人附睾蛋白4等肿瘤标志物联合全身骨显像对非小细胞肺癌骨转移的诊断价值

Diagnostic value of human epididymis protein 4 and other serum tumor markers combined with the whole body bone scan in bone metastasis of non-small cell lung cancer

目的研究人附睾蛋白4(HE4)等血清肿瘤标志物联合全身骨显像对非小细胞肺癌(NSCLC)骨转移的诊断价值,分析NSCLC骨转移的骨骼分布特点。方法本研究为队列研究,采取非随机抽样的方法,收集2021年7月至2022年6月于湖北医药学院附属随州医院接受血清肿瘤标志物检测和99mTc-MDP发射型计算机断层成像全身骨显像的NSCLC患者83例为研究对象,根据有无发生骨转移分为骨转移阳性组32例和骨转移阴性组51例。比较2组基础资料(性别、年龄)和血清肿瘤标志物水平[HE4、血清癌胚抗原(CEA)、细胞角质蛋白19片段抗原21-1(CYFRA21-1)、鳞状细胞癌抗原(SCCA)],采用多因素logistic回归分析NSCLC患者发生骨转移的危险因素,绘制受试者工作特征曲线分析血清肿瘤标志物水平对NSCLC患者发生骨转移的诊断价值。结果骨转移阳性组HE4、CEA、CYFRA21-1水平均高于骨转移阴性组,分别为HE4[198.60(141.37,357.99)]μg/L比[94.43(64.36,116.72)]μg/L;CEA[5.17(2.44,47.88)]μg/L比[2.61(1.90,3.96)]μg/L;CYFRA21-1[5.18(3.63,8.78)]μg/L比[2.24(1.60,4.06)]μg/L,差异均有统计学意义(Z值分别为4.74、2.81、3.96,均P<0.05)。HE4、CYFRA21-1升高是NSCLC患者发生骨转移的危险因素(OR=1.007,95%CI:1.001~1.014,P=0.025;OR=1.479,95%CI:1.120~1.953,P=0.006)。血清HE4、CYFRA21-1诊断NSCLC患者发生骨转移的曲线下面积分别为0.816(95%CI:0.716~0.893)、0.809(95%CI:0.707~0.887),当HE4的最佳截断值为136.105μg/L时,敏感度为78.1%,特异度为82.4%;当CYFRA21-1的最佳截断值为2.460μg/L时,敏感度为93.7%,特异度为58.8%;HE4联合CYFRA21-1诊断骨转移的曲线下面积为0.866(95%CI:0.774~0.931),敏感度为90.6%,特异度为72.5%。32个骨转移病例共122个骨转移灶,其中胸部54个(44.3%)、脊柱41个(33.6%)、骨盆14个(11.5%)、四肢骨9个(7.4%)、颅骨4个(3.3%)。结论HE4与CYFRA21-1血清水平对NSCLC骨转移有一定的诊断价值,血清HE4与CYFRA21-1水平检测联合全身骨显像可提高NSCLC骨转移诊断效率。NSCLC骨转移以胸部、脊柱、骨盆为主。

Objective To study the diagnostic value of human epididymis protein 4(HE4)and other serum tumor markers combined with whole body bone scan in bone metastasis of non-small cell lung cancer(NSCLC),and to analyze the bone distribution characteristics of bone metastasis of NSCLC.Methods It was a cohort study involving 83 NSCLC patients selected by a non-random sampling method who received serum tumor marker detection and 99mTc-MDP emission computed tomography for the whole body bone scan in Suizhou Hospital,Hubei University of Medicine from July 2021 to June 2022.They were allocated to bone metastasis positive group(n=32)and bone metastasis negative group(n=51)according to the presence or absence of bone metastases.Baseline characteristics(sex,age)and serum levels of tumor markers,including HE4,carcinoembryonic antigen(CEA),cyto-keratin 19 fragment antigen 21-1(CYFRA21-1)and squamous cell carcinoma antigen(SCCA)between groups were compared.Risk factors for bone metastasis in NSCLC patients were analyzed by multivariate logistic regression,and the diagnostic value of serum tumor marker levels for bone metastasis in NSCLC patients was identified by plotting the receiver operating characteristic(ROC)curves.Results Serum levels of HE4,CEA and CYFRA21-1 in the bone metastasis positive group were significantly higher than those in the bone metastasis negative group,with the results of HE4(198.60[141.37,357.99]μg/L vs 94.43[64.36,116.72]μg/L),CEA(5.17[2.44,47.88]μg/L vs 2.61[1.90,3.96]μg/L),CYFRA21-1(5.18[3.63,8.78]μg/L vs 2.24[1.60,4.06]μg/L),and all differences are statistically significant(Z values were 4.74,2.81 and 3.96,respectively;all P<0.05).Elevated HE4 and CYFRA21-1 were risk factors for bone metastasis in NSCLC patients(OR=1.007,95%CI:1.001-1.014,P=0.025;OR=1.479,95%CI:1.120-1.953,P=0.006).The area under the curve(AUC)of serum HE4 and CYFRA21-1 for diagnosing bone metastasis in NSCLC patients was 0.816(95%CI:0.716-0.893)and 0.809(95%CI:0.707-0.887),respectively.When the optimal cut-off value of serum HE4 level was 136.105μg/L,the sensitivity and specificity in diagnosing bone metastasis in NSCLC patients were 78.1%and 82.4%,respectively.When the optimal cut-off value of serum CYFRA21-1 level was 2.460μg/L,the sensitivity and specificity in diagnosing bone metastasis in NSCLC patients were 93.7%and 58.8%,respectively.The AUC of HE4 combined with CYFRA21-1 for the diagnosis of bone metastasis was 0.866(95%CI:0.774-0.931),the sensitivity and specificity were 90.6%and 72.5%,respectively.There were 122 bone metastases in 32 cases,including 54 in the chest(44.3%),41 in the spine(33.6%),14 in the pelvis(11.5%),9 in the limbs(7.4%),and 4 in the skull(3.3%).Conclusions Serum levels of HE4 and CYFRA21-1 have certain diagnostic value for bone metastasis of NSCLC.The detection of serum levels of HE4 and CYFRA21-1 combined with whole body bone imaging can improve the diagnostic efficiency of bone metastasis of NSCLC.The main bone metastases sites of NSCLC are chest,spine and pelvis.