血清miR-1246、CXCL12和CXCR4水平预测非小细胞肺癌患者术后预后的效能

The efficacy of serum miR-1246,CXCL12 and CXCR4 expression in predicting the prognosis of patients with non-small cell lung cancer after surgery

目的观察血清miR-1246、趋化因子基质细胞衍生因子-1(CXCL12)和CXC趋化因子受体4(CXCR4)在非小细胞肺癌(NSCLC)患者术后预后中的预测价值。方法选择2019年1月至2020年6月在该院手术治疗的98例NSCLC患者为NSCLC组。选择同期该院肺部良性疾病患者75例和健康体检者75例分别纳入肺良性疾病对照组和健康对照组。比较3组血清miR-1246、CXCL12和CXCR4水平,比较不同特征及不同预后NSCLC患者血清miR-1246、CXCL12和CXCR4水平,分析3项指标预测NSCLC术后两年内发生预后不良的效能。结果NSCLC组术前血清miR-1246水平明显低于肺良性疾病对照组和健康对照组,肺良性疾病对照组也明显低于健康对照组,差异有统计学意义(P<0.05)。NSCLC组中,术后miR-1246水平较术前明显升高,差异有统计学意义(P<0.05)。NSCLC组术前血清CXCL12和CXCR4水平较肺良性疾病对照组和健康对照组明显升高,肺良性疾病对照组明显高于健康对照组,差异有统计学意义(P<0.05)。NSCLC组中,术后血清CXCL12和CXCR4水平较术前明显降低,差异有统计学意义(P<0.05)。低分化、Ⅲ+Ⅳ期和有淋巴结转移的NSCLC患者血清miR-1246水平明显低于高中分化、Ⅰ+Ⅱ期和无淋巴结转移的NSCLC患者,差异有统计学意义(P<0.05);而低分化、Ⅲ+Ⅳ期和有淋巴结转移的NSCLC患者血清CXCL12和CXCR4水平明显高于高中分化、Ⅰ+Ⅱ期和无淋巴结转移的NSCLC患者,差异有统计学意义(P<0.05)。预后不良者血清miR-1246水平明显低于预后良好者,而预后不良者血清CXCL12和CXCR4水平明显高于预后良好者,差异有统计学意义(P<0.05)。3项指标联合检测的灵敏度为82.1%,特异度为84.7%,曲线下面积为0.910,其AUC明显高于miR-1246(Z=3.131,P=0.002)、CXCL12(Z=2.998,P=0.003)和CXCR4(Z=3.022,P=0.003)单独检测。结论miR-1246、CXCL12和CXCR4参与了NSCLC的发生、发展过程,联合检测miR-1246、CXCL12和CXCR4预测NSCLC术后两年内发生预后不良具有较高的效能。

Objective To observe the prognostic value of serum miR-1246,chemokine stromal cell-derived factor-1(CXCL12)and CXC chemokine receptor 4(CXCR4)in patients with non-small cell lung cancer(NSCLC).Methods A total of 98 patients with NSCLC who underwent surgical treatment in Zhoupu Hospital of Pudong New Area from January 2019 to June 2020 were selected as the NSCLC group.A total of 75 cases of pulmonary benign disease patients and 75 cases of healthy physical examination people were included in the benign lung disease control group and healthy control group respectively.The serum levels of miR-1246,CXCL12 and CXCR4 in the three groups were compared,and the serum levels of miR-1246,CXCL12 and CXCR4 in NSCLC patients with different characteristics and different prognosis were compared,and the efficacy of the three indexes in predicting poor prognosis in NSCLC within two years after surgery was analyzed.Results The preoperative serum miR-1246 level in NSCLC group before surgery was significantly lower than that in benign lung disease control group and healthy control group,and miR-1246 level in the benign lung disease control group was also lower than that in healthy control group,the differences were statistically significant(P<0.05).In NSCLC group,the level of miR-1246 after surgery was significantly higher than that before surgery,with statistical significance(P<0.05).The levels of serum CXCL12 and CXCR4 in NSCLC group before surgery were significantly higher than those in benign lung disease control group and healthy control group,and the levels in benign lung disease control group were significantly higher than those in healthy control group,the differences were statistically significant(P<0.05).In NSCLC group,the levels of serum CXCL12 and CXCR4 after surgery were significantly lower than those before surgery,the differences were statistically significant(P<0.05).The serum miR-1246 levels of NSCLC patients with low differentiation,stageⅢ+Ⅳand lymph node metastasis were significantly lower than those of patients with high and moderate differentiation,stageⅠ+Ⅱand no lymph node metastasis,the differences were statistically significant(P<0.05).The serum CXCL12 and CXCR4 levels in NSCLC patients with low differentiated,stageⅢ+Ⅳand lymph node metastasis were significantly higher than those in NSCLC patients with high and moderate differentiated,stageⅠ+Ⅱand without lymph node metastasis,the differences were statistically significant(P<0.05).The level of serum miR-1246 in poor prognosis patients was significantly lower than that in good prognosis patients,while the levels of serum CXCL12 and CXCR4 in poor prognosis patients were significantly higher than those in good prognosis patients,the differences were statistically significant(P<0.05).The sensitivity,specificity and area under curve were 82.1%,84.7%and 0.910 respectively.The AUC was significantly higher than that of miR-1246(Z=3.131,P=0.002),CXCL12(Z=2.998,P=0.003)and CXCR4(Z=3.022,P=0.003).Conclusion miR-1246,CXCL12 and CXCR4 are involved in the development and progression of NSCLC,and the combined detection of miR-1246,CXCL12 and CXCR4 has a high efficacy in predicting the occurrence of poor prognosis of NSCLC within two years after surgery.