NME3在胃癌中的表达及临床意义

Expression of NME3 in gastric cancer and its clinical significance

目的探讨NME3在胃癌中的表达情况及其与临床病理特征、预后等的相关性。方法回顾性病例系列研究。收集2013年1月至2017年12月在浙江省肿瘤医院行胃癌根治术的156例胃癌患者临床病理资料。取癌组织及癌旁组织标本,部分癌旁组织未符合要求,最终对156例癌组织和139例癌旁组织采用免疫组织化学染色检测NME3蛋白表达情况,采用H评分系统对NME3蛋白表达水平进行评分,以6分为临界值,区分NME3蛋白高表达(H评分≥6分)和低表达(H评分<6分)。按照癌组织中NME3蛋白高、低表达,将患者分为NME3高表达组和低表达组。分析两组临床病理特征差异;采用Kaplan-Meier法对两组进行总生存(OS)分析,比较采用log-rank检验。采用单因素、多因素Cox比例风险模型确定影响胃癌患者OS不良的独立影响因素。结果156例患者中位年龄[M(Q 1,Q 3)]为61岁(53岁,68岁),其中男性110例(70.5%),女性46例(29.5%)。癌组织NME3高表达患者比例低于癌旁组织[51.9%(81/156)比75.5%(105/139)],差异有统计学意义(χ^(2)=17.60,P<0.001)。中-低分化+中分化患者癌组织NME3高表达患者比例高于低分化患者[63.3%(50/79)比39.4%(28/71)],pTNM分期Ⅲ~Ⅳ期高于Ⅰ~Ⅱ期[55.5%(76/137)比26.3%(5/19)],差异均有统计学意义(均P<0.05);Lauran分型肠型、混合型、弥漫型患者中癌组织NME3高表达患者比例分别为62.2%(46/74)、52.0%(13/25)、39.3%(22/56),差异有统计学意义(χ^(2)=6.69,P=0.035)。NME3高表达组患者OS优于低表达组,差异有统计学意义(P<0.001);男性和女性患者中NME3高表达组患者OS均优于低表达组,差异均有统计学意义(P<0.05)。单因素、多因素Cox回归分析显示,NME3在癌组织中的表达(高表达比低表达:HR=0.342,95%CI:0.207~0.564,P<0.001)、肿瘤家族史(有比无,HR=2.240,95%CI:1.285~3.907,P=0.004),pN分期(N_(2~3)期比N_(0~1)期,HR=2.133,95%CI:1.114~4.083,P=0.022),pM分期(M_(1)期比M_(0)期,HR=2.761,95%CI:1.386~5.500,P=0.004),癌胚抗原(CEA)水平(>5 ng/ml比≤5 ng/ml,HR=1.688,95%CI:1.018~2.798,P=0.042),糖类抗原125(CA125)水平(>35 U/ml比≤35 U/ml,HR=2.913,95%CI:1.403~6.047,P=0.004)是胃癌患者OS不良的独立影响因素。结论NME3在胃癌组织中低表达,其在分化程度较高、分期晚以及肠型胃癌中具有更高的表达水平,且NME3低表达是胃癌预后不良的独立危险因素,推测NME3在胃癌中可能发挥肿瘤抑制作用。

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(χ^(2)=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 groupⅢ-Ⅳwas higher than that of those in pTNM staging groupⅠ-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(χ^(2)=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_(2-3)vs.N_(0-1):HR=2.133,95%CI:1.114-4.083,P=0.022),pM staging(M_(1)vs.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.