腹腔灌洗液循环肿瘤DNA在预测胃肠道恶性肿瘤腹膜转移中应用的研究进展

doi:10.3969/j.issn.1674-8115.2023.12.011

上海交通大学学报（医学版） ›› 2023, Vol. 43 ›› Issue (12): 1554-1561.doi: 10.3969/j.issn.1674-8115.2023.12.011

• 综述 • 上一篇

腹腔灌洗液循环肿瘤DNA在预测胃肠道恶性肿瘤腹膜转移中应用的研究进展

白龙(), 夏翔, 曹晖, 张子臻()

上海交通大学医学院附属仁济医院胃肠外科，上海 200127

收稿日期:2023-07-23 接受日期:2023-10-27 出版日期:2023-12-28 发布日期:2024-02-01
通讯作者: 张子臻 E-mail:bailong001001@163.com;zhangzizhen@renji.com
作者简介:白龙（2000—），女，硕士生；电子信箱：bailong001001@163.com。
基金资助:
国家自然科学基金项目(81972206);上海市“医苑新星”青年医学人才培养资助计划(2022-65);上海市卫生健康委员会卫生行业临床研究专项(202140458);上海市自然科学基金项目(22ZR1438800);上海交通大学医学院附属仁济医院培育基金(RJTJ22-MS-025)

Progress in application of peritoneal lavage fluid circulating tumor DNA to predicting peritoneal metastasis of gastrointestinal cancer

BAI Long(), XIA Xiang, CAO Hui, ZHANG Zizhen()

Department of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China

Received:2023-07-23 Accepted:2023-10-27 Online:2023-12-28 Published:2024-02-01
Contact: ZHANG Zizhen E-mail:bailong001001@163.com;zhangzizhen@renji.com
Supported by:
National Natural Science Foundation of China(81972206);Shanghai "Medical Garden Rising Star" Young Medical Talent Training Grant Program(2022-65);Health Industry Clinical Research Project of Shanghai Municipal Health Commission(202140458);Shanghai Natural Science Foundation(22ZR1438800);Cultivation Fund of Renji Hospital, Shanghai Jiao Tong University School of Medicine(RJTJ22-MS-025)

摘要/Abstract

摘要：

腹膜转移是胃肠道恶性肿瘤患者死亡的重要原因之一，也是临床诊治的难点。如何在具有高危因素的患者中预测腹膜转移的发生，将诊治关口前移至腹膜转移发生之前，提高患者的生存获益，是目前临床工作中尚未解决的问题。在细胞学检查阳性率较低、隐匿型腹膜转移诊断困难的情况下，能够早期诊断腹膜转移的分子标志物与检测技术亟待验证。腹腔灌洗液具有较少的白细胞来源的无细胞DNA干扰，相对循环肿瘤DNA（circulating tumor DNA，ctDNA）浓度更高；并且，与原发病灶或潜在腹膜转移灶的直接接触，使其在胃肠道肿瘤的预测中有独特的优势。目前，腹腔灌洗液中ctDNA的检测方式有数字PCR、基于表观遗传的分析方式以及二代测序等。随着技术的迭代，应用二代测序及个性化定制面板进行ctDNA检测，不仅在预测术后腹膜转移方面展现出了极大潜力，更是对腹膜转移进行预防性升阶治疗设想的推动力量。该文对腹腔灌洗液ctDNA在预测胃肠道恶性肿瘤腹膜转移中的应用进行综述。

关键词: 胃肠道恶性肿瘤, 腹膜转移, 腹腔灌洗液, 循环肿瘤DNA

Abstract:

Peritoneal metastasis is one of the important causes of death in patients with gastrointestinal cancer and is also a difficult point in clinical diagnosis and treatment. How to predict the occurrence of peritoneal metastasis in patients with high-risk factors, advance the threshold of diagnosis and treatment before the occurrence of peritoneal metastasis, and improve the survival benefit of patients is an unsolved problem in clinical work. In the case of low positive rate of cytology and difficulty in diagnosing occult peritoneal metastasis, new molecular markers and detection techniques for early diagnosis of peritoneal metastasis need to be verified. Peritoneal lavage fluid has the characteristics of less leukocyte-derived cell-free DNA interference, higher concentration of circulating tumor DNA (ctDNA), and direct contact with the primary lesion or potential peritoneal metastasis at physical distance, making it a unique advantage in gastrointestinal cancer. At present, the detection methods of ctDNA in peritoneal lavage fluid include digital PCR, epigenetic-based analysis, and next-generation sequencing. With the iteration of technology, the application of next-generation sequencing and personalized panels to ctDNA detection has not only shown great potential in predicting postoperative peritoneal metastasis, but also promoted the idea of preventive escalation treatment of peritoneal metastasis. This article reviews the current application of ctDNA to peritoneal lavage fluid in predicting peritoneal metastasis of gastrointestinal cancer.

