D-二聚体在女性恶性肿瘤病情监测中的应用价值
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摘要
目的初步探讨D-二聚体对判断女性恶性肿瘤病情和疗效观察的应用价值与诊断效能。方法选取2016年3月—2017年12月间在佛山第一人民医院乳腺肿瘤内科住院治疗的女性恶性肿瘤患者149例,早期术后患者(术后组)58例,晚期复发转移患者(晚期组)91例,测定其接受化疗前后的血浆D-二聚体水平(分别记作D1、D2),分析D-二聚体浓度变化(ΔD=D2-D1)与疗效的相关性。D-二聚体浓度(ng/mL)用中位数(四分位间距)表示,治疗前后配对样本比较用Wilcoxon秩和检验,两组间独立+样本比较用Mann-Whitney U检验,以Spearman法分析两组资料的相关性是否有统计学意义。结果术后组患者化疗后D-二聚体水平低于化疗前(ΔD=-184.8,P<0.0001),D1、D2均与年龄正相关(P<0.01),r~2分别为0.356,0.389。晚期组患者中,化疗后有33例出现病情进展(progressive disease, PD组),58例获得疾病缓解或稳定(非PD组)。PD组化疗前基线水平高于非PD组(1 586 vs 754.2,P<0.01),接受化疗后PD组D-二聚体较基线水平升高(ΔD=1 124,P<0.0001),非PD组较基线水平下降(ΔD=-153.3,P=0.004 5),PD组化疗后D-二聚体水平高于非PD组(2 511 vs 525.8,P<0.01)。以ΔD、D1、D2诊断是否PD分别进行受试者工作特征曲线(receiver operating characteristic curve,ROC)分析,结果显示ROC曲线下面积分别为0.8 603(95%CI:0.768 5～0.952 0)、0.674 0(95%CI:0.558 2～0.759 7)、0.895 6(95%CI:0.829 1～0.962 1),对诊断PD有一定准确性。当ΔD<-145.4 ng/mL、D1>1 375 ng/mL、D2>1 033 ng/mL时,Youden指数最大,诊断PD的准确性较高。结论血浆D-二聚体的变化与肿瘤负荷密切相关,有助于女性恶性肿瘤病情的判断和疗效观察及评价预后,对辅助判断病情进展上的具有较高的诊断效能。
Objective To investigate the clinical significance and diagnostic value of plasma D-dimer measurement in response evaluation of female patients with tumor.Methods 149 female cancer patients were enrolled, in which there were 58 post-operative early staged cases(post-operative group), 91 metastatic cases(metastatic group). D-dimer levels before chemotherapy(D1) and after the last cycle of chemotherapy(D2) were assessed and analyzed to examine whether they are correlated to response of therapy. D-dimer levels were presented as median(25~(th) percentile,75~(th) percentile) and compared using Wilcoxon signed-rank test(for paired samples) and Mann-Whitney U test(for independent samples). Spearman rank tests were conducted to show the correlation of two variables. Results In post-operative group,D2 was lower than D1(ΔD=-184.8,P<0.0001),and both of D1 and D2 were positively correlated with age(r~2= 0.356,0.389,respectively,P<0.01). In metastatic group, after chemotherapy,33 cases had progressive diseases(PD group), while 58 cases gained response or stable diseases(non-PD group). Baseline D-dimer level of PD group was higher than that of non-PD group(1586 vs 754.2,P<0.01),and after chemotherapy the case was similar(2511 vs 525.8,P<0.01). After chemotherapy, D-dimer level increased in PD group(ΔD=1124,P<0.0001), and decreased in non-PD group(ΔD=-153.3,P=0.0045).We compared the abilities of the ΔD(ΔD=D2-D1), D1 and D2 to discriminate between responders and non-responders using receiver operating characteristic curves(ROC). The areas under the curve(AUC) of the ΔD, D1 and D2, were 0.8603(95%CI:0.7685-0.9520)、0.6740(95%CI:0.5582-0.7597)、0.8956(95%CI:0.8291-0.9621), respectively. The appropriate cut-off values with biggest Youden index of D-dimer for non-responders were as follows: ΔD<-145.4 ng/mL,D1>1375 ng/mL,D2>1033 ng/mL. Conclusion Plasma D-dimer level is strongly associated with tumor burden. D-dimer could be used to predict prognosis and treatment response in female patients with tumor.
