Clinical utility impact of DNA-based cytology using droplet digital methylation-specific PCR in gastric cancer.

IF 5.1 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gastric Cancer Pub Date : 2025-10-13 DOI:10.1007/s10120-025-01674-y

Hiroki Harada, Takafumi Soeno, Akira Ooki, Kanako Naito, Hiroyuki Minoura, Kota Okuno, Shohei Fujita, Mikiko Sakuraya, Tadashi Higuchi, Koshi Kumagai, Takeshi Naitoh, Yusuke Kumamoto, Naoki Hiki, Keishi Yamashita

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引用次数: 0

Abstract

Background: Peritoneal dissemination is a major cause of poor prognosis in gastric cancer (GC). Although conventional peritoneal lavage cytology (CY) is used to detect micrometastatic peritoneal spread, its sensitivity is limited. This study aimed to evaluate the clinical utility of droplet digital methylation-specific PCR (ddMSP) targeting cancer-specific methylation for DNA-based detection of peritoneal dissemination.

Methods: Peritoneal lavage fluid was prospectively collected from 400 samples in 357 GC patients, including 360 samples from 339 patients with chemotherapy-naïve tumors. DNA was extracted, bisulfite-converted, and analyzed by ddMSP targeting CDO1 and HOPX methylation. Diagnostic performance was assessed by ROC analysis, and associations with clinicopathological features and prognosis were evaluated using logistic and Cox regression models.

Results: CDO1 and HOPX methylation levels were significantly elevated in CY1 cases compared with CY0 (p < 0.0001). CDO1 methylation demonstrated excellent diagnostic accuracy for CY1 (AUC: 0.93; sensitivity: 83.9%; specificity: 90.9%), while HOPX methylation showed slightly lower performance (AUC: 0.86). Multivariate analysis revealed that ddMSP CDO1-hi was independently associated with serosal invasion (pT4), and HOPX-hi with both pT4 and nodal metastasis. Furthermore, CDO1-hi status was an independent adverse prognostic factor for peritoneal dissemination-free survival (HR: 2.73, p = 0.018).

Conclusions: ddMSP-based detection of CDO1 methylation provides a sensitive and specific method for identifying micrometastatic peritoneal spread in GC. This DNA-based approach may serve as a valuable prognostic biomarker and contribute to improved perioperative management in gastric cancer.

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应用微滴数字甲基化特异性PCR检测胃癌dna细胞学的临床应用影响

背景：腹膜播散是胃癌预后不良的主要原因。虽然传统的腹膜灌洗细胞学（CY）用于检测微转移性腹膜扩散，但其敏感性有限。本研究旨在评估针对癌症特异性甲基化的液滴数字甲基化特异性PCR （ddMSP）在基于dna的腹膜传播检测中的临床应用。方法：前瞻性收集357例胃癌患者400份腹膜灌洗液，其中339例chemotherapy-naïve肿瘤患者360份。提取DNA，亚硫酸盐转化，并通过靶向CDO1和HOPX甲基化的ddMSP进行分析。采用ROC分析评估诊断效果，并采用logistic和Cox回归模型评估与临床病理特征和预后的关系。结果：与CY0患者相比，CY1患者CDO1和HOPX甲基化水平显著升高(p)。结论：基于ddmsp检测CDO1甲基化为鉴别GC微转移性腹膜扩散提供了一种敏感、特异的方法。这种基于dna的方法可能作为一种有价值的预后生物标志物，有助于改善胃癌的围手术期管理。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Gastric Cancer 医学-胃肠肝病学

CiteScore

14.70

自引率

2.70%

发文量

审稿时长

6-12 weeks

期刊介绍： Gastric Cancer is an esteemed global forum that focuses on various aspects of gastric cancer research, treatment, and biology worldwide. The journal promotes a diverse range of content, including original articles, case reports, short communications, and technical notes. It also welcomes Letters to the Editor discussing published articles or sharing viewpoints on gastric cancer topics. Review articles are predominantly sought after by the Editor, ensuring comprehensive coverage of the field. With a dedicated and knowledgeable editorial team, the journal is committed to providing exceptional support and ensuring high levels of author satisfaction. In fact, over 90% of published authors have expressed their intent to publish again in our esteemed journal.