目前的诊断工具无法区分低级别惰性前列腺癌 (PrCa) 和具有转移性和/或致命倾向的前列腺癌。最近的证据表明，转录组的重编程可能驱动转移表型，并且这种重编程至少部分地受到癌细胞 DNA 的表观遗传变化（包括甲基化）的控制。这些变化被称为“表观遗传驱动因素”，之前已与癌细胞存活相关。在这里，使用配对的原发性 PrCa 和转移性骨样本的 Illumina 甲基化 EPIC 阵列数据，我们将 WNT5A 确定为 PrCa 转移的推定表观驱动因素。与转移性骨样品和 PC-3 细胞相比，在原发性 PrCa 样品和 22Rv1 细胞中观察到显着更高的 WNT5A 甲基化。这种较高的甲基化与显着较低的 WNT5A 基因表达相关。鉴于转移性癌症患者（尤其是那些疾病已转移至骨骼的患者）可用的有效疗法有限，WNT5A 是潜在的治疗靶标。© 2024 作者。约翰·威利出版的癌症医学

Current diagnostic tools are unable to distinguish low-grade indolent prostate cancer (PrCa) from that with a propensity to become metastatic and/or lethal. Recent evidence suggests that reprogramming of the transcriptome may drive the metastatic phenotype, and that this reprogramming is controlled, at least in part, by epigenetic changes to the DNA of cancer cells, including methylation. These changes, referred to as 'epigenetic drivers,' have previously been associated with cancer cell survival.Here, using Illumina Methylation EPIC array data of paired primary PrCa and metastatic bone samples, we identified WNT5A as a putative epi-driver of PrCa metastasis to the bone, which was further validated in vitro.Significantly higher WNT5A methylation was observed in primary PrCa samples and 22Rv1 cells compared to metastatic bone samples and PC-3 cells. This higher methylation was associated with significantly lower WNT5A gene expression.Given the limited effective therapies available for metastatic cancer sufferers, particularly those whose disease has metastasised to the bone, WNT5A presents as a potential putative target for therapy.© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.