Autor: |
Ruiz-Deya G; Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University-School of Medicine, Ponce 00716-2347, Puerto Rico., Matta J; Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University-School of Medicine, Ponce 00716-2347, Puerto Rico., Encarnación-Medina J; Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University-School of Medicine, Ponce 00716-2347, Puerto Rico., Ortiz-Sanchéz C; Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University-School of Medicine, Ponce 00716-2347, Puerto Rico., Dutil J; Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University-School of Medicine, Ponce 00716-2347, Puerto Rico., Putney R; Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA., Berglund A; Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA., Dhillon J; Department of Pathology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA., Kim Y; Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA., Park JY; Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA. |
Abstrakt: |
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. |