血清HE4、NSE、CYFRA21-1检测在肺癌诊断及淋巴结转移监测中的价值
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摘要
目的:应用Logistic回归和ROC曲线探讨血清人附睾分泌蛋白4(humanepididymis 4,HE4)、神经元特异度烯醇化酶(neuron specific enolase,NSE)、细胞角蛋白-19片段(cytokerantin-19-fragment,CYFRA21-1)在肺癌诊断和淋巴结转移监测中的意义。方法:采用电化学发光法(electrochemiluminescence)分别检测88例肺癌患者(均经病理确诊)及50例健康对照者血清中的HE4、NSE、CYFRA21-1水平;比较肺癌淋巴结转移与否的HE4、NSE、CYFRA21-1水平变化,并行Logistic回归分析,应用受试者工作特征曲线(receiver operating characteristic curve,ROC)分析HE4、NSE、CYFRA21-1水平对淋巴结转移的意义。结果:肺癌有淋巴结转移组HE4、NSE、CYFRA21-1水平高于无淋巴结转移组,差异有统计学意义(P <0. 05)。经Logistic回归分析,肿瘤大小、病理类型、浸润深度、TNM分期、NSE和CYFRA21-1水平是影响肺癌淋巴结转移的独立危险因素。ROC曲线分析HE4、NSE、CYFRA21-1在肺癌淋巴结转移与否两组中的水平变化:HE4的曲线下面积(area under the curve,AUC)为0. 832,P=0. 000,95%CI:0. 777～0. 921; NSE的AUC为0. 726,P=0. 000,95%CI:0. 686～0. 817; CYFRA21-1的AUC为0. 810,P=0. 000,95%CI:0. 737～0. 907。当HE4的截断值为168. 5 pg/L、NSE的截断值为52. 6μg/L、CYFRA21-1的截断值为26. 4μg/L时,其肺癌淋巴结转移的预测价值最佳。结论:检测血清中HE4、NSE、CYFRA21-1对肺癌诊断及淋巴结转移的监测有重要参考价值,同时借助Logistic回归和ROC曲线分析可为临床治疗提供更有价值的帮助。
Objective: To study the significance of serum humanepididymis 4( HE4),neuron specific enolase( NSE) and cytokerantin-19-fragment( CYFRA21-1) levels in lung cancer patients with lung cancer diagnosis and lymph nodes metastasis by Logistic regression and receiver operating characteristic( ROC) curve analysis. Methods: Electrochemiluminescence method was used to detect serum HE4,NSE and CYFRA21-1 levels in both 88 diagnosed lung cancer patients and 50 healthy controls. Serum HE4,NSE and CYFRA21-1 levels among lung cancer patients with different lymph node metastasis were compared. Logistic regression and ROC cure analysis were conducted to explore the clinical significance of serum HE4,NSE and CYFRA21-1 levels for lymph node metastasis in lung cancer patients. Results: The serum HE4,NSE and CYFRA21-1 levels in lung cancer patients with lymph node metastasis were significantly higher than those without lymph node metastasis( P < 0. 05). Logistic regression analysis showed that tumor size,pathological type,depth of invasion,TNM stage,NSE and CYFRA21-1 levels were independent risk factors for lymph node metastasis occurs in lung cancer. The results from ROC cure analysis showed that the area under the curve( AUC) value of HE4,NSE and CYFRA2 1-1 were 0. 832( P = 0. 000,95% CI: 0. 777～ 0. 921),0. 726( P = 0. 000,95% CI: 0. 686 ～ 0. 817) and 0. 810( P = 0. 000,95% CI: 0. 737 ～ 0. 907) respectively. HE4 at threshold of 168. 5 pg/L,NSE at threshold of 52. 6 μg/L and CYFRA21-1 at threshold of 26. 4 μg/L have the best predictive value on lymph node metastasis occurs in lung cancer. Conclusion: Serum HE4,NSE and CYFRA21-1 levels have important value in diagnosing lung cancer and monitoring lymph node metastasis,it can provide more valuable help for clinical treatment of lung cancer by Logistic regression and ROC curve analysis.
