胃癌患者血清circ⁃PVT1和miR⁃423⁃5p的水平变化及其与淋巴结转移的关系

Changes of serum circ-PVT1 and miR-423-5p levels in patients with gastric cancer and their relationship with lymph node metastasis

目的探究胃癌(GC)患者血清环状RNA circ-PVT1和miR-423-5p的水平变化及其与淋巴结转移的关系。方法选取2020年6月至2022年6月湖州市第一人民医院收治的GC患者100例,根据治疗后淋巴结转移情况分为转移组(64例)和未转移组(36例)。取同期胃炎、胃溃疡、胃息肉等患者100例作为良性病变组,同期体检健康者100例作为健康人对照组。采用qRT-PCR检测各组血清circ-PVT1、miR-423-5p水平,分析血清circ-PVT1、miR-423-5p水平与GC患者治疗后淋巴结转移的关系;Logistic回归分析GC患者治疗后淋巴结转移的影响因素;ROC曲线分析血清circ-PVT1、miR-423-5p水平对GC患者治疗后淋巴结转移的预测价值。结果与健康人对照组相比,良性病变组和GC组患者血清circ-PVT1水平(1.04±0.30 vs 1.47±0.39 vs 1.83±0.54)显著上调,miR-423-5p水平(1.02±0.28 vs 0.85±0.20 vs 0.51±0.14)显著下降(F分别为87.933、146.594,P<0.05);与良性病变组相比,GC组患者血清circ-PVT1水平显著上调,miR-423-5p水平显著下降。血清circ-PVT1、miR-423-5p水平单独及二者联合诊断GC的ROC曲线下面积(AUC^(ROC))分别为0.729、0.817、0.869,其中二者联合检测的AUC^(ROC)显著高于单独检测(Z分别为3.211、2.133,P<0.05)。与淋巴结未转移组相比,淋巴结转移组GC患者血清circ-PVT1水平(1.66±0.51 vs 1.92±0.58)显著上调,miR-423-5p水平(0.74±0.22 vs 0.38±0.16)显著下降(P<0.05)。Logistic回归分析结果显示,肿瘤直径、分化程度、TNM分期、高水平circ-PVT1是GC患者治疗后淋巴结转移的独立危险因素(P<0.05),高水平miR-423-5p是GC患者治疗后淋巴结转移的独立保护因素(P<0.05)。ROC曲线结果显示,血清circ-PVT1、miR-423-5p水平单独及二者联合预测GC患者淋巴结转移的AUC^(ROC)分别为0.707、0.753、0.841,二者联合预测AUC^(ROC)显著高于单独预测(Z分别为3.595、5.167,P<0.05)。circ-PVT1和miR-423-5p存在靶向关系,且GC患者血清circ-PVT1水平与miR-423-5p水平呈显著负相关(r=-0.546,P<0.05)。结论GC患者血清circ-PVT1水平升高,miR-423-5p水平降低,且均与GC治疗后淋巴结转移密切相关,二者联合对GC治疗后淋巴结转移有较高的预测价值。

Objective To investigate the changes of serum circ-PVT1 and miR-423-5p levels in patients with gastric cancer(GC)and their relationship with lymph node metastasis.Methods One hundred GC patients treated in our hospital from June 2020 to June 2022 were selected.According to the status of lymph node metastasis after treatment,they were further divided into the metastasis group(n=64)and non-metastasis group(n=36).In addition,100 patients with benign lesions such as gastritis,gastric ulcer,and gastric polyp and 100 healthy individuals undergoing physical examination(control)at the same period were selected.The expression levels of serum circ-PVT1 and miR-423-5p were detected by qRT-PCR,and their relationship to lymph node metastasis after GC treatment was analyzed.Logistic regression analysis was used to analyze the influencing factors of lymph node metastasis after GC treatment.The predictive value of serum circ-PVT1 and miR-423-5p levels on lymph node metastasis after GC treatment was analyzed by the receiver operating characteristic(ROC)curve.Results Compared with the control group,serum circ-PVT1 levels in the benign lesion group and GC group(1.04±0.30 vs 1.47±0.39 vs 1.83±0.54)were significantly up-regulated,while serum miR-423-5p levels(1.02±0.28 vs 0.85±0.20 vs 0.51±0.14)were significantly decreased.Compared with the benign lesion group,serum circ-PVT1 levels in the GC group were significantly up-regulated,and serum miR-423-5p levels were significantly decreased(F=87.933 and 146.594,P<0.05).The areas under the ROC curve(AUC^(ROC))of serum circ-PVT1,miR-423-5p,and their combination in the diagnosis of GC were 0.729,0.817,and 0.869,respectively,and the AUCROC of their combination was significantly higher than their individual AUC^(ROC)(Z=3.211 and 2.133,P<0.05).Compared with the GC patients without lymph node metastasis,serum circ-PVT1 levels in the patients with lymph node metastasis were significantly up-regulated(1.66±0.51 vs 1.92±0.58),while serum miR-423-5p levels were significantly decreased(0.74±0.22 vs 0.38±0.16,P<0.05).Logistic regression analysis showed that tumor diameter,differentiation degree,TNM stage,and high levels of serum circ-PVT1 were independent risk factors for the lymph node metastasis of GC patients after treatment(P<0.05)and that high levels of serum miR-423-5p was an independent protective factor(P<0.05).The ROC curve analysis showed that the AUC^(ROC)of serum circ-PVT1,miR-423-5p and their combination in the prediction of lymph node metastasis of GC patients were 0.707,0.753,and 0.841,respectively,and the AUC^(ROC)of their combination was obviously higher than their individual AUC^(ROC)(Z=3.595 and 5.167,P<0.05).There was a target relationship between circ-PVT1 and miR-423-5p.Pearson correlation analysis showed that the levels of serum circ-PVT1 in GC patients were significantly negatively correlated with that of serum miR-423-5p(r=-0.546,P<0.05).Conclusion The levels of serum circ-PVT1 in GC patients are increased and the levels of serum miR-423-5p are decreased.Both of them are closely related to the lymph node metastasis of GC patients after treatment.The combination of the two has a high predictive value for the lymph node metastasis of GC patients after treatment.