Research Article | | Peer-Reviewed

Effectiveness Analysis of the Combined Detection of CEA, SCC, CYFRA21-1, NSE and ProGRP for Early Diagnosis of Lung Cancer

Received: 25 April 2024     Accepted: 4 June 2024     Published: 19 June 2024
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Abstract

Objective To explore the diagnostic value and application effect of the combined detection of CEA (carcinoembryonic antigen), SCC (squamous cell carcinoma antigen), CYFRA21-1 (soluble fragment of cytokeratin 19), NSE (neuron specific enolase) and proGRP (gastrin releasing peptide precursor) in early lung cancer. Method 66 patients who admitted to the hospital from April 2019 to February 2024 were selected as the early stage lung cancer group and the other 159 patients were selected as the benign lung group, in which all subjects were tested for NSE, CEA, ProGRP, CYFRA21-1, and SCC levels and were confirmed by histopathological analysis. In ROC analysis, the cut-off point, AUC, accuracy, sensitivity and specificity between single and combined detection indicators are analyzed. Result The size of cut-off point, AUC, accuracy, sensitivity, specificity, positive and negative detection rate and accuracy rate is 0.3072, 0.790, 89.33%, 0.894, 0.893, 89.40% (59/66), 89.31% (142/159) and 89.33% ((142+59)/225) respectively and it is obviously superior to those of single detection method. Meanwhile, indicator of SCC showed the worst performance by single detection. Conclusion The combined detection indicators have high diagnostic value in early diagnosis of lung cancer, and the sensitivity, positive detection rate, AUC value and accuracy have been significantly improved.

Published in Science Discovery (Volume 12, Issue 3)
DOI 10.11648/j.sd.20241203.14
Page(s) 58-62
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Combined Detection, Early Lung Cancer, Tumor Markers, Effectiveness Analysis

