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Value of Plasma Methylated SFRP2 in Prognosis of Gastric Cancer

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Abstract

Background

Secreted frizzled-related protein 2 (SFRP2) in circulating tumor DNA (ctDNA) is related to gastric cancer (GC) proliferation. However, whether methylated SFRP2 in ctDNA serves as the biomarker in GC patients remains unknown.

Aims

To investigate the relationship between methylated SFRP2 and the clinical outcomes of GC patients.

Methods

One hundred and forty-eight GC patients receiving systemic chemotherapy were collected during 2015–2017. Aberrant SFRP2 methylation was detected before and after chemotherapy by digital PCR-based technologies.

Results

Baseline SFRP2 methylation positively correlated with lymph node status (P < 0.001), distant metastasis (P < 0.001) and TNM stage (P = 0.005). The top 50% methylated SFRP2 had shorter progression-free survival (PFS) and overall survival (OS) than those with bottom 50% in stage III GC patients (median PFS, 11.0 vs. NR months; HR 13.05; 95% CI 3.05–55.95; median OS 17.0 vs. NR months; HR 7.80; 95% CI 1.81–33.60) and stage IV GC patients (median PFS, 4.0 vs. 7.0 months; HR 2.74; 95% CI 1.58–4.78; median OS 12.0 vs. 16.0 months; HR 3.14; 95% CI 1.67–5.92). Besides, the increased methylated SFPR2 from baseline to post-treatment was related to the worse PFS and OS among stage IV patients (median PFS, 5.0 vs. 7.0 months; HR 2.17; 95% CI 1.25–3.76; median OS 12.0 vs. 15.5 months; HR 3.51; 95% CI 1.94–6.35), but not to stage III patients.

Conclusions

SFRP2 methylation and dynamic change are associated with GC prognosis. Our findings provide potential biomarker detection approach in ctDNA for prognosis prediction and dynamic monitoring among GC patients.

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Funding

This study was supported by the grants from key Program of the Changzhou Commission of Health (ZD201709, to Dr. Haijiao Yan), and the Young Talents of the Changzhou Commission of Health (QN201902, to Dr. Xiaodong Li).

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Author notes

  1. Haijiao Yan and Wenyu Chen contributed equally to this study.

Authors and Affiliations

  1. Oncology Department, Third Affiliated Hospital of Soochow University, Changzhou, 213003, People’s Republic of China

    Haijiao Yan, Wenyu Chen, Kele Ge, Xizheng Mao, Xiaodong Li & Jun Wu

  2. Hepatobiliary Surgery Department, Third Affiliated Hospital of Soochow University, Changzhou, 213003, People’s Republic of China

    Wensong Liu

Authors
  1. Haijiao Yan
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  2. Wenyu Chen
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  3. Kele Ge
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  4. Xizheng Mao
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  5. Xiaodong Li
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  6. Wensong Liu
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  7. Jun Wu
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Contributions

HY, WC, JW designed the experiments. HY, WC, KG, XM, XL, WL, JW performed the experiments. HY, WC, KG analyzed the data, HY and WC wrote the manuscript. JW supervised the study.

Corresponding author

Correspondence to Jun Wu.

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The authors declared that they have no conflict of interest.

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Yan, H., Chen, W., Ge, K. et al. Value of Plasma Methylated SFRP2 in Prognosis of Gastric Cancer. Dig Dis Sci 66, 3854–3861 (2021). https://doi.org/10.1007/s10620-020-06710-8

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  • DOI: https://doi.org/10.1007/s10620-020-06710-8

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