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 / 肿瘤研究与临床

ABSTRACT

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 [1 496.0 ng/ml (590.0 ng/ml, 2 280.4 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 1 000 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; 1 000 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.