血清肿瘤标志物与矽肺疾病严重程度的关系

摘要

目的 分析矽肺患者血清肿瘤标志物的水平及与疾病严重程度的关系.方法 回顾性研究,选择2012年1月至2015年12月在南京市胸科医院收治矽肺患者160例,另选择健康志愿者160 名作为对照组.化学免疫发光法检测血清和肺泡灌洗液中肿瘤标志物的含量,同时检测患者肺功能参数、血气分析和血清乳酸脱氢酶(LDH)含量.免疫组化染色检测1例矽肺患者肺组织中糖链抗原125(CA125)、糖链抗原19-9(CA19-9)和神经元特异性烯醇化酶(NSE)的表达.组间比较采用Student′s t检验或Mann-Whitney U检验,相关性分析采用直线相关分析.结果 矽肺患者血清中NSE、CA125和CA19-9水平显高于健康对照组[(34.47±13.30)μg/L和(10.24±7.20)μg/L,t=20.27, P<0.000 1;(33.96±17.80)kU/L和(12.23±15.30)kU/L, t=11.71, P<0.000 1;(4.68±5.67)kU/L和(2.78±3.45)kU/L,t=3.67,P<0.002].矽肺患者血清中CA125和CA19-9水平与第1秒用力呼出量(FVE1)、第1秒用力呼出量/用力肺活量(FVE1/FVC)、一氧化碳弥散量(Dlco)和肺总量(TLC)呈负相关(r=-0.423,P=0.001;r=-0.323,P=0.011;r=-0.479,P=0.001;r=-0.285,P=0.043)和(r=-0.324,P=0.022;r=-0.256,P=0.023;r=-0.354,P=0.013;r=-0.356,P=0.012),与血清LDH呈正相关(r=0.378,P=0.001和r=0.347,P=0.21);NSE水平与肺功能参数(Dlco 和 TLC)呈负相关(r=-0.374,P=0.004和r=-0.368,P=0.002),与血清LDH呈正相关(r=0.404,P=0.001).NSE和CA19-9在肺泡灌洗液中的含量高于其在血清中的含量[(39.32±29.30)μg/L和(25.7±12.12)μg/L,t=2.15,P=0.036;(21.36±12.11)kU/L和(11.28±10.78)kU/L, t=2.64,P=0.012].矽肺患者血清中NSE和CA19-9在大容量肺灌洗术后分别降低[(39.20±10.24)μg/L和(15.32±8.35)μg/L,t=8.02,P<0.05;(26.24±12.23 kU/L)和(18.84±5.64)kU/L,t=2.46,P<0.05].矽肺患者肺组织中NSE和CA19-9呈阳性表达,而CA125未见阳性表达.结论 矽肺患者血清中NSE、CA125 和CA19-9的水平明显增高,通过检测血清中NSE、CA125 和CA19-9的水平可以预测矽肺疾病的严重程度.%Objective To investigate the relationship between serum tumor markers and the severity of silicosis.Methods Retrospective study.Total of 160 patients with silicosis were included in the study, and 160 healthy volunteers were recruited as the control group.Tumor marker levels in both bronchoalveolar lavage fluid(BALF)and serum were detected by the immunochemiluminecence methods.The pulmonary function parameters, blood gas analysis and lactate dehydrogenase(LDH)were also analyzed.Lung tissue obtained by a patient with silicosis was stained by neuron specific enolase(NSE), carbohydrate antigen125(CA125) and carbohydrate antigen19-9(CA19-9).Results Serum NSE, CA125 and CA19-9 levels were significantly higher in cases than those in controls[(34.47±13.30)μg/L vs(10.24±7.20)μg/L,t=20.27, P<0.000 1;(33.96±17.80)kU/L vs(12.23±15.30)kU/L, t=11.71, P<0.000 1;(4.68±5.67)kU/L vs(2.78±3.45)kU/L,t=3.67,P<0.002].Significant negative correlations were found between values of tumor markers(CA125 and CA19-9) and spirometric parameters,such as forced expiratory volume in one second %(FVE1%), forced expiratory volume in one second/forced vital capacity(FVE1/FVC), carbon monoxide diffusion capacity (Dlco) and total lung capacity(TLC) (r=-0.423,P=0.001;r=-0.323,P=0.011;r=-0.479,P=0.001;r=-0.285,P=0.043) and (r=-0.324,P=0.022;r=-0.256,P=0.023;r=-0.354,P=0.013;r=-0.356,P=0.012).Significant positive correlations were also observed between values of these tumor markers and LDH(r=0.378,P=0.001 and r=0.347,P=0.21).Significant negative correlations were found between NSE and Dlco and TLC(r=-0.374,P=0.004 and r=-0.368,P=0.002).Significant positive correlations were also observed between NSE and LDH(r=0.404,P=0.001).The NSE and CA19-9 levels in BALF were significantly higher than those in serum[(39.32±29.30)μg/L vs(25.7±12.12)μg/L,t=2.15,P=0.036;(21.36±12.11)kU/L vs(11.28±10.78)kU/L, t=2.64,P=0.012].Patients experienced a decrease in NSE and CA19-9 concentrations following whole lung lavage[(39.20±10.24)μg/L vs(15.32±8.35)μg/L,t=8.02,P<0.05;(26.24±12.23)kU/L vs(18.84±5.64)kU/L,t=2.46,P<0.05].Immunohistochemical studies showed positive NSE and CA19-9 staining in lung biopsy specimen.Conclusion Elevated serum tumor markers including NSE, CA125 and CA19-9 would provide valuable clinical information to assess disease severity in silicosis.