血清溶血磷脂酶自黏蛋白和溶血磷脂酸对胰腺癌的临床诊断价值

Clinical diagnostic value of serum autotaxin and lysophosphatidic acid in pancreatic cancer

目的探讨血清溶血磷脂酶自黏蛋白(ATX)和溶血磷脂酸(LPA)对胰腺癌患者的临床诊断价值。方法收集2015年1月至2021年5月间北部战区总医院经手术病理确诊的114例胰腺癌患者(胰腺癌组)和94例良性胰腺疾病患者(良性胰腺病组)外周血血清标本,并以120名健康志愿者外周血作为对照组。记录患者的性别、年龄、吸烟史、饮酒史、胰腺癌家族史及肿瘤发生部位、大小、是否发生淋巴结转移、是否出现周围神经浸润等。采用ELISA法检测血清ATX、LPA和CA19-9水平。绘制ATX、LPA单独和(或)联合CA19-9预测胰腺癌临床诊断的受试者工作特征曲线(ROC),计算曲线下面积(AUC),用最大约登指数法确定最佳临界值,计算灵敏度和特异度。结果114例胰腺癌组高糖饮食及吸烟患者分别为54例(47.3%)、60例(52.6%),高于94例良性胰腺病组的15例(16.1%)、11例(11.7%)及120名对照组的24名(20%)、26名(21.7%)。与良性胰腺病组[267.5(184,977)ng/ml、9.83(4.9,28.2)μg/ml、51.2(21,105.3)U/ml]和对照组[255.3(130,1408)ng/ml、10.8(5.2,49)μg/ml、36.3(13,69.1)U/ml]比较,早期及晚期胰腺癌患者血清ATX、LPA和CA19-9水平[294.9(262,1455)ng/ml、15.75(8.3,92)μg/ml、131.1(23,289)U/ml;422(312,1620)ng/ml、24.6(9.5,97.3)μg/ml、217.4(32,970)U/ml]均显著升高,差异有统计学意义(P值均<0.05)。血清ATX预测早期胰腺癌和晚期胰腺癌的AUC值分别为0.71(95%CI 0.52~0.87)、0.92(95%CI 0.81~0.98),约登指数为0.57,临界值为286 ng/ml,灵敏度分别为65.3%、89.6%,特异度均为80.0%;LPA的AUC值为0.75(95%CI 0.67~0.91)、0.95(95%CI 0.89~0.99),约登指数为0.48,临界值为10.7μg/ml,灵敏度分别为80.7%、95.7%,特异度均为69.4%;CA19-9的AUC值为0.82(95%CI 0.71~0.85)、0.86(95%CI 0.78~0.93),约登指数为0.47,临界值为57 U/ml,灵敏度分别为77.3%、82.3%,特异度均为75.0%。与对照组和良性胰腺病组比较,血清ATX联合CA19-9及ATX、LPA联合CA19-9检测对早期胰腺癌诊断的预测效率AUC值均较单独使用CA19-9检测时显著升高,差异有统计学意义(P值均<0.05);而血清ATX联合CA19-9及ATX、LPA联合CA19-9检测对晚期胰腺癌诊断的预测效率AUC值与单独使用CA19-9检测时差异无统计学意义。结论血清LPA、ATX与CA19-9联合检测可提升早期胰腺癌的诊断效率。

Objective To investigate the clinical diagnostic value of autotaxin(ATX)and its product lysophosphatidic acid(LPA)in patients with pancreatic cancer.Methods Peripheral blood samples and related clinical data of 114 patients with pancreatic cancer(pancreatic cancer group)and 94 patients with benign pancreatic disease(benign pancreatic disease group)diagnosed in the Northern Theater General Hospital from January 2015 to May 2021 were collected,and peripheral blood of 120 healthy volunteers was used as control group.Patients′gender,age,smoking history,history of alcohol consumption,family history of pancreatic cancer,tumor site and size,lymph node metastasis or not,peripheral nerve infiltration and the like were all recorded.Serum ATX,LPA and CA19-9 level was detected by ELISA.The receiver operating characteristic curve(ROC)of ATX alone,LPA alone and(or)combined with CA19-9 for the clinical diagnosis of pancreatic cancer was plotted,and the area under the curve(AUC)was calculated.Maximal Youden index method was used to determine the cutoff,and the sensitivity and specificity were calculated.Results There were 54(47.3%)patients with high sugar diet and 60(52.6%)patients with smoking in pancreatic cancer group,which were higher than 15(16.1%)and 11(11.7%)in benign pancreatic disease group,and 24(20%)and 26(21.7%)in control group(n=120).The serum ATX,LPA and CA19-9 of early and advanced pancreatic cancer[294.9(262,1455)ng/ml,15.75(8.3,92)μg/ml and 131.1(23,289)U/ml;422(312,1620)ng/ml,24.6(9.5,97.3)μg/ml and 217.4(32,970)U/ml]were all greatly increased,and all the differences were statistically significant(all P value<0.05).The AUC values of serum ATX for early and advanced pancreatic cancer were 0.71(95%CI 0.52-0.87)and 0.92(95%CI 0.81-0.98),respectively;the Youden index was 0.57,the cutoff was 286 ng/ml,and the sensitivity was 65.3%and 89.6%,respectively;the specificity was 80%.The AUC values of LPA were 0.75(95%CI 0.67-0.91)and 0.95(95%CI 0.89-0.99);the Youden index was 0.48,the cutoff was 10.7μg/ml,and the sensitivity was 80.7%and 95.7%,respectively;the specificity was 69.4%.The AUC values of CA19-9 were 0.82(95%CI 0.71-0.85)and 0.86(95%CI 0.78-0.93);the Youden index was 0.47,the cutoff was 57 U/ml,and the sensitivity was 77.3%and 82.3%,respectively;the specificity was 75.0%.Compared to control group and benign pancreatic disease group,the predictive efficiency of serum ATX+CA19-9 and CA19-9+ATX+LPA for the diagnosis of early pancreatic cancer was significantly higher than that of CA19-9 alone,and the difference was statistically significant(all P value<0.05),while the predictive efficiency of serum ATX+CA19-9 and CA19-9+ATX+LPA for the diagnosis of advanced pancreatic cancer was not significantly different from that of CA19-9 alone.Conclusions The combined detection of serum LPA,ATX and CA19-9 can improve the diagnostic efficiency of early pancreatic cancer.