Objective To investigate the clinical significance and diagnostic value of plasma D-dimer measurement in response evaluation of female patients with tumor.Methods 149 female cancer patients were enrolled, in which there were 58 post-operative early staged cases(post-operative group), 91 metastatic cases(metastatic group). D-dimer levels before chemotherapy(D1) and after the last cycle of chemotherapy(D2) were assessed and analyzed to examine whether they are correlated to response of therapy. D-dimer levels were presented as median(25~(th) percentile,75~(th) percentile) and compared using Wilcoxon signed-rank test(for paired samples) and Mann-Whitney U test(for independent samples). Spearman rank tests were conducted to show the correlation of two variables. Results In post-operative group,D2 was lower than D1(ΔD=-184.8,P<0.0001),and both of D1 and D2 were positively correlated with age(r~2= 0.356,0.389,respectively,P<0.01). In metastatic group, after chemotherapy,33 cases had progressive diseases(PD group), while 58 cases gained response or stable diseases(non-PD group). Baseline D-dimer level of PD group was higher than that of non-PD group(1586 vs 754.2,P<0.01),and after chemotherapy the case was similar(2511 vs 525.8,P<0.01). After chemotherapy, D-dimer level increased in PD group(ΔD=1124,P<0.0001), and decreased in non-PD group(ΔD=-153.3,P=0.0045).We compared the abilities of the ΔD(ΔD=D2-D1), D1 and D2 to discriminate between responders and non-responders using receiver operating characteristic curves(ROC). The areas under the curve(AUC) of the ΔD, D1 and D2, were 0.8603(95%CI:0.7685-0.9520)、0.6740(95%CI:0.5582-0.7597)、0.8956(95%CI:0.8291-0.9621), respectively. The appropriate cut-off values with biggest Youden index of D-dimer for non-responders were as follows: ΔD<-145.4 ng/mL,D1>1375 ng/mL,D2>1033 ng/mL. Conclusion Plasma D-dimer level is strongly associated with tumor burden. D-dimer could be used to predict prognosis and treatment response in female patients with tumor.
引文
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[14] YU J, LI D, LEI D, et al. Tumor-Specific D-Dimer Concentration Ranges and Influencing Factors: A Cross-Sectional Study[J]. PLoS One, 2016, 11(11): e0165390.
[15] LI W, TANG Y, SONG Y, et al. Prognostic role of pretreatment plasma d-dimer in patients with solid tumors: a systematic review and meta-analysis[J]. Cell Physiol Biochem,2018,45(4):1663-1676.
[2] PIKE B, BASSAM A, DIMAK S, et al. Thoughts about thromboembolic events prophylaxis in cancer patients [J]. Magy Onkol, 2011,55(3):164-169.
[3] FALANGA A, MARCHETTI M, RUSSO L. The mechanisms of cancer-associated thrombosis [J]. Thromb Res, 2015, 135 (Suppl. 1):S8-S11.
[4] WANG Y, WANG Z. Predictive value of plasma D-dimer levels in patients with advanced non-small-cell lung cancer[J]. Onco Targets Ther, 2015,8:805-808.
[5] AY C, DUNKLER D, PIRKER R, et al. High D-dimer levels are associated with poor prognosis in cancer patients[J]. Haematologica, 2012, 97(8):1158-1164.
[6] CHEN Y, YU H, WU C,et al. Prognostic value of plasma D-dimer levels in patients with small-cell lung cancer[J]. Biomed Pharmacother,2016,(81):210-217.
[7] GRIVENNIKOV S I, GRETEN F R, KARIN M. Immunity, inflammation, and cancer[J]. Cell,2010,140(6):883-99.
[8] NASH G F, WALSH D C, KAKKAR A K. The role of the coagulation system in tumour angiogenesis[J]. Lancet Oncol,2001, 2(10):608- 613.
[9] 冯红蕾,崔林,李泽,等. 乳腺癌患者血浆D-二聚体水平与临床病理特征的关系[J]. 山东医药,2014,54(42):8-10.
[10] ZHANG X, RAN Y. Prognostic role of elevated platelet count in patients with lung cancer:a systematic review and meta-analysis[J]. Int J Clin Exp Med, 2015, 8(4):5379-5387.
[11] JAVADINIA S A, GHOLAMI A, JOUDI MASHHAD M, et al. Anti-tumoral effects of low molecular weight heparins: a focus on the treatment of esophageal cancer[J]. J Cell Physiol, 2018,233(10):6523- 6529:.
[12] Franchini M, Mannucci P M. Low-molecular-weight heparins and cancer: focus on antitumoral effect[J]. Ann Med,2015,47(2):116-21.
[13] 彭吉芳,乐丽霞,扈新爱,等. 健康人血浆D-二聚体正常参考值调查分析[J]. 临床和实验医学杂志,2012,11(8):626- 628.
[14] YU J, LI D, LEI D, et al. Tumor-Specific D-Dimer Concentration Ranges and Influencing Factors: A Cross-Sectional Study[J]. PLoS One, 2016, 11(11): e0165390.
[15] LI W, TANG Y, SONG Y, et al. Prognostic role of pretreatment plasma d-dimer in patients with solid tumors: a systematic review and meta-analysis[J]. Cell Physiol Biochem,2018,45(4):1663-1676.