摘要目的:探讨母体胚胎亮氨酸拉链激酶(MELK)在胃癌组织表达及与患者临床病理特征和预后的关系。方法:选取郑州大学附属肿瘤医院2021年1月至2023年6月收治的53例胃癌患者[男23例，女30例；年龄(58.69±12.04)岁；淋巴结转移情况：淋巴结转移28例，未淋巴结转移患者25例；中高分化患者30例，低分化患者23例；Ⅰ～Ⅱ期21例，Ⅲ～Ⅳ期32例；年龄>60岁患者20例，<60岁患者33例；肿瘤直径>5 cm患者29例，<5 cm患者24例]的胃癌组织作为研究对象，癌旁组织作为对照研究。采用蛋白质组学分析胃癌中差异表达的基因。采用荧光定量聚合酶链反应和蛋白质免疫印迹分析癌旁组织和胃癌组织MELK mRNA和蛋白质表达水平。分析MELK蛋白表达变化与胃癌患者临床病理特征关系。采用多因素Logistic回归法分析胃癌预后不良的主要因素；以MELK蛋白表达水平为阈值，将胃癌组织分为高表达组和低表达组，采用Kaplan Meier曲线分析高表达组和低表达组患者3年生存情况。采用免疫组织化学分析细胞核增殖抗原(Ki-67)蛋白表达水平；组间计量数据比较采用 t检验。 结果:蛋白质组学发现癌旁组织和胃癌组织有398个差异表达蛋白，其中上调蛋白218个，下调蛋白180个，上调蛋白中MELK上调最为显著。癌旁组织MELK mRNA和蛋白表达水平(1.00±0.11、0.52±0.11)低于胃癌组织(1.59±0.17、1.02±0.29)，差异有统计学意义( t＝21.180，11.710， P<0.05)。淋巴结转移胃癌患者MELK蛋白表达水平(1.24±0.27)高于未淋巴结转移患者(0.82±0.12)，差异有统计学意义( t＝7.548， P<0.05)。低分化胃癌患者MELK蛋白表达水平(1.21±0.23)高于中高分化患者(0.88±0.25)，差异有统计学意义( t＝5.058， P<0.05)。Ⅲ～Ⅳ期胃癌患者MELK蛋白表达水平(1.18±0.25)高于Ⅰ～Ⅱ期患者(0.89±0.26)，差异有统计学意义( t＝3.387， P<0.05)。Ki-67阳性患者胃癌组织MELK表达水平(1.12±0.27)高于低表达组患者(0.74±0.09)，差异有统计学意义( t＝4.878， P<0.05)。高表达组3年生存期[(16.63±3.98)个月]低于低表达组[(34.26±4.52)个月]，差异有统计学意义(Log-rank＝3.485， P<0.05)。胃癌患者淋巴结转移、TNM分期、细胞分化程度、MELK水平是导致胃癌患者预后不良的危险因素( P<0.05)。 结论:MELK在胃癌组织中高表达，与患者临床分期、转移、分化程度和增殖呈正相关，表达水平越高患者预后不良越差。

abstractsObjective:To investigate the expression of maternal embryo leucine zipper kinase (MELK) in gastric cancer tissues and its relationship with clinicopathological features and prognosis of patients.Methods:A total of 53 patients with gastric cancer [23 male and 30 female patients; the average age was (58.69±12.04) years old; 28 patients had lymph node metastasis and 25 patients did not; 30 patients with moderately and highly differentiated tumors and 23 patients with poorly differentiated tumors; 21 patients in stage Ⅰ-Ⅱ and 32 patients in stage Ⅲ-Ⅳ; among them, 20 patients were over 60 years old and 33 patients were under 60 years old; 29 patients had a tumor diameter over 5 cm and 24 patients had a tumor diameter under 5 cm] admitted to Affiliated Cancer Hospital of Zhengzhou University from January 2021 to June 2023 were selected as the research subjects, with adjacent tissues as the control group. The differentially expressed genes in gastric cancer were analyzed by proteomics, and MELK was found to be significantly different. The mRNA and protein expression levels of MELK in adjacent tissues and gastric cancer tissues were analyzed by fluorescence quantitative polymerase chain reaction and protein immunoblotting. The relationship between the expression of MELK protein and clinicopathological features of gastric cancer patients was analyzed. The main factors affecting the prognosis of gastric cancer patients were analyzed by multivariate Logistic regression analysis. The patients were divided into high expression group and low expression group according to the expression level of MELK protein, and the 3-year survival rate of the two groups was analyzed by Kaplan-Meier curve. The expression level of proliferation cell nuclear antigen (Ki-67) was analyzed by immunohistochemistry. Quantitative data between groups were compared by t test. Results:The proteomics showed that there were 398 differentially expressed proteins between adjacent tissues and gastric cancer tissues, including 218 upregulated proteins and 180 downregulated proteins. Among the upregulated proteins, the most significant upregulation was observed for maternal fetal leucine zipper kinase, so it was selected as the protein of interest for this study. The mRNA and protein expression levels of maternal fetal leucine zipper kinase in adjacent tissues were significantly lower than those in gastric cancer tissues (1.00±0.11 vs. 1.59±0.17, 0.52±0.11 vs. 1.02±0.29, t=21.180, 11.710, P<0.05). The protein expression level of maternal fetal leucine zipper kinase in lymph node metastasis gastric cancer patients (1.24±0.27) was significantly higher than that in patients without lymph node metastasis (0.82±0.12, t=7.548, P<0.05). The protein expression level of maternal fetal leucine zipper kinase in low-differentiated gastric cancer patients (1.21±0.23) was significantly higher than that in patients with intermediate-high differentiation (0.88±0.25, t=5.058, P<0.05). The protein expression level of maternal fetal leucine zipper kinase in stage III-IV gastric cancer patients (1.18±0.25) was significantly higher than that in stage Ⅰ-Ⅱ patients (0.89±0.26, t=3.387, P<0.05). The correlation analysis between maternal fetal leucine zipper kinase and Ki-67 showed that of the 53 gastric cancer patients, the positive rate of Ki-67 was 75.47% (40/53) and the negative rate was 24.52% (13/53). The expression level of maternal embryonic leucine zipper kinase in gastric cancer tissues of Ki-67 positive patients (1.12±0.27) was significantly higher than that of low expression group patients (0.74±0.09, t=4.878, P<0.05). The 3-year survival period of the high expression group [(16.63±3.98) months] was significantly shorter than that of the low expression group [(34.26±4.52) months, Log-rank=3.485, P<0.05]. Lymph node metastasis, TNM staging, cell differentiation degree, and maternal embryonic LZK level were the risk factors for poor prognosis of gastric cancer patients ( P<0.05). Conclusion:Fetal leucine zipper kinase is highly expressed in gastric cancer tissues, and it is positively correlated with clinical staging, metastasis, differentiation degree, and proliferation. The higher the expression level, the worse the prognosis of the patient.