Objective To investigate the expression of serum Cystatin SN(CST1)and junctional adhesion molecule 2(JAM2)in non-small cell lung cancer(NSCLC)patients and their diagnostic and prognostic value in NSCLC.Methods One hundred and twelve NSCLC patients admitted to the Oncology Department of the 926th Hospital of the Chinese People's Liberation Army Joint Logistics Support Force from February 2019 to February 2021 were selected as the NSCLC group,60 patients with benign lung diseases were selected as the non NSCLC group,and 60 healthy individuals who underwent physical examinations at the same time in the hospital were selected as the healthy control group.ELISA was used to meas-ure serum CST1JAM2 level.Kaplan-Meier curve was used to compare the prognosis of NSCLC patients with different CST1 and JAM2 expression levels.COX regression was used to analyze the independent risk factors for survival and prognosis of NSCLC patients.The receiver operating characteristic curve was used to analyze the diagnostic value of serum CST1 and JAM2 for NSCLC.Results Compared with the non-NSCLC group and the healthy control group,the serum CST1 level in the NSCLC group was higher,while the serum JAM2 level was lower,and the differences were statistically significant(t/P=57.041/<0.001,54.550/<0.001;31.641/<0.001,30203/<0.001);NSCLC patients with TNM stage Ⅲ and lymph node metas-tasis had higher serum CST1 level and lower serum JAM2 level,and the differences were statistically significant(t/P=8.842/<0.001,10.070/<0.001,18243/<0.001,23.365/<0.001);The 3-year overall survival rates of CST1 high expression sub-group and low expression subgroup were 50.00%(30/60)and 71.15%(37/52),respectively,and the difference between the 2 subgroups was statistically significant(Log Rank x2=5.897,P=0.015);The 3-year survival rates of JAM2 high expression subgroup and low expression subgroup were 72.73%(40/55)and 47.37%(27/57),respectively,the difference between the 2 subgroups was statistically significant(Log Rank x2=7299,P=0.007).Tumor stage Ⅲ,lymph node metastasis and high se-rum CST1 were risk factors for poor prognosis of NSCLC patients,while high serum JAM2 was a protective factor[HR(95%CI)=1.610(1.007-2.505),2263(1.151-6.100),2.522(1.406-4.563),0.557(0.368-0.844)];The AUC of serum CST1,JAM2 and their combination in predicting the prognosis of NSCLC were 0.816,0.862 and 0.924,respectively.The AUC of the combination of the two was greater than that of serum CST1 or JAM2 alone(Z=5.123,4.012,all P<0.001).Conclusion The increase of serum CST1 and decrease of JAM2 in NSCLC patients are related to adverse clinical and pathological pa-rameters.The combination of the two has high diagnostic value for the prognosis of NSCLC and is a serum biomarker for evaluating the prognosis of NSCLC patients.