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Objective Previous studies have shown that the all-cause mortality and non-colorectal cancer mortality of patients with fecal occult blood test(FOBT)positivity are significantly increased,suggesting that FOBT results may have more prognostic value.However,there was no studies reporting the association between the FOBT results and outcomes for GC patients after radical gastrectomy.We aimed to explore the effect of preoperative FOBT results on the short-term efficacy,long-term efficacy and adjuvant chemotherapy efficacy in gastric cancer(GC)patients undergoing radical gastrectomy.Methods Retrospective analysis was performed for GC patients who underwent radical gastrectomy from July 2007 to July 2014.Propensity score matching(PSM)was used to reduce baseline bias,including age,sex,and TNM stage.In addition,paraffinembedded tumor sections from 60 FOBT(+)patients and 60 FOBT(-)patients were selected to evaluate the invasive degree of tumor-associated macrophages(TAMs)and the expression level of proinflammatory cytokines(TNF-α,IL-6)in tumor tissues immunohistochemically.A Cox proportional hazards regression model was used to determine the independent prognostic factors associated with survival.Results A total of 3003 patients were included.A total of 246 patients(8.2%)were FOBT-positive with a worse preoperative status and the tumor stage was more advanced(all p<0.05).There was no significant difference in demographic data between the FOBTpositive group(n=246)and the FOBT-negative group(n=984)after a 1:4 PSM.The overall postoperative complications,anastomotic leakage and major complications were significantly higher in the FOBT-positive group than in the FOBT-negative group.Kaplan-Meier curve analysis showed that the prognosis of the FOBT-positive group was significantly worse than that of the FOBT-negative group(5-year OS: 48.2%vs.58.8%,respectively,p=0.007).Stratified analysis showed that the OS rate of the FOBTpositive group was significantly lower than that of the FOBT-negative group at all pathological stages(5-year OS: p stage I: 82.7%vs.92.1%,p=0.040; p stage Ⅱ: 58.2%vs.75.3%,p=0.039; p stage Ⅲ: 33.5%vs.43.3%,p=0.036)(Fig.1A-D).In addition,in a separate analysis of each clinicopathological factor,the prognostic value of the FOBT result was consistent The multivariate analysis found that FOBT-positivity was an independent risk factor for OS(HR: 1.32,95%CI: 1.085-1.606,p=0.005).The chemotherapy benefit analysis for stage Ⅱ/Ⅲ patients found that the FOBT-negative group benefited from chemotherapy(5-year OS: 49.9%vs.36.8%,p=0.001),whereas none of the FOBT-positive groups benefited(5-year OS: 40.8%vs.37.7%in the chemotherapy and non-chemotherapy groups,respectively,p=0.896).Paraffin-embedded sections of FOBT-negative and FOBT-positive patients(60 cases each)were randomly selected for IHC analysis to explore the association between FOBT results and the tumor immune microenvironment(CD68,IL-6 and TNF-α expression).The CD68,IL-6 and TNF-α expression in tumor cells was significantly higher in FOBT-positive patients than in FOBT-negative patients(all p<0.05).Conclusions In the present study,we found that approximately 8%of GC patients had a preoperative FOBT-positive status.Preoperative FOBT-positivity is associated with postoperative complications and a worse prognosis of GC patients.In addition,FOBTpositivity may be associated with changes in the tumor immune microenvironment.Stage Ⅱ/Ⅲ GC patients with FOBT-positive tumors cannot benefit from chemotherapy alone and may potentially benefit from immunotherapy.Further exploration is warranted.