1.引言
据报道[1],肺癌在恶性肿瘤中的发病率和死亡率是最高的,是导致癌症死亡的主要原因,幸存率较低,其中五年幸存率仅为19.4%,给人类的生命健康带来了严重挑战[2],而对于确诊为早期肺癌的患者来说,五年总体存活率大约是80%[3],得到了极大提高。为了解决全球共同关注的早期及时发现和诊断肺癌的问题,常规的血清肿瘤标志物检测因其简便快速的特点,被广泛用于肺癌的筛查和诊断。这种检查方法不仅为患者的进一步检查和治疗提供了指导,而且有助于实现早期发现和早期高效经济治疗[4]。在2019年中华医学会肺癌临床诊疗指南中,已明确将proGRP、NSE、CEA、SCC、CYFRA21-1以及NSE指标推荐为常用的肺癌标志物,检测已经被用于不同类型的肺癌检测。由于目前的单项肿瘤标志物在诊断时的敏感性和特异性尚未能满足临床的需求,因此临床上更倾向于采用多种肿瘤标志物进行联合检测[5-9],以提升肺癌诊断的敏感性和特异性。因此,本研究选择了指南推荐的5种肿瘤标志物,并分别检测了肺癌患者和肺良性疾病患者血清中这些肿瘤标志物的表达水平。同时,我们对这5种肿瘤标志物单独及联合检测在肺癌鉴别诊断中的价值进行了分析。
2.资料与方法
2.1.研究对象
获取2019年4月至2024年2月到遵义医科大学第二附属医院就诊的66例患者为早期肺癌组,同时获取159例肺部良性病变患者作为肺部非肺癌组(参照2019版,中华医学会肺癌临床诊疗指南,经过病理组织学分析确认上述两组分类)为研究对象,其中男性126例,女性99例,年龄区间为33~81岁,中位数年龄61岁,且两组之间在性别、年龄上无显著差异(P>0.05)。根据排除标准,以下几类患者将被排除:(1)病历资料不完整者;(2)缺乏明确的病理组织学或细胞学诊断,或者存在其他系统肿瘤、有其他系统肿瘤史或有其他系统肿瘤转移所致的肺癌患者;(3)肝、肾功能严重异常或患有血液系统疾病的患者。
2.2.仪器与试剂
所在检验科室的主要仪器设备有罗氏602 、全自动生化分析仪AU5800 、全自动模块式血液分析仪XN-20以及全自动凝血分析仪CS5100等,用于获取早期肺癌患者的临床检验的血清肿瘤标志物proGRP、NSE、CEA、SCC、CYFRA21-1以及NSE的水平,是开展本研究的基础。
2.3.血清肿瘤指标采集
患者均在未进行治疗和干预前,需要在入院后的第二天清晨进行空腹采血,使用促凝真空采集管采集静脉血5 mL,离心力1566×g ,转速3000rpm,离心10 min,分离血清。所有血清指标均严格按照检测试剂盒以及电化学发光全自动免疫分析仪说明书检测,各个指标的正常参考区间如下:NSE 水平(0~20mg/ml)、CYFRA21-1 水平 (0~3.3 ng/ml)、CEA 水平(0~ 5.00 ng /ml)、SCC 水平(0~25 ng /mL)、ProGRP 水平(28.3~65.7 pg/mL)。
2.4.仪器与试剂
使用统计学软件SPSS 26.0对单项检测指标以及联合检测指标进行数据分析。在分析各指标数据之前,首先进行正态性和方差齐性分析,发现计量资料对应的正态性分布不显著,因此以中位数(四分位数)来表示这些指标 ,早期肺癌组用1表示,非肺癌组用0表示,考虑到对数据的研究是2分类问题,采用二元Logistic 回归获取组合检测指标,组间比较采用 Mann-Whitney U 检验,通过ROC曲线分析,我们可以研究5种肿瘤标志物作为单独及联合检测指标对早期肺癌组与非肺癌疾病组的敏感度、截断点、阳性/阴性检出率以及准确性AUC的诊断价值进行分析,以 P<0.05为差异具有统计学意义。
3.结果
3.1.血清肿瘤标志物在组1和组0上的正态性检验
首先对5项血清肿瘤指标做正态性检验,其中早期肺癌组用1表示,非肺癌组用0表示。对获取的患者样本数据经SPSS26.0统计软件分析(见表1所示),考虑到样本量较小(小于2000),或自由度小于规定的阈值,所以采用Shapiro_wilk检验可知血清肿瘤标志物CEA、SCC、CYFRA21-1以及NSE的显著性统计P值均小于0.05,表明检验结果的正态性不显著,而proGRP指标仅在分组为0的情况下P值为0.101大于0.05,符合正态分布,因此早期肺癌组与非肺癌组的差异分析采用非参数检验方法,即采用中位数(上四分位数和下四分位数)来表示每个血清肿瘤标志物的取值范围。采用中位数对2 组(肺癌组和非肺癌组)的CEA、SCC、CYFRA21-1、NSE以及proGRP情况水平对比如表2所示,与非肺癌组相比较,早期肺癌组指标CEA、CYFRA21-1以及NSE的平均水平均高于非肺癌组,且差异有统计学意义(P<0.5),而指标proGRP与SCC水平在两组之间差异不是很显著,差异无统计学意义(P=0.0199>0.05 (ProGRP), P=0.632>0.05 (SCC))。因此,表2反映了在P值小于0.05有统计学意义情况下,说明这三个血清指标CEA、NSE、CYFRA21_1对是否存在早期肺癌的诊断具有显著价值。
表1 血清肿瘤标志物的Shapiro_wilk正态检验。

检测指标

分组

统计

自由度

显著性

SCC

0

0.210

159

.000

1

0.618

66

.000

proGRP

0

0.955

159

.101

1

0.287

66

.000

CEA

0

0.638

159

.000

1

0.285

66

.000

NSE

0

0.694

159

.000

1

0.606

66

.000

CYFRA21_1

0

0.464

159

.000

1

0.426

66

.000

Table 表2 两组患者的5种血清肿瘤标志物检测结果比较[. M(P25, P75)]。

指标

分组1:n = 99

分组0:n = 126

ProGRP (pg/mL)

