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

doi:10.3969/j.issn.1674-8115.2023.12.011

Abstract

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

CLC Number:

R735

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.

Figures/Tables 1

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References 57

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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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