[Establishment of cut-off value of serum pro-gastrin-releasing peptide for diagnosis of small cell lung cancer and evaluation on the clinical diagnosis efficiency]

Zhonghua Yi Xue Za Zhi. 2017 Sep 12;97(34):2657-2662. doi: 10.3760/cma.j.issn.0376-2491.2017.34.004.
[Article in Chinese]

Abstract

Objective: To determine critical reference value (cut-off value) of serum pro-gastrin-releasing peptide (ProGRP) and neuron specific enolase(NSE) in the diagnosis of small cell lung cancer(SCLC). To evaluate the clinical significance of serum levels of ProGRP and NSE in diagnosis and differential diagnosis in SCLC. Methods: Three hundred and fifty-two SCLC patients, 163 non small cell lung cancer(NSCLC)patients , 193 benign pulmonary disease patients and 140 healthy people visiting in National Cancer Hospital were analyzed retrospectively from January 2014 to July 2017.The levels of serum ProGRP and NSE of people were determined using electrochemiluminescent immunoassay respectively . Reference value ranges of the makers were determined by using the method of ROC curves. Results: In NSCLC group, benign lung disease group, healthy control group and mixed group (NSCLC+ lung benign diseases+ healthy control group) as a reference, the cut-off values were 58.3, 62.3, 57.8, 61.3 ng/L. In the diagnosis and differential diagnosis of SCLC and NSCLC, benign lung diseases, healthy controls and mixed group, AUC of ProGRP was 0.940 (0.919-0.961), 0.941 (0.921-0.960), 0.959 (0.944-0.975), 0.946 (0.928-0.963) respectively. The sensitivities of ProGRP were 86.4%, 84.9%, 86.4% and 84.7% respectively. The specificities of ProGRP were 95.7%, 96.9%, 99.3%, 98% respectively. In all groups the Youden's index of ProGRP and NSE were 0.821 vs 0.612, 0.818 vs 0.674, 0.857 vs 0.810, 0.827 vs 0.674. In healthy controls, no statistically significant difference was found between ProGRP and NSE (P>0.05) in the diagnosis of AUC. However, in the remaining 3 groups, the ProGRP diagnosis of AUC was significantly greater than that of NSE (P<0.01). Compared with single marker detection, the sensitivity of combined detection of ProGRP and NSE in diagnosis of SCLC increased to 95.5%, 94%, 96.6% and 94% in each group. There was no significant difference between ProGRP and ProGRP+ NSE in the diagnosis of AUC when compared with the NSCLC group and the mixed group (P>0.05). However, when combined with a healthy control group and a benign lung disease group, the ProGRP+ NSE combination was the highest for AUC diagnosis, compared with ProGRP and NSE (P<0.01). In the SCLC ED group serum ProGRP and NSE levels[776.33(3 103.4)ng/L, 52.14(60.59)μg/L]were higher than those in the SCLC LD group[295.59(799.65)ng/L, 23.36(22.97)μg/L], respectively (all P<0.001). The serum ProGRP levels of N0, N1, N2 and N3 in TNM staging were 113.0(343.65), 167.04(724.56), 427.42(1 388.62), 735.99(1 709.95)ng/L respectively (all P<0.001). Serum ProGRP and NSE levels were not statistically different between the sex groups and the age groups (all P>0.05). Conclusion: To establish the cut-off value of serum ProGRP is helpful for the diagnosis and differential diagnosis of SCLC.

目的: 建立血清胃泌素释放肽前体(ProGRP)和神经元特异性烯醇化酶(NSE)在诊断小细胞肺癌(SCLC)的临界参考值(cut-off值),评价血清ProGRP和NSE水平在SCLC诊断及鉴别诊断中的临床价值。 方法: 回顾性分析2014年1月至2016年7月中国医学科学院肿瘤医院就诊的352例SCLC患者、163例非小细胞肺癌(NSCLC)患者、193例肺部良性疾病患者和140名表观健康对照者,采用电化学发光方法测定其血清ProGRP和NSE浓度。应用ROC曲线法确定血清ProGRP和NSE的cut-off值,评估其临床诊断价值。 结果: 分别以NSCLC组、肺良性疾病组、健康对照组、混合组(NSCLC+肺良性疾病+健康对照组)为参照,其cut-off值分别为58.3、62.3、57.8、61.3 ng/L时,ProGRP在诊断和鉴别诊断SCLC和NSCLC、肺良性疾病、健康对照者、混合组的曲线下面积(AUC)分别为0.940(0.919~0.961)、0.941(0.921~0.960)、0.959(0.944~0.975)、0.946(0.928~0.963),此时,敏感度分别为86.4%、84.9%、86.4%、84.7%,特异度分别为95.7%、96.9%、99.3%、98.0%。各组别中的ProGRP和NSE的约登指数分别为0.821比0.612、0.818比0.674、0.857比0.810、0.827比0.674。在健康对照组中ProGRP与NSE诊断AUC差异无统计学意义(P>0.05);而在其余3组中ProGRP诊断AUC明显大于NSE(P<0.01)。与单项指标检测相比,各组中ProGRP和NSE联合检测诊断SCLC时的敏感度提高至95.5%、94.0%、96.6%、94.0%。在与NSCLC组和混合组做鉴别诊断时,ProGRP与ProGRP+NSE联合诊断的AUC差异无统计学意义(P>0.05)。但在与健康对照组和肺良性疾病组做鉴别诊断时,ProGRP+NSE联合诊断AUC最高,明显高于ProGRP和NSE(P<0.01)。SCLC广泛期(ED)组治疗前血清ProGRP和NSE水平[776.33(3 103.4)ng/L,52.14(60.59)μg/L]均高于SCLC局限期(LD)组[295.59(799.65)ng/L,23.36(22.97)μg/L],(均P<0.001)。TNM分期中的N0、N1、N2、N3的血清ProGRP分别为113.0(343.65)、167.04(724.56)、427.42(1 388.62)、735.99(1 709.95)ng/L,差异有统计学意义(P<0.001)。血清ProGRP和NSE水平在不同性别组和年龄组中差异无统计学意义(均P>0.05)。 结论: 血清ProGRP cut-off值的建立有助于诊断和鉴别诊断SCLC。.

Keywords: Diagnosis; Neuron specific enolase; Pro-gastrin-releasing peptide; Reference values; Small cell lung carcinoma.

MeSH terms

  • Biomarkers, Tumor
  • Carcinoma, Non-Small-Cell Lung
  • Gastrin-Releasing Peptide
  • Humans
  • Lung Neoplasms*
  • Peptide Fragments
  • Phosphopyruvate Hydratase
  • Recombinant Proteins
  • Retrospective Studies
  • Small Cell Lung Carcinoma*

Substances

  • Biomarkers, Tumor
  • Peptide Fragments
  • Recombinant Proteins
  • Gastrin-Releasing Peptide
  • Phosphopyruvate Hydratase