학술논문

Genome‐wide methylation profiling of diagnostic tumor specimens identified DNA methylation markers associated with metastasis among men with untreated localized prostate cancer
Document Type
article
Source
Cancer Medicine, Vol 12, Iss 18, Pp 18837-18849 (2023)
Subject
epigenetics
metastasis
methylation
prostate cancer
risk model
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Language
English
ISSN
2045-7634
Abstract
Abstract Background We used a genome‐wide discovery approach to identify methylation markers associated with metastasis in men with localized prostate cancer (PCa), as better identification of those at high risk of metastasis can inform treatment decision‐making. Methods We identified men with localized PCa at Kaiser Permanente California (January 1, 1997–December 31, 2006) who did not receive curative treatment and followed them for 10 years to determine metastasis status. Cases were chart review‐confirmed metastasis, and controls were matched using density sampling. We extracted DNA from the cancerous areas in the archived diagnostic tissue blocks. We used Illumina's Infinium MethylationEPIC BeadChip for methylation interrogation. We used conditional logistic regression and Bonferroni's correction to identify methylation markers associated with metastasis. In a separate validation cohort (2007), we evaluated the added predictive utility of the methylation score beyond clinical risk score. Results Among 215 cases and 404 controls, 31 CpG sites were significantly associated with metastasis status. Adding the methylation score to the clinical risk score did not meaningfully improve the c‐statistic (0.80–0.81) in the validation cohort, though the score itself was statistically significant (p