Objective:To investigate the expression level of NME3 in gastric cancer and its correlation with clinicopathological characteristics and prognosis.Methods:A retrospective case series study was conducted. The clinicopathological data of 156 patients with gastric cancer who received radical gastrectomy in Zhejiang Cancer Hospital between January 2013 and December 2017 were collected. The samples of cancer tissues and paracancerous tissues were taken and partial paracancerous tissues were not meet the standard. Finally, immunohistochemical staining was conducted on both cancer tissues (156 cases) and paracancerous tissues (139 cases) to detect the expression of NME3 protein; H scoring system was used to score the expression of NME3 protein and the patients were divided into NME3 high expression group (H score ≥ 6 points) and NME3 low expression group (H score < 6 points). The clinicopathological characteristics of the 2 groups were analyzed. Kaplan-Meier method was used for overall survival (OS) analysis of the 2 groups, and log-rank test was used for comparison. Univariate and multivariate Cox proportional risk models were used to determine the poor independent factors affecting the poor OS in patients with gastric cancer.Results:The median age of the 156 patients was 61 years (53 years, 68 years), including 110 males (70.5%) and 46 females (29.5%). The proportion of patients with NME3 high expression in cancer tissues was lower than that in paracancerous tissues [51.9% (81/156) vs. 75.5% (105/139)], and the difference was statistically significant ( χ2 = 17.60, P < 0.001). The proportion of patients with NME3 high expression in moderate-low differentiation and moderate differentiation group was lower than that of those in low-differentiation group [63.3% (50/79) vs. 39.4% (28/71)], the proportion of patients with NME3 high expression in pTNM staging group Ⅲ-Ⅳ was higher than that of those in pTNM staging group Ⅰ-Ⅱ [55.5% (76/137) vs. 26.3% (5/19)], and the difference was statistically significant (both P < 0.05). The proportion of patients with NME3 high expression was 62.2% (46/74), 52.0% (13/25), 39.3% (22/56), respectively in patients with Lauran intestinal type, mixed type and diffused type, and the differences were statistically significant ( χ2 = 6.69, P = 0.035). In addition, OS of patients with the NME3 high expression group was better than that of those with the NME3 low expression group, and the difference was statistically significant ( P < 0.001). The further analysis of gender subgroup showed that OS of male patients with the NME3 high expression group was better than that of those with the NME3 low expression group, and OS of female patients with the NME3 high expression group was better than that of those with the NME3 low expression group, and the differences was statistically significant (all P < 0.05). Univariate and multivariate Cox regression analysis showed that the expression of NME3 in cancer tissues (high expression vs. low expression: HR = 0.342, 95% CI: 0.207-0.564, P < 0.001), family history (yes vs. no: HR = 2.240, 95% CI: 1.285-3.907, P = 0.004), pN staging (N 2-3vs. N 0-1: HR = 2.133, 95% CI: 1.114-4.083, P = 0.022), pM staging (M 1vs. M 0: HR = 2.761, 95% CI: 1.386-5.500, P = 0.004), carcinoma embryonic antigen (CEA) level (CEA > 5 ng/ml vs. CEA ≤ 5 ng/ml: HR = 1.688, 95% CI: 1.018-2.798, P = 0.042), carbohydrate antigen 125 (CA125) level (CA125 > 35 U/ml vs. CA125 ≤ 35 U/ml: HR = 2.913, 95% CI: 1.403-6.047, P = 0.004) were independent factors influencing OS in patients with gastric cancer. Conclusions:NME3 is lowly expressed in gastric cancer tissues, and it is highly expressed in higher-differentially, late staged and intestinal type gastric cancer. NME3 low expression is an independent risk factor for the poor prognosis of gastric cancer. It is speculated that NME3 may play a inhibitory role in gastric cancer.