33.75 (27.73, 45.15)

0.199

32.60 (23.55, 41.25)

0.199

NSE (ng/ml)

17.37 (13.08, 27.55)

0.021

13.54 (11.69, 19.95)

0.021

CEA (ng/ml)

2.45 (1.47, 5.53)

0.002

1.51 (1.10, 2.40)

0.002

CYFRA21-1 (ng/ml)

3.81 (2.50, 6.23)

0.000

2.24 (1.60, 2.90)

0.000

SCC (ng/mL)

0.80 (0.50, 1.00)

0.632

0.70 (0.55, 0.95)

0.632

3.2.获取5项血清肿瘤指标的联合指标检
患者接下来,通过5项指标联合检测分析ROC曲线对早期肺癌的诊断效能,是否优于传统的单项指标检测。首先,运用分类算法的二元Logistics回归获取5项血清肿瘤指标的联合指标,将用于ROC曲线的敏感度、特异性、截断点(cut-off)、约登指数以及ROC曲线下方面积的计算,其中在计算各单项指标以及联合指标的最佳截断值时,采用的最大约登指数对应的指标值。
3.3.单项及联合检测的ROC曲线对早期肺癌的诊断效能分析
通过ROC曲线对单项以及联合指标检测对早期肺癌的诊断效能分析如表3所示,在单项检测中发现,单项血清指标中proGRP、NSE、CEA、CYFRA21-1、SCC的敏感度分别为0.091、0.621、0.303、0.773、0.091,其中在统计学有意义条件下(P<0.05)CYFRA21-1在单项指标检测中的敏感度最高为0.773,proGRP中的敏感度最低,为0.091,特异度达到了1,但从敏感度和特异度的平衡来看,CYFRA21-1的检测效果更好,而采用5项指标联合检测时所对应的敏感度为0.894,在所有单指标检测中表现最好,特异度为0.893,低于CEA、SCC以及proGRP指标,但差异有统计学意义(P<0.05),而且数据间比较有统计学意义(P<0.05),综合平衡效果最好。单项血清指标CEA、SCC、CYFRA21-1、NSE、proGRP在ROC曲线下方的面积(AUC)分别为0.685(95%CI:0.582~0.789)、0.528(95%CI:0.413~0.643)、0.775(95%CI:0.683~0.867)、0.636(95%CI:0.526~0.747)、0.576(95%CI:0.460~0.692),5种联合指标识别早期肺癌的AUC为0.829(95%CI:0.701~0.879)。从AUC值来看,联合检测 > CYFRA21-1 > CEA > NSE > proGRP > SCC ,说明联合指标检测的AUC最高,准确性为89.33% (201/225),阳性预测值为89.39% (59/66),阴性预测值为89.33% (142/159),这几项评估标准也是所有单项指标检测中最高,进一步验证联合指标检测在早期肺癌的诊断中具有较高的准确性。
表3 单项指标与联合指标检测的诊断效能。

指标

proGRP

NSE

CEA

CYFRA21-1

SCC

联合检测

截断值

98.200

15.1350

4.4000

2.41000

2.950

0.3072050

敏感度

0.091

0.621

0.303

0.773

0.091

0.894

特异度

1.000

0.610

0.943

0.522

0.943

0.893

约登指数

0.090909

0.231275

0.246427

0.29474

0.034305

0.787021

AUC值

0.576

0.636

0.685

0.775

0.528

0.829

P值

0.199>0.05

0.021<0.05

0.002<0.05

0.000<0.05

0.632>0.05

0.000<0.05

阳性预测值

9.01% (6/66)

62.12% (41/66)

30.3% (20/66)

77.27% (51/66)

9.01% (6/66)

89.39% (59/66)

阴性预测值

100% (159/159)

