Differential DNA Methylation in Prostate Tumors from Puerto Rican Men.

Gilberto Ruiz-Deya,Julie Dutil,Youngchul Kim,Anders Berglund,Jong Y Park,Ryan Putney,Jarline Encarnación-Medina,Carmen Ortiz-Sanchéz,Jasreman Dhillon,Jaime Matta

doi:10.3390/ijms22020733

Abstract

In 2020, approximately 191,930 new prostate cancer (PCa) cases are estimated in the United States (US). Hispanic/Latinos (H/L) are the second largest racial/ethnic group in the US. This study aims to assess methylation patterns between aggressive and indolent PCa including DNA repair genes along with ancestry proportions. Prostate tumors classified as aggressive (n = 11) and indolent (n = 13) on the basis of the Gleason score were collected. Tumor and adjacent normal tissue were annotated on H&E (Haemotoxylin and Eosin) slides and extracted by macro-dissection. Methylation patterns were assessed using the Illumina 850K DNA methylation platform. Raw data were processed using the Bioconductor package. Global ancestry proportions were estimated using ADMIXTURE (k = 3). One hundred eight genes including AOX1 were differentially methylated in tumor samples. Regarding the PCa aggressiveness, six hypermethylated genes (RREB1, FAM71F2, JMJD1C, COL5A3, RAE1, and GABRQ) and 11 hypomethylated genes (COL9A2, FAM179A, SLC17A2, PDE10A, PLEKHS1, TNNI2, OR51A4, RNF169, SPNS2, ADAMTSL5, and CYP4F12) were identified. Two significant differentially methylated DNA repair genes, JMJD1C and RNF169, were found. Ancestry proportion results for African, European, and Indigenous American were 24.1%, 64.2%, and 11.7%, respectively. The identification of DNA methylation patterns related to PCa in H/L men along with specific patterns related to aggressiveness and DNA repair constitutes a pivotal effort for the understanding of PCa in this population.

Highlights

Since 1984, prostate cancer (PCa) has been the most commonly diagnosed cancer in the United States (US), currently accounting for 19% of all cancers in men
Chinea et al (2017) reported that H/L subgroups have different prostate cancerspecific mortality (PCSM) rates when compared to non-Hispanic Whites (NHWs) and non-Hispanic Blacks (NHBs) using data from 2000–2013 that included 486,865 men
No differences between the two groups were evident in terms of prostate-specific antigen (PSA) levels, ethnicity, vital characteristics, biochemical recurrence, tumor stage, surgical margins, and family history of prostate cancer (p > 0.05)

Summary

Introduction

Since 1984, prostate cancer (PCa) has been the most commonly diagnosed cancer in the United States (US), currently accounting for 19% of all cancers in men. 12.1% of men will be diagnosed with PCa in their lifetime [1]. 191,930 new PCa cases and 33,330 deaths are estimated in the US [2]. Hispanic/Latinos (H/L) are the second largest racial/ethnic group in the US after non-Hispanic Whites (NHWs). Chinea et al (2017) reported that H/L subgroups have different prostate cancerspecific mortality (PCSM) rates when compared to NHWs and non-Hispanic Blacks (NHBs) using data from 2000–2013 that included 486,865 men.

Methods

Results

Conclusion