D-二聚体、糖类抗原199和胰岛素样生长因子结合蛋白2对可切除胰腺癌患者术后监测和生存期预测的价值

Value of D-dimer,carbohydrate antigen 199 and insulin-like growth factor binding protein 2 for postoperative monitoring and survival time prediction in patients with resectable pancreatic cancer

目的评估D-二聚体、糖类抗原199(CA199)和胰岛素样生长因子结合蛋白2(IGFBP2)对可切除胰腺癌患者术后监测和生存期预测的价值。方法收集秦皇岛市第一医院2010年5月至2014年1月收治的可手术切除的119例胰腺癌患者资料。采用胶乳增强免疫比浊法测定患者术前、术后疾病稳定及疾病进展时D-二聚体水平,电化学发光法测定CA199水平,酶联免疫吸附试验测定血清IGFBP2水平。以30名健康体检者和40例胰腺浆液性囊腺瘤患者为对照。分析胰腺癌患者术前D-二聚体、CA199、IGFBP2水平与临床病理特征及生存期间的关系。结果胰腺癌患者术前D-二聚体、CA199、IGFBP2均高于两对照组(均P<0.01)。与术后疾病稳定期相比,胰腺癌患者疾病进展后血清D-二聚体、CA199和IGFBP2水平均升高[1496.0 ng/ml(590.0 ng/ml,2280.4 ng/ml)比578.1 ng/ml(381.7 ng/ml,671.5 ng/ml),207.0 U/ml(54.5 U/ml,736.5 U/ml)比31.9 U/ml(14.1 U/ml,44.0 U/ml),(435±107)ng/ml比(249±83)ng/ml,均P<0.01]。各临床病理因素分层胰腺癌患者间术前D-二聚体水平升高者比例的差异均无统计学意义(均P>0.05);淋巴结转移患者中CA199和IGFBP2水平升高者比例均高于淋巴结未转移患者(均P<0.05),其他因素与二者表达水平是否升高均无关(均P>0.05)。术前D-二聚体水平升高胰腺癌患者无进展生存(PFS)时间和总生存(OS)时间均短于D-二聚体水平正常者[(10.6±1.2)个月比(20.4±2.4)个月,(18.9±1.9)个月比(29.2±2.6)个月,均P<0.01]。当CA199以37 U/ml为分界值时,术前CA199水平与胰腺癌患者生存无相关性(均P>0.05);当分界值分别为253.8 U/ml(入组时CA199中位数)和1000 U/ml时,CA199水平升高者的PFS时间和OS时间均短于CA199水平正常者[253.8 U/ml:(11.5±1.5)个月比(21.0±2.6)个月,(19.9±2.1)个月比(29.0±2.7)个月,均P<0.01;1000 U/ml:(8.9±1.9)个月比(19.1±1.9)个月,(15.5±2.3)个月比(28.0±2.0)个月,均P<0.01]。当IGFBP2以339.1 ng/ml为分界值时,术前IGFBP2水平升高胰腺癌患者PFS时间和OS时间均短于IGFBP2水平正常者[(10.8±1.1)个月比(21.1±2.6)个月,(18.9±1.8)个月比(30.3±2.8)个月,均P<0.01]。Cox多因素分析结果显示,术前D-二聚体、IGFBP2水平是胰腺癌患者PFS和OS的独立影响因素(D-二聚体:HR=0.561,95%CI 0.336~0.936,P=0.027;HR=0.515,95%CI 0.303~0.874,P=0.014;IGFBP2:HR=0.430,95%CI 0.253~0.731,P=0.002;HR=0.361,95%CI 0.202~0.644,P=0.001)。结论对于可切除胰腺癌患者,D-二聚体、CA199和IGFBP2可用于术后病情监测,术前D-二聚体和IGFBP2可用于生存期预测。

Objective To investigate the value of D-dimer,carbohydrate antigen 199(CA199)and insulin-like growth factor binding protein 2(IGFBP2)for postoperative monitoring and prediction of survival time in patients with resectable pancreatic cancer.Methods The data of 119 patients with pancreatic cancer who were admitted to the First Hospital of Qinhuangdao from May 2010 to January 2014 were collected.Immunoturbidimetry was used to determine the level of D-dimer before surgery,at postoperative stable disease stage and disease progression stage;electrochemiluminescence was used to determine the level of CA199,and enzyme-linked immunosorbent assay(ELISA)was used to determine the serum IGFBP2 level.A total of 30 healthy people and 40 patients with pancreatic serous cystadenoma were treated as the controls.The correlations of the levels of preoperative D-dimer,CA199 and IGFBP2 with clinicopathological characteristics and survival time of patients with pancreatic cancer were analyzed.Results The levels of preoperative D-dimer,CA199,IGFBP2 in patients with pancreatic cancer were higher than those in the both control group(all P<0.01).The levels of serum D-dimer,CA199 and IGFBP2 after the progression of pancreatic cancer were higher than those at postoperative stable disease stage[1496.0 ng/ml(590.0 ng/ml,2280.4 ng/ml)vs.578.1 ng/ml(381.7 ng/ml,671.5 ng/ml),207.0 U/ml(54.5 U/ml,736.5 U/ml)vs.31.9 U/ml(14.1 U/ml,44.0 U/ml),(435±107)ng/ml vs.(249±83)ng/ml,all P<0.01].There were no statistical differences in the proportion of pancreatic cancer patients stratified by different clinicopathological factors with the increased levels of D-dimer before operation(all P>0.05).The proportion of the increased levels of CA199 and IGFBP2 in patients with lymph node metastasis was higher than that in patients without lymph node metastasis(both P<0.05);there was no association of the increased levels of CA199 and IGFBP2 with other factors(all P>0.05).The preoperative progression-free survival(PFS)time and overall survival(OS)time of pancreatic cancer patients with elevated D-dimer level was shorter than that for those with normal D-dimer level[(10.6±1.2)months vs.(20.4±2.4)months,(18.9±1.9)months vs.(29.2±2.6)months,both P<0.01].When the threshold value of CA199 was 37 U/ml,there was no correlation between CA199 and survival of pancreatic cancer patients(all P>0.05);when the threshold value was 253.8 U/ml(median CA199 for the enrolled patients)and 1000 U/ml,patients with elevated CA199 level had shorter OS time and PFS time compared with the patients with normal CA199 level[253.8 U/ml:(11.5±1.5)months vs.(21.0±2.6)months,(19.9±2.1)months vs.(29.0±2.7)months,both P<0.01;1000 U/ml:(8.9±1.9)months vs.(19.1±1.9)months,(15.5±2.3)months vs.(28.0±2.0)months,both P<0.01].When the threshold value of IGFBP2 was 339.1 ng/ml,patients with elevated preoperative IGFBP2 level had shorter PFS time and OS time compared with the patients with normal IGFBP2 level[(10.8±1.1)months vs.(21.1±2.6)months,(18.9±1.8)months vs.(30.3±2.8)months,both P<0.01].Cox multivariate analysis showed that preoperative D-dimer and IGFBP2 levels were independent factors affecting PFS and OS in patients with pancreatic cancer(D-dimer:HR=0.561,95%CI 0.336-0.936,P=0.027;HR=0.515,95%CI 0.303-0.874,P=0.014;IGFBP2:HR=0.430,95%CI 0.253-0.731,P=0.002;HR=0.361,95%CI 0.202-0.644,P=0.001).Conclusions For patients with resectable pancreatic cancer,D-dimer,CA199 and IGFBP2 can be used for postoperative condition monitoring,and preoperative D-dimer and IGFBP2 can be used for survival time prediction.