血清糖类抗原125和细胞骨架相关蛋白4及鳞状上皮细胞癌抗原对特发性肺间质纤维化患者肺癌的诊断价值

Values of serum carbohydrate antigen 125,cytoskeleton-associated protein 4 and squamous cell carcinoma antigen to the diagnosis of lung cancer in patients with idiopathic pulmonary fibrosis

目的 观察特发性肺间质纤维化(IPF)合并肺癌患者血清糖类抗原125(CA125)、细胞骨架相关蛋白4(CKAP4)、鳞状上皮细胞癌抗原(SCCA)水平变化,探讨三者在IPF患者发生肺癌诊断中的价值。方法 2018年2月—2022年11月河南省胸科医院诊治IPF合并肺癌患者31例为观察组,同期诊治IPF未合并肺癌患者185例为对照组。采集2组空腹静脉血,采用化学发光免疫法检测血清CA125、SCCA水平,采用ELISA法检测血清CKAP4水平。比较观察组与对照组性别比例、年龄、体质量指数、吸烟史、合并症(高血压、糖尿病)及血清CA125、SCCA、CKAP4水平;采用多因素logistic回归分析IPF患者发生肺癌的影响因素;绘制ROC曲线,评估血清CA125、CKAP4、SCCA诊断IPF患者发生肺癌的效能。将观察组患者根据肺癌临床分期分为Ⅰ~Ⅱ期组7例,Ⅲ期组15例,Ⅳ期组9例,比较3组血清CA125、SCCA、CKAP4水平。结果 (1)观察组年龄[(59.46±12.15)岁]大于对照组[(149.67±9.48)岁](P<0.05),男性比率(80.64%)、有吸烟史比率(74.19%)及血清CA125[(48.45±9.82)u/mL]、CKAP4[(546.33±113.62)ng/L]、SCCA[(6.69±1.24)μg/L]水平均高于对照组[(49.67±9.48)岁、58.92%、35.14%、(38.69±7.51)u/mL、(415.27±100.58)ng/L、(5.35±0.94)μg/L](P<0.05),体质量指数及合并高血压、糖尿病比率与对照组比较差异均无统计学意义(P>0.05)。(2)血清CA125(OR=3.803,95%CI:1.756~8.238,P<0.001)、CKAP4(OR=4.178,95%CI:2.534~6.887,P<0.001)、SCCA(OR=4.229,95%CI:2.142~8.349,P<0.001)是IPF患者发生肺癌的影响因素。(3)血清CA125、CKAP4、SCCA分别以44.71 u/mL、452.04 ng/L、6.08μg/L为最佳截断值,诊断IPF患者发生肺癌的AUC分别为0.790(95%CI:0.730~0.843,P<0.001)、0.799(95%CI:0.739~0.850,P<0.001)、0.822(95%CI:0.764~0.870,P<0.001),灵敏度分别为74.20%、83.90%、74.20%,特异度分别为78.90%、62.70%、78.90%;三者联合诊断IPF患者发生肺癌的AUC为0.932(95%CI:0.889~0.961,P<0.001),灵敏度为80.60%,特异度为93.00%。(4)Ⅳ期组血清CA125[(60.32±11.84)u/mL]、CKAP4[(639.56±123.94)ng/L]、SCCA[(8.17±1.45)μg/L]水平均高于Ⅲ期组[(45.68±9.74)u/mL、(549.22±116.47)ng/L、(6.35±1.22)μg/L]、Ⅰ~Ⅱ期组[(39.12±7.40)u/mL、(420.56±94.25)ng/L、(5.51±1.01)μg/L](P<0.05),Ⅲ期组均高于Ⅰ~Ⅱ期组(P<0.05)。结论 IPF合并肺癌患者血清CA125、CKAP4、SCCA水平升高,且增高程度与肺癌分期有关,三者联合对IPF患者发生肺癌有较高的诊断价值。

Objective To investigate the changes of serum carbohydrate antigen 125(CA125),cytoskeleton-associated protein 4(CKAP4)and squamous cell carcinoma antigen(SCCA)levels in patients with idiopathic pulmonary fibrosis(IPF)combined with lung cancer,and to investigate their values to the diagnosis of lung cancer.Methods From February 2018 to November 2022,31 patients with IPF-combined with lung cancer(observation group)and 185 patients with IPF without lung cancer(control group)were collected the fasting elbow venous blood to detect the serum levels of CA125 and SCCA by chemiluminescence immunoassay and to detect the serum level of CKAP4 by ELISA in Henan Provincial Chest Hospital.The gender ratio,age,body mass index,smoking habits,comorbidities(hypertension,diabetes),and the serum levels of CA125,SCCA and CKAP4 were compared between two groups.The influencing factors of lung cancer in IPF patients were analyzed by multivariate logistic regression.ROC curve was plotted to evaluate the efficiencies of serum CA125,CKAP4 and SCCA on the diagnosis of lung cancer in IPF patients.According to clinical stage,observation group was divided into stageⅠ~Ⅱgroup(n=7),stageⅢgroup(n=15)and stageⅣgroup(n=9),and the serum levels of CA125,SCCA and CKAP4 were compared among three groups.Results(1)The patients were older in observation group[(59.46±12.15)years]than those in control group[(49.67±9.48)years],the male ratio,the proportion of smoking habits,and the levels of serum CA125,CKAP4 and SCCA were higher in observation group[80.65%,74.19%,(48.45±9.82)μ/mL,(546.33±113.62)ng/L,(6.69±1.24)μg/L]than those in control group[58.92%,35.14%,(38.69±7.51)μ/mL,(415.27±100.58)ng/L,(5.35±0.94)μg/L](P<0.05),andtherewere no significant differences in the body mass index and proportions of comorbidities(hypertension,diabetes)between two groups(P>0.05).(2)The serum CA125(OR=3.803,95%CI:1.756-8.238,P<0.001),CKAP4(OR=4.178,95%CI:2.534-6.887,P<0.001),and SCCA(OR=4.229,95%CI:2.142-8.349,P<0.001)were the influencing factor of lung cancer in IPF patients.(3)When the optimal cutoff values of serum CA125,CKAP4 and SCCA were 44.71μ/mL,452.04 ng/L and 6.08μg/L,the AUCs for diagnosing lung cancer in IPF patients were 0.790(95%CI:0.730-0.843,P<0.001),0.799(95%CI:0.739-0.850,P<0.001)and0.822(95%CI:0.764-0.870,P<0.001),the sensitivities were 74.20%,83.90%and 74.20%,and the specificities were 78.90%,62.70%and 78.90%,respectively.The AUC of the combined detection of them three for diagnosing lung cancer was 0.932(95%CI:0.889-0.961,P<0.001),the sensitivity was 80.60%,and the specificity was 93.00%.(4)The serum levels of CA125,CKAP4and SCCAwere higher in stageⅣgroup[(60.32±11.84)μ/mL,(639.56±123.94)ng/L,(8.17±1.45)μg/L]than those in stageⅢgroup[(45.68±9.74)μ/mL,(549.22±116.47)ng/L,(6.35±1.22)μg/L]and stageⅠ~Ⅱgroup[(39.12±7.40)μ/mL,(420.56±94.25)ng/L,(5.51±1.01)μg/L](P<0.05),and higher in stageⅢgroup than those in stageⅠ~Ⅱgroup(P<0.05).Conclusion The levels of serum CA125,CKAP4 and SCCA significantly increase in patients with IPF complicated with lung cancer,the severity of IPF is correlated with the stage of lung cancer,and the combined detection of them three has a high value to the diagnosis of lung cancer in IPF patients.