ERGhigh and ERGlow tumors revealed clustering of most of the non-BCR cases (60%) into de ERGhigh group and most of the BCR cases (60.8%) in ERGlow group. Kaplan-Meier survival curves showed a worst BCR-free survival for ERGlow patients, and a significant reduced risk of BCR was observed for ERGhigh cases (OR = 0.29 (95%CI, 0.10-0.8)). Enrichment pathway analysis identified metabolic-related pathways, such as the renin-angiotensin system and angiotensin maturation system, the linoleic acid metabolism, and polyamines metabolism in these ERG groups. CONCLUSIONS: ERGlow tumor cases were associated with poor BCR-free survival in our Hispanic/Latino patients, with metabolism-related pathways altered in the BCR progression. IMPACT: Our findings suggest the need to dissect the role of diet, metabolism, and lifestyle as risk factors for more aggressive PCa subtypes.
