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.