Objective:To investigate the expression of serum human phosphatidylethanolamine-binding protein 4 (hPEBP4) in patients with multiple myeloma (MM) and its clinical significance.Methods:A total of 59 symptomatic MM patients admitted to West Branch of Beijing Chaoyang Hospital from September 2016 to September 2018 were selected as the research objects. According to the CRAB symptoms [elevated serum calcium (C), kidney injury (R), anemia (A), bone lesions (B)], all patients were divided into 2 groups, including the active group of 44 patients with CRAB symptoms, and the response group of 15 patients who achieved at least partial remission after chemotherapy and symptom relief of CRAB. According to the degree of bone lesions (BL), 30 patients with severe bone-related events were grouped as the severe bone lesions (SBL) group, and 14 patients were grouped as the non-severe bone lesions (NSBL) group. According to the revised international prognostic staging system (R-ISS), patients in the active group were divided into three subgroups: stage Ⅰ, stage Ⅱ, and stage Ⅲ, including 26, 11 and 7 patients, respectively. A total of 15 healthy examination people whose gender and age matched those of the patients were treated as the healthy control group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of hPEBP4, tumor necrosis factor ligand superfamily member 14 (LIGHT/TNFSF14) and activin A of patients in different groups. Pearson was used to analyze the relationship of the expressions of multiple factors in the active group. The optimal cut-off value of multiple factors diagnosing MM was determined by using receiver operating characteristic (ROC) curve, and according to the cut-off value, the differences in overall survival (OS) of patients with different stratification were compared.Results:In the active group, the respond group, the healthy control group, the level of hPEBP4 was (1.48±0.64) μg/L, (1.49±0.75) μg/L, (0.31±0.10) μg/L, respectively; the level of LIGHT/TNFSF14 was (169±112) ng/L, (256±132) ng/L, (44±27) ng/L,respectively; the level of activin A was (383±266) ng/L, (223±79) ng/L, (234±85) ng/L, respectively; and the differences were statistically significant (all P<0.05). In the active group, the level of hPEBP4 was (1.06±0.60) μg/L, (1.15±0.50) μg/L, (1.73±0.68) μg/L, respectively in patients with stage R-ISSⅠ, R-ISSⅡ and R-ISS Ⅲ, and the difference was statistically significant ( F=3.287, P=0.032). The level of activin A was (219±55) ng/L, (247±117) ng/L, (450±215) ng/L, respectively among patients in stage R-ISSⅠ, R-ISSⅡ, R-ISS Ⅲ, and the level of activin A in stage R-ISS Ⅲ was higher than that in stage R-ISSⅠand R-ISSⅡ (all P < 0.05). The levels of LIGHT/TNFSF14 and activin A of SBL patients were higher than those of NSBL patients [(174±101) ng/L vs. (98±53) ng/L; (467±238) ng/L vs. (189±71) ng/L, all P < 0.05]. The level of hPEBP4 was positively correlated with the levels of M protein ( r=0.694, P < 0.01) and activin A ( r=0.252, P < 0.01) of IgG patients in the active group. ROC curve analysis showed that the optimal cut-off value of hPEBP4, LIGHT/TNFSF14, activin A diagnosing MM was 1.04 μg/L, 97.0 μg/L, 156.2 ng/L. The median overall survival (OS) time of patients with hPEBP4 >1.04 μg/L and hPEBP4 ≤ 1.04 μg/L was 57 months (95% CI 22-92 months) and not reached, respectively, and the difference was statistically significant ( P < 0.05); while the median OS time of patients with activin A ≥ 156.2 ng/L and activin A < 156.2 ng/L was 61 months (95% CI 24-98 months) and not reached, respectively, and the difference was statistically significant ( P < 0.05). Conclusions:High expression level of hPEBP4 is related with the progression of MM. It is positively related with the level of M protein and negatively with the OS of MM patients. It is suggested that hPEBP4 may be used as an important marker to judge disease progression and tumor burden in MM. LIGHT/TNFSF14 and activin A cooperate with hPEBP4 to participate in the pathological processes of tumor microenvironment of MM.