Abstract 3514: DNA methylation markers for risk of metastasis in a cohort of men with localized prostate cancer

作者：Kim Cannavale, Jeff Slezak, Yu‐Hsiang Shu, Gary W. Chien, Xu-Feng Chen, Feng Shi, Kim Siegmund, Stephen Van Den Eeden, Jiaoti Huang, Chun Chao · 发表于：Cancer Research · 年份：2020 · DOI：10.1158/1538-7445.am2020-3514 · 研究领域：Prostate Cancer Treatment and Research、Cancer-related molecular mechanisms research、Prostate Cancer Diagnosis and Treatment

Abstract Background: Most localized prostate cancers (PCa) are indolent and will not require treatment, but a small proportion can progress to metastasis. Distinguishing aggressive from indolent tumors can better inform treatment decisions. There has been interest in cancer genomics to predict PCa aggressiveness but with no consensus on methylation's role. We examined whether DNA methylation status of selected candidate genes can predict risk of PCa metastasis in the absence of curative treatment. Methods: A retrospective cohort of men diagnosed with PCa at Kaiser Permanente Southern California 1997-2007 who met the following inclusion criteria were identified: (1) diagnosed at stage I and II and (2) did not receive PCa treatment for at least 6 months after diagnosis. Men were followed for metastasis and censored at the initiation of prostatectomy or radiation, non-PCa related death, membership termination, or end of 2016. Potential metastasis was identified by an algorithm, then manually reviewed and confirmed. For each metastasis case, up to 4 controls were selected using density sampling, matched on age, race (black vs. non-black) and Gleason grade. For each case and control, FFPE blocks of diagnostic prostate biopsy cores were retrieved. The study pathologists reviewed the H/E slides and circled cancerous areas, which were macro-dissected for DNA extraction. Methylation status was obtained using Illumina's Infinium Methylation EPIC BeadChip. The candidate genes (N=118) we...