Diagnostic Value of Serum Pro-gastrin-releasing Peptide and Neuron-specific Enolase for Small Cell Lung Cancer and Its Influencing Factors
-
摘要:
目的 分析评价血清胃泌素释放肽前体(pro-gastrin-releasing peptide, ProGRP)和神经元烯醇化酶(neuron-specific enolase, NSE)在小细胞肺癌(small cell lung cancer, SCLC)患者临床辅助诊断中的作用及干扰因素。 方法 2010年7月至2012年6月在北京协和医院住院的SCLC患者(SCLC组)93例、非小细胞肺癌(non-small cell lung cancer, NSCLC)患者(NSCLC组)120例、肺良性疾病患者(肺良性疾病组)120例及健康者(健康对照组)90名, 分别采用ELISA法测定各组血清ProGRP和NSE浓度; 化学发光免疫分析和电化学发光免疫分析方法评价标本溶血和患者肾功能损害对2项指标在SCLC诊断中的影响。 结果 SCLC组的血清ProGRP和NSE浓度分别为90.61(11.75~20 020.90)ng/L和13.18(3.05~201.88)μg/L; NSCLC组为13.26(8.54~526.23)ng/L和5.86(1.80~100.90)μg/L; 肺良性疾病组为24.65(1.32~802.93)ng/L和7.22(1.36~174.62)μg/L; 健康对照组为14.74(4.59~100.86)ng/L和4.95(1.31~10.58)μg/L; SCLC组与其他组相比差异均具有统计学意义(P < 0.01)。血清ProGRP诊断SCLC的受试者工作特征曲线下面积为0.856±0.023(95% CI:0.811~0.901);以46 ng/L为临界值时, 其敏感度、特异度、阳性预测值、阴性预测值和约登指数分别为64.5%(60/93)、94.2%(311/330)、75.9%(60/79)、90.4%(311/344)和58.7%。标本溶血严重影响NSE的检测水平, 导致NSE结果升高; 患者肾功能损害则使ProGRP的检测结果升高。 结论 血清ProGRP和NSE均为辅助诊断SCLC较好的指标, ProGRP与NSE组合的临床诊断价值较高。标本溶血严重导致NSE的检测结果升高, 患者肾功能损害则使ProGRP的检测结果升高。 Abstract:Objective To investigate the clinical significance and influencing factors of serum levels of pro-gastrin-releasing peptide (ProGRP) and neuron-specific enolase (NSE) in the diagnosis of small cell lung cancer (SCLC). Methods The levels of serum ProGRP and NSE in 93 SCLC patients (SCLC group), 120 non-small cell lung cancer (NSCLC) patients (NSCLC group), 120 benign pulmonary disease patients (benign disease group), and 90 healthy people (healthy control group) were determined using enzyme-linked immunosorbent assay (ELISA). The potential impacts of the hemolysis in samples and impaired renal function on ProGRP and NSE were tested via electroluminescent and chemiluminescent immunoassay, respectively. Results The serum ProGRP and NSE concentrations were 90.61(11.75-20 020.90)ng/L and 13.18(3.05-201.88)μg/L, respectively, in SCLC group; 13.26(8.54-526.23)ng/L and 5.86(1.80-100.90)μg/L in NSCLC group; 24.65(1.32-802.93)ng/L and 7.22(1.36-174.62)μg/L in benign disease group; and 14.74(4.59-100.86)ng/L and 4.95(1.31-10.58)μg/L in healthy control group. The levels in the SCLC group were significantly different from those in the other three groups (all P < 0.01).The area under the receiver operating characteristic curve of ProGRP was (0.856±0.023) (95% CI: 0.811-0.901). When the cutoff value of ProGRP was set at 46 ng/L, the diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and Youden's index were 64.5%(60/93), 94.2% (311/330), 75.9% (60/79), 90.4% (311/344), and 58.7%, respectively, showing good detection performance. Sample hemolysis seriously improved the detection results of NSE. Patients with impaired renal function had higher ProGRP levels. Conclusions The serum ProGRP and NSE levels are valuable tumor markers for the diagnosis of SCLC. Detection of both markers are particularly useful for the monitoring of SCLC.Sample hemolysis may seriously increase the detected NSE level, whereas impaired renal function may increase the detected ProGRP level. -
图 1 标本溶血对ProGRP和NSE测定的影响
A.稀释的溶血标本对ProGRP和NSE浓度的影响;B.患者标本溶血程度和NSE浓度的关系;C.患者标本溶血程度和ProGRP浓度的关系