Objective: To study the significance of serum humanepididymis 4( HE4),neuron specific enolase( NSE) and cytokerantin-19-fragment( CYFRA21-1) levels in lung cancer patients with lung cancer diagnosis and lymph nodes metastasis by Logistic regression and receiver operating characteristic( ROC) curve analysis. Methods: Electrochemiluminescence method was used to detect serum HE4,NSE and CYFRA21-1 levels in both 88 diagnosed lung cancer patients and 50 healthy controls. Serum HE4,NSE and CYFRA21-1 levels among lung cancer patients with different lymph node metastasis were compared. Logistic regression and ROC cure analysis were conducted to explore the clinical significance of serum HE4,NSE and CYFRA21-1 levels for lymph node metastasis in lung cancer patients. Results: The serum HE4,NSE and CYFRA21-1 levels in lung cancer patients with lymph node metastasis were significantly higher than those without lymph node metastasis( P < 0. 05). Logistic regression analysis showed that tumor size,pathological type,depth of invasion,TNM stage,NSE and CYFRA21-1 levels were independent risk factors for lymph node metastasis occurs in lung cancer. The results from ROC cure analysis showed that the area under the curve( AUC) value of HE4,NSE and CYFRA2 1-1 were 0. 832( P = 0. 000,95% CI: 0. 777～ 0. 921),0. 726( P = 0. 000,95% CI: 0. 686 ～ 0. 817) and 0. 810( P = 0. 000,95% CI: 0. 737 ～ 0. 907) respectively. HE4 at threshold of 168. 5 pg/L,NSE at threshold of 52. 6 μg/L and CYFRA21-1 at threshold of 26. 4 μg/L have the best predictive value on lymph node metastasis occurs in lung cancer. Conclusion: Serum HE4,NSE and CYFRA21-1 levels have important value in diagnosing lung cancer and monitoring lymph node metastasis,it can provide more valuable help for clinical treatment of lung cancer by Logistic regression and ROC curve analysis.
引文
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[13]Tang YX,Luo CH,Wang Y,et al.Expression of human epididymis protein 4 in cancer and its clinical progress[J].Anti-tumor Pharmacy,2015,5(2):87-91.[唐雨曦,罗晨辉,王瑛,等.人附睾蛋白4(HE4)在恶性肿瘤中的表达与临床进展[J].肿瘤药学,2015,5(2):87-91.]
[14]Liu LH,Luo JX,Xu YJ,et al.Comparison of serue CYFRA21-1,NSE and CEA,levels in patients with different patholgical types of lung cancer[J].Medical ournal of Wuhan University,2015,36(4):533-540.[刘连红,罗建祥,徐月君,等.不同病理类型肺癌患者血清肿瘤标志物CYFRA21-1、NSE和CEA水平的比较[J].武汉大学学报(医学版),2015,36(4):533-540.]
[15]Sun ZM.To evaluate the value of CYFRA21-1,CEA and NSE in the diagnosis of lung cancer[J].China Continuing Medical Education,2017,9(3):52-53.[孙种梅.CYFRA21-1、CEA、NSE在肺癌诊断中的价值[J].中国继续医学教育,2017,9(3):52-53.]
[16]Iwahori K,Suzuki H,Kishi Y,et al.Serum HE4 as a diagnostic and prognostic marker fo lung cancer[J].Tumour Biol,2012,33(4):1141-1149.
[17]Wang X,Fan Y,Wang J,et al.Evaluating the expression and diagnostia value of human epididymis protein 4(HE4)in small cell lung cancer[J].Tumour Biol,2014,35(7):6847-6853.
[2]Chen WQ,Zheng RS,Baade PD,et al.Cancer statistics in China,2015[J].CA Cancer J Clin,2016,66(2):115-132.
[3]Wang Ying,Li Peizhang,Huang Lingsha,et al.Significance of combining expression of serum HE4 and CA153 in predicting lymph node metastasis of early stage breast cancer[J].Modern Oncology,2017,25(11):1737-1739.[王英,李佩章,黄玲莎,等.HE4和CA153联合表达在预测早期乳腺癌淋巴结转移中的意义[J].现代肿瘤医学,2017,25(11):1737-1739.]
