Ito Tomoaki, Iwasawa Takumi, Sakuraba Shunsuke, Tanaka Kenichiro
Department of Surgery, Juntendo University Shizuoka Hospital, Juntendo University School of Medicine, Shizuoka 410-2295, Japan.
Shizuoka Medical Research Center for Disaster, Juntendo University, Shizuoka 410-2295, Japan.
Int J Mol Sci. 2025 May 22;26(11):4972. doi: 10.3390/ijms26114972.
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with limited treatment options, and early detection remains challenging due to the lack of reliable non-invasive biomarkers. This study investigated plasma and urine circulating tumor deoxyribonucleic acid (ctDNA) methylation profiles as potential biomarkers for PDAC detection. A total of 35 patients with PDAC and 10 non-cancerous controls were enrolled, and whole-genome bisulfite sequencing was performed on ctDNA extracted from both plasma and urine samples. Plasma ctDNA methylation profiles effectively distinguished cancerous from non-cancerous samples, particularly through differential methylation in intergenic regions. Hierarchical clustering further enabled the accurate grouping of patients with PDAC. However, urine ctDNA did not show significant methylation differences. These findings suggest that plasma ctDNA methylation holds promise as a non-invasive biomarker for PDAC detection, whereas urine ctDNA appears less informative. Future research should validate these findings in larger cohorts and investigate machine learning approaches to improve diagnostic performance, ultimately facilitating earlier detection and improved patient outcomes.
胰腺导管腺癌（PDAC）是一种致命的恶性肿瘤，治疗选择有限，由于缺乏可靠的非侵入性生物标志物，早期检测仍然具有挑战性。本研究调查了血浆和尿液循环肿瘤脱氧核糖核酸（ctDNA）甲基化谱作为PDAC检测的潜在生物标志物。共纳入35例PDAC患者和10例非癌对照，对从血浆和尿液样本中提取的ctDNA进行全基因组亚硫酸氢盐测序。血浆ctDNA甲基化谱能有效区分癌性和非癌性样本，特别是通过基因间区域的差异甲基化。层次聚类进一步实现了对PDAC患者的准确分组。然而，尿液ctDNA未显示出明显的甲基化差异。这些发现表明，血浆ctDNA甲基化有望作为PDAC检测的非侵入性生物标志物，而尿液ctDNA的信息量似乎较少。未来的研究应在更大的队列中验证这些发现，并研究机器学习方法以提高诊断性能，最终促进早期检测并改善患者预后。