ProGRP、NSE:同表 1图 2 肾功能损害患者血清Cr水平与ProGRP(A)和NSE(B)浓度的关系
ProGRP、NSE:同表 1; Cr:肌酐
表 1 各组患者血清ProGRP和NSE浓度比较[M(Q1~Q3)]
组别 ProGRP(ng/L) NSE(μg/L) 健康对照组
(n=90)14.74(4.59~100.86) 4.95(1.31~10.58) 肺良性疾病组
(n=120)24.65(1.32~802.93) 7.22(1.36~174.62) NSCLC
(n=120)13.26(8.54~526.23 5.86(1.80~100.90) SCLC
(n=93)90.61*(11.75~20 020.90) 13.18*(3.05~201.88) ProGRP:胃泌素释放肽前体;NSE:神经元烯醇化酶;SCLC:小细胞肺癌;NSCLC:非小细胞肺癌;与健康对照组、肺良性疾病组和NSCLC组比较, *P<0.01 -
[1] Govindan R, Page N, Morgensztern D, et al.Changing epidemiology of small-cell lung cancer in the United States over the last 30 years:analysis of the surveillance, epidemiologic, and end results database[J].J Clin Oncol, 2006, 24:4539-4544. doi: 10.1200/JCO.2005.04.4859 [2] Ulahannan SV, Brahmer JR.Antiangiogenic agents in combination with chemotherapy in patients with advanced non-small cell lung cancer[J].Cancer Invest, 2011, 29:325-337. doi: 10.3109/07357907.2011.554476 [3] Molina R, Auge JM, Filella X, et al.Pro-gastrin releasing peptide (ProGRP) in patients with benign and malignant diseases:comparison with CEA, SCC, CYFRA 21-1 and NSE in patients with lung cancer[J].Anticancer Res, 2005, 25(3A):1773-1778. http://europepmc.org/abstract/MED/16033098 [4] Emin Erbaycu A, Gunduz A, Batum O, et al. Pretreatment and treatment induced neuron-specific enolase in patients with small cell lung cancer:an open prospective study[J].Arch Bronconeumol, 2010, 46:364-369. [5] Molina R, Au JM, Bosch X, et al.Usefulness of serum tumor markers, including progastrin-releasing peptide, in patients with lung cancer:correlation with histology[J].Tumour Bid, 2009, 30:121-129. doi: 10.1159/000224628 [6] Hurwitz JL, Mccoy F, Scullin P, et al.New advances in the secand-line treatment of small cell lung cancer[J].Oncologist, 2009, 14:986-994. doi: 10.1634/theoncologist.2009-0026 [7] Harmsma M, Schutte B, Ramaekers FC. Serum markers in small cell lung cancer:opportunities for improvement[J]. Biochim Biophys Acta, 2013, 1836:255-272. http://europepmc.org/abstract/med/23796706 [8] Tang H, Zhang XL, Zhang ZH, et al. Diagnostic value of tumor marker pro-gastrin-releasing peptide in patients with small cell lung cancer:a systematic review[J]. Chin Med J, 2011, 124:1563-1568. http://www.cqvip.com/QK/85656X/201110/38113239.html [9] Molina R, Filella X, Aust JM.ProGRP:a new biomarker for small cell lung cancer[J].Clin Biochem, 2004, 37:505-511. doi: 10.1016/j.clinbiochem.2004.05.007 [10] Wojcik E, Rychlik U, Skotnicki P, et al. Utility of ProGRP determinations in cancer patients[J]. Clin Lab, 2010, 56:527-534. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=110da26372b93c636ab4afcff6fe51e1 [11] 薛峰, 王莉彦, 张明岩, 等.小细胞肺癌患者治疗前后血清NSE测定的临床意义[J].中国肺癌杂志, 2011, 14:723-726. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=zgfazz201109006 [12] Kim HR, Oh IJ, Shin MG, et al. Plasma proGRP concentration is sensitive and specific for discriminating small cell lung cancer from nonmalignant conditions or non-small cell lung cancer[J]. J Korean Med Sci, 2011, 26:625-630. doi: 10.3346/jkms.2011.26.5.625 [13] 盛雅娟, 刘卫国, 曹文明, 等.乳腺癌复发/转移部位及生存与血清癌抗原15-3、碱性磷酸酶水平的关系[J].中华实验外科杂志, 2012, 29:2291-2294. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=zhsywk201211068