Value of Plasma Methylated SFRP2 in Prognosis of Gastric Cancer

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.