卵巢癌患者血液NLR,CA125,HE4水平联合检测的实验诊断和预后价值研究

Experimental Diagnosis and Prognostic Value of Combined Detection of Blood NLR,CA125 and HE4 Levels in Ovarian Cancer Patients

目的探讨中性粒细胞/淋巴细胞比值(neutrophil-to-lymphocyte ratio,NLR)、血清糖类抗原125(carbohydrate antigen 125,CA125)、血清人附睾蛋白4(human epididymis protein 4,HE4)在卵巢癌(Ovarian Cancer,OC)中的表达水平以及卵巢恶性肿瘤风险判定(risk of ovarian malignancy algorithm,ROMA)比值在OC中的诊断价值及疗效评估的临床意义。方法收集苏州大学附属第三医院2017年5月~2020年2月确诊的OC患者、卵巢良性疾病患者和健康体检者血清,检测各组受试者血液NLR,CA125,HE4以及ROMA比值的水平,比较各组表达水平的差异,评价检测指标在OC及相关疾病诊断中的敏感度和特异度。结果OC组NLR[3.62(1.22,13.11)vs 2.11(1.03,4.81)vs 1.60(0.85 vs 2.98)],CA125[420.80(10.75,4.22)vs 15.47(3.69,173.40)vs 13.81(6.02,56.47)],HE4[203.85(40.11,1500)vs 42.37(31.72,63.81)vs 42.22(23.61,102.40)]水平与良性疾病组和健康对照组相比,差异均具有统计学意义(χ^(2)=60.22,81.31,93.23,均P<0.0001);NLR,CA125对OC诊断的敏感度高于HE4(82.8%,81.0%vs 70.7%),但特异度低于HE4(68.9%,88.7%vs 100.0%),HE4和ROMA比值对OC的诊断特异度最高;相关性分析显示NLR与OC患者的肿瘤数量、患者年龄、TNM分期显著相关(Z=2.338,P=0.019;Z=2.971,P=0.003;Z=2.819,P=0.005);CA125和HE4的表达与OC患者的肿瘤数量、TNM分期、盆腔有无黏液显著相关(Z=2.759,4.228,3.418;2.419,3.767,2.122,均P<0.05);CA125,HE4和NLR术后水平与术前水平相比显著降低,差异有统计学意义(Z=5.365,P<0.001;Z=2.222,P=0.026;Z=4.487,P<0.001)。CA125与HE4的联合检测,结合ROMA比值,具有更好的诊断效率,与NLR比值在OC诊疗中具有互补性。结论NLR联合血清CA125和HE4检测以及ROMA比值可提高OC诊断价值、在OC患者的病情评估及治疗效果中有积极意义。

Objective To investigate the neutrophil-lymphocyte ratio(NLR),serum carbohydrate antigen 125(CA125),human epididymis protein 4(HE4)in ovarian cancer(OC).The diagnostic value and clinical significance of the risk of ovarian malignant tumor analysis(ROMA)ratio in OC.Methods Serum samples of patients with OC with ovarian diseases and healthy people were collected in the Third Hospital Affiliated to Soochow University from May 2017 to February 2020.The levels of NLR,CA125,HE4 and ROMA ratio in blood of each group were detected,and the difference of expression level in each group were compared.The sensitivity and specificity of detection indexes in the diagnosis of OC and related disease were evaluated.Results OC group NLR[3.62(1.22,13.11),2.11(1.03,4.81)vs 1.60(0.85 vs 2.96)],CA125[420.80(10.75,4.22)vs 15.47(3.69,173.40)vs 13.81(6.02,56.47)],HE4[203.85(40.11,1500)vs 42.37(31.72,63.81)vs 42.22(23.61,102.40)]levels compared with benign disease group and health control group,the differences were statistically significant(χ^(2)=60.22,81.31,93.23,all P<0.0001).The sensitivity of CA125 to the diagnosis of OC was higher than that of HE4(81.0%vs 70.7%),but its specificity was lower than that of HE4(88.7%vs 100.0%),and HE4 and ROMA had the highest diagnostic specificity for OC.Correlation analysis showed that NLR was significantly correlated with tumor number,age and TNM stage of OC patients(Z=2.338,P=0.019;Z=2.971,P=0.003;Z=2.819,P=0.005).The expressions of CA125 and HE4 were significantly correlated with tumor number,TNM stage,and pelvic mucus(Z=2.759,4.228,3.418;2.419,3.767,2.122,all P<0.05),Postoperative levels of CA125,HE4,NLR was significantly lower than the preoperative level,and the difference was statistically significant(Z=5.365,P<0.001;Z=2.222,P=0.026;Z=4.487,P<0.001).The combined detection of CA125 and HE4,combined with ROMA ratio,had better diagnostic efficiency and was complementary with NLR ratio in OC diagnosis and treatment.Conclusion NLR combined with serum CA125,HE4 detection and ROMA ratio can improve the diagnostic value of OC and have positive significance in the evaluation of the condition and treatment effect of OC patients.