Key words: gastrointestinal cancer, peritoneal metastasis, peritoneal lavage fluid, circulating tumor DNA

中图分类号:

R735

白龙, 夏翔, 曹晖, 张子臻. 腹腔灌洗液循环肿瘤DNA在预测胃肠道恶性肿瘤腹膜转移中应用的研究进展[J]. 上海交通大学学报（医学版）, 2023, 43(12): 1554-1561.

BAI Long, XIA Xiang, CAO Hui, ZHANG Zizhen. Progress in application of peritoneal lavage fluid circulating tumor DNA to predicting peritoneal metastasis of gastrointestinal cancer[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(12): 1554-1561.

图/表 1

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Literature	No. of patients	Detecting technique	Target site of DNA	Positive result in PLF/%(n)	Prediction of peritoneal recurrence
HIRAKI^[45]	80	Real-time methylation-specific PCR	CHFR, E-cadherin, BNIP3	19% (6/31)^①	2 of 5 patients with multigene methylation showed peritoneal recurrence after surgery
HIRAKI^[46]	107	Real-time methylation-specific PCR	BNIP3,CHFR,CYP1B1,MINT25,RASSF2,SFRP2	20% (9/45)^②	3 of 9 patients carrying positive methylation experienced peritoneal recurrence
YU^[47]	92	Real-time methylation-specific PCR	CDH1 methylation	48.9% (45/92)	CDH1 methylation correlated significantly with distant metastasis (P<0.005)
HAN^[48]	92	Real-time methylation-specific PCR	Methylated MINT2	90.2% (37/41)	Levels of methylated MINT2 DNA in PLF was significantly different between patients with and without peritoneal metastasis (P<0.000 1)
YU^[49]	92	Real-time methylation-specific PCR	TIMP-3 methylation	53.3% (49/92)	TIMP-3 hypermethylation in PLF (γ=0.804, P<0.001) was closely correlated with positive PLF cytology
HU^[50]	92	Quantitative methylation-specific PCR	Methylated THBS1	58.7% (54/92)	Accuracy 63.0% (34/54), Sensitivity 87.2% (34/39), Specificity 100% (34/34)

Literature	No. of patients	Detecting technique	Target site of DNA	Positive result in PLF/%(n)	Prediction of peritoneal recurrence
HIRAKI^[45]	80	Real-time methylation-specific PCR	CHFR, E-cadherin, BNIP3	19% (6/31)^①	2 of 5 patients with multigene methylation showed peritoneal recurrence after surgery
HIRAKI^[46]	107	Real-time methylation-specific PCR	BNIP3,CHFR,CYP1B1,MINT25,RASSF2,SFRP2	20% (9/45)^②	3 of 9 patients carrying positive methylation experienced peritoneal recurrence
YU^[47]	92	Real-time methylation-specific PCR	CDH1 methylation	48.9% (45/92)	CDH1 methylation correlated significantly with distant metastasis (P<0.005)
HAN^[48]	92	Real-time methylation-specific PCR	Methylated MINT2	90.2% (37/41)	Levels of methylated MINT2 DNA in PLF was significantly different between patients with and without peritoneal metastasis (P<0.000 1)
YU^[49]	92	Real-time methylation-specific PCR	TIMP-3 methylation	53.3% (49/92)	TIMP-3 hypermethylation in PLF (γ=0.804, P<0.001) was closely correlated with positive PLF cytology
HU^[50]	92	Quantitative methylation-specific PCR	Methylated THBS1	58.7% (54/92)	Accuracy 63.0% (34/54), Sensitivity 87.2% (34/39), Specificity 100% (34/34)

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腹腔灌洗液循环肿瘤DNA在预测胃肠道恶性肿瘤腹膜转移中应用的研究进展

Progress in application of peritoneal lavage fluid circulating tumor DNA to predicting peritoneal metastasis of gastrointestinal cancer

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