[4]Galgano MT,Hampton GM,Frierson HF.Comprehensive analysis of HE4 expression in normal and malignant human tissues[J].Mod Pathol,2006,19(6):847-853.
[5]Wang Y,Li PZ,Huang WC,et al.The diagnostic value of serum HE4,NSE,CYFRA21-1 levels of lung cancer[J].Journal of Clinical Pulmonary Medicine,2016,21(12):2159-2161.[王英,李佩章,黄文成,等.血清HE4、NSE、CYFRA21-1水平变化对肺癌的诊断价值[J].临床肺科杂志,2016,21(12):2159-2161.]
[6]Fitzmaurice C,Dicker D,Pain A,et al.The global burden of cancer2013[J].JAMA Oncology,2015,1(4):505-527.
[7]Xu LF,Hu K.Value of the CEA,SCCA,CYFRA21-1,NSE and D-D combined detection in the diagnosis of lung cancer[J].Journal of Clinical Pulmonary Medicine,2017,22(2):233-235.[许利芳,胡克.血清CEA、SCCA、CYFRA21-1、NSE与血浆D-D联合检测对肺癌诊断的临床意义[J].临床肺科杂志,2017,22(2):233-235.]
[8]Kirchhoff C,Habben I,Ivell R,et al.A major human epididymisspecific c DNA encodesa protein with sequence homology to extracellular proteinase inhibitors[J].Biol Reprod,1991,45(2):350-357.
[9]Karolina P,Bjorg KJ,Karin S,et al.Evaluation of ovarian cancer biomarkers HE4 and CA-125 women presenting with a suspicious cystic ovarian mass[J].Gynecol Oncol,2012,22(4):244-252.
[10]Braicu EI,Chekerov R,Richter R,et al.HE4 expression in plasma correlates with surgical outcome and overall survival in patients with first ovarian cancer relapse[J].Ann Surg Oncol,2014,21(3):955-962.
[11]Lamy P,Plassot C,Pujol J.Serum HE4:An independent prognos-tic factor in non-small cell lung cancer[J].PLo S One,2015,10(6):e0128836.
[12]Kong HX,Li HJ,Xu JY,et al.The clinical significance of serum MMP-9,HE4,CYFRA21-1,CEA,NSE level in lung cancer patients[J].Shandong Medical Journal,2017,57(32):73-75.[孔海霞,李洪娟,徐婧玥,等.肺癌患者血清MMP-9、HE4、CYFRA21-1、CEA、NSE水平变化及其临床意义[J].山东医药,2017,57(32):73-75.]
[13]Tang YX,Luo CH,Wang Y,et al.Expression of human epididymis protein 4 in cancer and its clinical progress[J].Anti-tumor Pharmacy,2015,5(2):87-91.[唐雨曦,罗晨辉,王瑛,等.人附睾蛋白4(HE4)在恶性肿瘤中的表达与临床进展[J].肿瘤药学,2015,5(2):87-91.]
[14]Liu LH,Luo JX,Xu YJ,et al.Comparison of serue CYFRA21-1,NSE and CEA,levels in patients with different patholgical types of lung cancer[J].Medical ournal of Wuhan University,2015,36(4):533-540.[刘连红,罗建祥,徐月君,等.不同病理类型肺癌患者血清肿瘤标志物CYFRA21-1、NSE和CEA水平的比较[J].武汉大学学报(医学版),2015,36(4):533-540.]
[15]Sun ZM.To evaluate the value of CYFRA21-1,CEA and NSE in the diagnosis of lung cancer[J].China Continuing Medical Education,2017,9(3):52-53.[孙种梅.CYFRA21-1、CEA、NSE在肺癌诊断中的价值[J].中国继续医学教育,2017,9(3):52-53.]
[16]Iwahori K,Suzuki H,Kishi Y,et al.Serum HE4 as a diagnostic and prognostic marker fo lung cancer[J].Tumour Biol,2012,33(4):1141-1149.
[17]Wang X,Fan Y,Wang J,et al.Evaluating the expression and diagnostia value of human epididymis protein 4(HE4)in small cell lung cancer[J].Tumour Biol,2014,35(7):6847-6853.