61.01% (97/159)

94.34% (150/159)

52.20% (83/159)

94.34% (150/159)

89.31% (142/159)

准确性

73.33% (165/225)

61.33% (138/225)

75.56% (170/225)

59.56% (134/225)

69.33% (156/225)

89.33% (201/225)

为了进一步论证联合指标检测相比于单项指标检测的优越性,图1给出了不同检测指标的ROC曲线,AUC表示ROC曲线下方区域的面积,该值越大越好,对上述指标的AUC值进行统计学检验发现,联合检测、CEA、NSE以及CYFRA21_1指标的P小于0.05,认为对应的AUC值存在显著统计学差异。一般情况下,当AUC值在0.7到0.9之间时,代表这种指标可以较好的用于预测结果,若大于0.9则表示预测结果非常好。显然,从图1可知,联合检测具有更大的AUC值,达到了0.829,其次是CYFRA21_1指标,AUC值为0.775,关于单指标检测及联合检测在ROC曲线中的更多相关参数反映如表3所示,无论采用何种检测,AUC值均大于0.5,但SCC仅为0.528,proGRP为0.576,对应的P值分别为0.632和0.199,均大于0.05,表明该值不存在显著性差异。由于肺部具有丰富的血管网络,这使得癌细胞在早期就发生转移提供了更多的可能性。同时,早期肺癌患者通常没有显著的临床症状,当症状出现时,疾病往往已经发展到晚期,从而增加了治疗的难度[10-15]。在这种情况下,组织活检被公认为是检测肺癌的黄金标准,但这种方法的操作是有创性的,部分患者可能不愿意接受。因此,早期诊断肺癌是广大医护工作者的首要目标之一。在这个背景下,血清肿瘤标志物对肺癌的诊断具有一定的价值,但单一的血清肿瘤标志物诊断缺乏一定的特异性和敏感性[16-18]。为了提高诊断的准确性和效率,临床上更倾向于采用多种肿瘤标志物进行联合检测。
图1 各个指标ProGRP、NSE、CEA、CYFRA21-1、SCC单独检测及其联合检测对早期肺癌诊断的ROC曲线。
4.结论
本研究结果表明,联合指标检测方法在早期肺癌诊断中具有显著优势。首先,联合检测方法提高了灵敏度,能够更有效地识别出早期肺癌患者。其次,联合检测方法的AUC值最高,说明其准确性较高。此外,联合检测方法的阳性预测值和整体准确性均优于单指标检测,降低了漏诊率和误诊率,进一步表明联合检测方法能够更准确地诊断早期肺癌。
综上所述,联合检测CEA、CYFRA21-1和NSE对于诊断早期肺癌具有更高的价值。这种联合检测方法可以显著提高早期肺癌诊断的灵敏度和特异度,为肺癌的早期发现和预后治疗提供重要的参考价值。通过这种联合检测方法,我们可以在早期发现肺癌,并及早采取有效的治疗措施,从而提高患者的生存率和治愈率。
致谢
本文为贵州省教育厅青年科技人才成长项目《基于血清多参数的机器学习方法建立肺癌早期诊断模型及临床应用研究》(黔教合KY字[2022]285号)的阶段性成果之一。
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    Zhou, S., Ge, X., Yang, Z., Zeng, F. (2024). Effectiveness Analysis of the Combined Detection of CEA, SCC, CYFRA21-1, NSE and ProGRP for Early Diagnosis of Lung Cancer. Science Discovery, 12(3), 58-62. https://doi.org/10.11648/j.sd.20241203.14

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    ACS Style

    Zhou, S.; Ge, X.; Yang, Z.; Zeng, F. Effectiveness Analysis of the Combined Detection of CEA, SCC, CYFRA21-1, NSE and ProGRP for Early Diagnosis of Lung Cancer. Sci. Discov. 2024, 12(3), 58-62. doi: 10.11648/j.sd.20241203.14

