Pedersen Christine Aaserød, Fleischer Thomas, Wess Maximilian, Midtbust Elise, Andersen Maria K, Viset Trond, Størkersen Øystein, Rye Morten B, Tessem May-Britt
Department of Circulation and Medical Imaging, NTNU, Trondheim, Norway.
Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
Clin Epigenetics. 2025 Jul 21;17(1):127. doi: 10.1186/s13148-025-01932-x.
There is a need for more precise biomarkers and understanding on the development of aggressive prostate cancer. In this study, we analyzed DNA methylation in 64 prostate cancer tissue samples, using tissue from radical prostatectomy patients (n = 16) with up to 16 years of clinical follow-up. We used several samples from each patient including both normal and cancer tissue to study DNA methylation patterns in relation to aggressiveness measured by follow-up data of biochemical recurrence and metastasis status as clinical endpoints. We identified differentially methylated CpGs associated with recurrence and metastasis, regardless of whether the tissue was normal, cancer-adjacent normal, or cancer. The identified CpG sites were over-represented in promoter regions and transcription factor binding regions, suggesting their influence on gene expression regulation. They further exhibited low intrapatient heterogeneity both between normal, normal adjacent, and cancer tissue, making them favorable as potential biomarkers for aggressive prostate cancer. However, validation of a subset of these CpGs in an external dataset was unsuccessful.
对于侵袭性前列腺癌的发展，需要更精确的生物标志物以及更深入的了解。在本研究中，我们分析了64例前列腺癌组织样本中的DNA甲基化情况，这些样本取自接受根治性前列腺切除术的患者（n = 16），并进行了长达16年的临床随访。我们从每位患者获取了多个样本，包括正常组织和癌组织，以研究与侵袭性相关的DNA甲基化模式，侵袭性通过生化复发和转移状态的随访数据作为临床终点来衡量。我们鉴定出了与复发和转移相关的差异甲基化CpG，无论组织是正常的、癌旁正常的还是癌组织。所鉴定出的CpG位点在启动子区域和转录因子结合区域中过度富集，表明它们对基因表达调控有影响。它们在正常组织、正常相邻组织和癌组织之间还表现出较低的患者内异质性，使其有望成为侵袭性前列腺癌的潜在生物标志物。然而，在外部数据集中对这些CpG的一个子集进行验证未成功。
