亮氨酸拉链EF-hand结构域跨膜蛋白1、钠氢交换蛋白1和腺苷酸环化酶相关蛋白2在胃癌组织中的表达及对术后复发的预测价值
The expression of leucine zipper EF-hand domain transmembrane protein 1, sodium hydrogen exchange protein 1 and adenylate cyclase related protein 2 in gastric cancer tissues and their predictive value for postoperative recurrence
摘要目的:探讨亮氨酸拉链EF-hand结构域跨膜蛋白1(LETM1)、钠氢交换蛋白1(NHE-1)和腺苷酸环化酶相关蛋白2(CAP2)在胃癌组织中表达及对术后复发的预测价值。方法:回顾性分析海门市人民医院2017年1月至2020年1月92例行外科手术治疗的早期胃癌患者的临床资料。根据术后6个月复发情况分为复发组(16例)和未复发组(76例)。采用实时荧光定量聚合酶链反应法检测手术切除标本的癌组织和癌旁正常组织LETM1、NHE-1和CAP2 mRNA表达水平。采用多因素Logistic回归分析影响胃癌患者术后复发的独立危险因素;绘制受试者工作特征(ROC)曲线,分析LETM1、NHE-1和CAP2 mRNA预测复发的效能。绘制Kaplan-Meier生存曲线,分析不同LETM1、NHE-1和CAP2 mRNA表达水平患者的生存率。结果:癌组织LETM1、NHE-1和CAP2 mRNA均明显高于癌旁组织(0.41±0.12比0.22±0.07、0.85±0.27比0.49±0.15和0.31±0.10比0.19±0.06),差异有统计学意义( P<0.01)。复发组N 1期比例明显高于未复发组[9/16比22.37%(17/76)],差异有统计学意义( P<0.05);复发组癌组织LETM1、NHE-1和CAP2 mRNA明显高于未复发组(0.61±0.20比0.37±0.13、1.24±0.38比0.77±0.21和0.60±0.19比0.25±0.10),差异有统计学意义( P<0.01)。多因素Logistic回归分析结果显示,控制N分期后,LETM1、NHE-1和CAP2 mRNA仍是影响胃癌患者术后复发的独立危险因素( OR = 1.52、3.11和1.21,95% CI 1.26~1.82、2.36~4.09和1.04~1.41, P<0.01)。ROC曲线分析结果显示,LETM1、NHE-1和CAP2 mRNA预测胃癌患者术后复发的曲线下面积(AUC)分别为0.768、0.802和0.850,各指标联合预测胃癌患者术后复发的AUC为0.965。以ROC曲线分析获得的截断值为分界,将患者分为LETM1 mRNA高表达(>0.54,30例)与低表达(≤0.54,62例)、NHE-1 mRNA高表达(>1.09,35例)与低表达(≤1.09,57例)、CAP2 mRNA高表达(>0.49,28例)与低表达(≤0.49,64例)。Kaplan-Meier生存曲线分析结果显示,LETM1、NHE-1和CAP2 mRNA高表达患者生存率明显低于低表达患者(73.33%比98.39%、80.00%比96.49%和78.57%比95.31%),差异有统计学意义( χ2 = 15.08、6.95和6.75, P<0.01)。 结论:LETM1、NHE-1和CAP2 mRNA与早期胃癌术后复发有关,检测三者表达有望为术后复发的预测提供一种新的策略。
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abstractsObjective:To investigate the expression of leucine zipper EF-hand domain transmembrane protein 1 (LETM1), sodium hydrogen exchange protein 1 (NHE-1) and adenylate cyclase related protein 2 (CAP2) in gastric cancer tissues and the predictive value for postoperative recurrence.Methods:The clinical data of 92 patients with early gastric cancer who underwent surgical treatment from January 2017 to January 2020 in Jiangsu Haimen People′s Hospital were retrospectively analyzed. According to the recurrence condition 6 months after operation, the patients were divided into recurrence group (16 cases) and non recurrence group (76 cases). The expression levels of LETM1, NHE-1 and CAP2 mRNA in cancer tissues and adjacent tissues were detected by real time fluorescent quantitative polymerase chain reaction. Multifactor Logistic regression analysis was used to analyze the related influencing factors of postoperative recurrence. The receiver operating characteristic (ROC) curve was drawn, and the effectiveness of LETM1, NHE-1 and CAP2 mRNA in predicting recurrence was analyzed. The Kaplan-Meier survival curve was drawn, and the survival rate was analyzed in patients with different expression levels of LETM1, NHE-1 and CAP2 mRNA.Results:The LETM1, NHE-1 and CAP2 mRNA in cancer tissues were significantly higher than those in adjacent tissues (0.41±0.12 vs. 0.22±0.07, 0.85±0.27 vs. 0.49±0.15 and 0.31±0.10 vs. 0.19±0.06), and there were statistical differences ( P<0.01). The proportion of N 1 stage in recurrent group was significantly higher than that in non recurrent group: 9/16 vs. 22.37% (17/76), and there was statistical difference ( P<0.05); the LETM1, NHE-1 and CAP2 mRNA of cancer tissues in recurrent group were significantly higher than those in non recurrent group (0.61±0.20 vs. 0.37±0.13, 1.24±0.38 vs. 0.77±0.21 and 0.60±0.19 vs. 0.25±0.10), and there were statistical differences ( P<0.01). Multifactor Logistic regression analysis result showed that, after controlled N stages, the LETM1, NHE-1 and CAP2 mRNA were still independent risk factors for postoperative recurrence in patients with gastric cancer ( OR = 1.52, 3.11 and 1.21; 95% CI 1.26 to 1.82, 2.36 to 4.09 and 1.04 to 1.41; P<0.01). ROC curve analysis result showed that the area under the curve (AUC) of LETM1, NHE-1 and CAP2 mRNA for predicting postoperative recurrence in patients with gastric cancer were 0.768, 0.802 and 0.850, respectively. The AUC of combination the indexes for predicting postoperative recurrence in patients with gastric cancer was 0.965. According to the cut-off value of ROC curve, the patients were divided into LETM1 mRNA high expression (>0.54, 30 cases) and low expression (≤0.54, 62 cases), NHE-1 mRNA high expression (>1.09, 35 cases) and low expression (≤1.09, 57 cases), CAP2 mRNA high expression (>0.49, 28 cases) and low expression (≤0.49, 64 cases). Kaplan-Meier survival curve analysis result showed that the survival rates in patients with high expression of LETM1, NHE-1 and CAP2 mRNA were significantly lower than those in patients with low expression (73.33% vs. 98.39%, 80.00% vs. 96.49% and 78.57% vs. 95.31%), and there were statistical differences ( χ2 = 15.08, 6.95 and 6.75, P<0.01). Conclusions:LETM1, NHE-1 and CAP2 mRNA are related to the recurrence of early gastric cancer after surgery. The detection of the 3 markers is expected to provide a new strategy for the prediction of postoperative recurrence.
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