胃癌患者血清miR-369、miR-1323水平及其临床意义

Serum levels of miR-369 and miR-1323 in gastric cancer patients and their clinical significance

目的分析胃癌患者血清中miR-369与miR-1323的表达水平及其与患者临床病理特征预后的关系。方法选取2016年3月—2018年3月西南医科大学附属医院胃肠外科手术治疗的胃癌患者97例为病例组,根据随访生存情况分为预后良好亚组59例和预后不良亚组38例;另外选择同期医院健康体检者90例作为健康对照组。采用实时荧光定量PCR(qRT-PCR)检测胃癌患者血清miR-369与miR-1323的表达水平;受试者工作特征曲线(ROC)分析miR-369、miR-1323及两者联合对胃癌患者预后的预测价值;采用Kaplan-Meier法分析血清miR-369、miR-1323与胃癌患者预后的关系;Cox回归分析影响胃癌患者预后的危险因素。结果病例组血清miR-369水平低于健康对照组,血清miR-1323水平高于健康对照组(t/P=8.808/<0.001、7.919/<0.001);预后不良亚组患者血清miR-369水平显著低于预后良好亚组,血清miR-1323水平显著高于预后良好亚组(t/P=4.537/<0.001、7.010/<0.001);血清miR-369、miR-1323表达水平与患者癌组织分化程度、肿瘤直径、TNM分期、淋巴结转移、浸润深度有关(miR-369:t/P=5.500/<0.001、4.813/<0.001、2.965/0.004、2.674/0.009、3.276/0.001;miR-1323:2.790/0.006、3.878/<0.001、2.621/0.010、3.605/0.001、3.560/0.001);血清miR-369、miR-1323及二者联合预测胃癌患者预后的AUC为0.704、0.747、0.823,二者联合预测价值大于单独检测(Z/P=2.713/0.006、1.733/0.040);miR-369低、miR-1323高、分化程度低、TNM分期高、淋巴结转移、浸润深度高是胃癌患者预后不良的危险因素[OR(95%CI)=2.256(1.174~4.333)、1.376(1.011~1.872)、1.058(1.007~1.111)、1.288(1.002~1.655)、1.353(1.080~1.695)、1.493(1.029~2.167)]。结论胃癌患者血清miR-369呈低表达,miR-1323呈高表达,二者对于患者预后具有良好的预测价值,是患者预后不良的影响因素。

Objective To analyze the expression levels of miR-369 and miR-1323 in the serum of gastric cancer patients and their relationship with clinical pathological characteristics and prognosis.Methods Ninety-seven gastric cancer patients who underwent Gastrointestinal Surgery at the Affiliated Hospital of Southwest Medical University from March 2016 to March 2018 were selected as the case group.Based on follow-up survival,they were divided into a subgroup of 59 patients with good prognosis and a subgroup of 38 patients with poor prognosis;In addition,90 patients who underwent health examinations at the same hospital during the same period were selected as the health control group.Real time fluorescence quantitative PCR(qRT-PCR)was used to detect the expression levels of miR-369 and miR-1323 in the serum of gastric cancer patients;The predictive value of the combination of miR-369 and miR-1323 in predicting the prognosis of gastric cancer patients by analyzing the receiver operating characteristic curve(ROC);The Kaplan Meier method was used to analyze the relationship between serum miR-369,miR-1323 and prognosis of gastric cancer patients;Cox regression analysis of factors affecting the prognosis of gastric cancer patients.Results The serum miR-369 level in the case group was lower than that in the healthy control group,while the serum miR-1323 level was higher than that in the healthy control group(t/P=8.808/<0.001,7.919/<0.001);The serum miR-369 level in patients with poor prognosis subgroup was significantly lower than that in patients with good prognosis subgroup,and the serum miR-1323 level was significantly higher than that in patients with good prognosis subgroup(t/P=4.537/<0.001,7.010/<0.001);The expression levels of serum miR-369 and miR-1323 are related to the degree of cancer tissue differentiation,tumor diameter,TNM staging,lymph node metastasis,and depth of infiltration in patients(miR-369:t/P=5.500/<0.001,4.813/<0.001,2.965/0.004,2.674/0.009,3.276/0.001;miR-1323:2.790/0.006,3.878/<0.001,2.621/0.010,3.605/0.001,3.560/0.001);The AUC values of serum miR-369,miR-1323,and their combination in predicting the prognosis of gastric cancer patients were 0.704,0.747,and 0.823,respectively.The combined predictive value of the two was greater than that of individual tests(Z/P=2.713/0.006,1.733/0.040);Low miR-369,high miR-1323,low differentiation,high TNM staging,lymph node metastasis,and high infiltration depth are risk factors for poor prognosis in gastric cancer patients[OR(95%CI)=2.256(1.174-4.333),1.376(1.011-1.872),1.058(1.007-1.111),1.288(1.002-1.655),1.353(1.080-1.695),1.493(1.029-2.167)].Conclusion The low expression of miR-369 and high expression of miR-1323 in serum of gastric cancer patients have good predictive value for patient prognosis and are influencing factors for poor prognosis.