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    AMA Style

    Zhou S, Ge X, Yang Z, Zeng F. Effectiveness Analysis of the Combined Detection of CEA, SCC, CYFRA21-1, NSE and ProGRP for Early Diagnosis of Lung Cancer. Sci Discov. 2024;12(3):58-62. doi: 10.11648/j.sd.20241203.14

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  • @article{10.11648/j.sd.20241203.14,
      author = {Shufang Zhou and Xiaojun Ge and Zhifang Yang and Fei Zeng},
      title = {Effectiveness Analysis of the Combined Detection of CEA, SCC, CYFRA21-1, NSE and ProGRP for Early Diagnosis of Lung Cancer
    },
      journal = {Science Discovery},
      volume = {12},
      number = {3},
      pages = {58-62},
      doi = {10.11648/j.sd.20241203.14},
      url = {https://doi.org/10.11648/j.sd.20241203.14},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.sd.20241203.14},
      abstract = {Objective To explore the diagnostic value and application effect of the combined detection of CEA (carcinoembryonic antigen), SCC (squamous cell carcinoma antigen), CYFRA21-1 (soluble fragment of cytokeratin 19), NSE (neuron specific enolase) and proGRP (gastrin releasing peptide precursor) in early lung cancer. Method 66 patients who admitted to the hospital from April 2019 to February 2024 were selected as the early stage lung cancer group and the other 159 patients were selected as the benign lung group, in which all subjects were tested for NSE, CEA, ProGRP, CYFRA21-1, and SCC levels and were confirmed by histopathological analysis. In ROC analysis, the cut-off point, AUC, accuracy, sensitivity and specificity between single and combined detection indicators are analyzed. Result The size of cut-off point, AUC, accuracy, sensitivity, specificity, positive and negative detection rate and accuracy rate is 0.3072, 0.790, 89.33%, 0.894, 0.893, 89.40% (59/66), 89.31% (142/159) and 89.33% ((142+59)/225) respectively and it is obviously superior to those of single detection method. Meanwhile, indicator of SCC showed the worst performance by single detection. Conclusion The combined detection indicators have high diagnostic value in early diagnosis of lung cancer, and the sensitivity, positive detection rate, AUC value and accuracy have been significantly improved.
    },
     year = {2024}
    }
    

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  • TY  - JOUR
    T1  - Effectiveness Analysis of the Combined Detection of CEA, SCC, CYFRA21-1, NSE and ProGRP for Early Diagnosis of Lung Cancer
    
    AU  - Shufang Zhou
    AU  - Xiaojun Ge
    AU  - Zhifang Yang
    AU  - Fei Zeng
    Y1  - 2024/06/19
    PY  - 2024
    N1  - https://doi.org/10.11648/j.sd.20241203.14
    DO  - 10.11648/j.sd.20241203.14
    T2  - Science Discovery
    JF  - Science Discovery
    JO  - Science Discovery
    SP  - 58
    EP  - 62
    PB  - Science Publishing Group
    SN  - 2331-0650
    UR  - https://doi.org/10.11648/j.sd.20241203.14
    AB  - Objective To explore the diagnostic value and application effect of the combined detection of CEA (carcinoembryonic antigen), SCC (squamous cell carcinoma antigen), CYFRA21-1 (soluble fragment of cytokeratin 19), NSE (neuron specific enolase) and proGRP (gastrin releasing peptide precursor) in early lung cancer. Method 66 patients who admitted to the hospital from April 2019 to February 2024 were selected as the early stage lung cancer group and the other 159 patients were selected as the benign lung group, in which all subjects were tested for NSE, CEA, ProGRP, CYFRA21-1, and SCC levels and were confirmed by histopathological analysis. In ROC analysis, the cut-off point, AUC, accuracy, sensitivity and specificity between single and combined detection indicators are analyzed. Result The size of cut-off point, AUC, accuracy, sensitivity, specificity, positive and negative detection rate and accuracy rate is 0.3072, 0.790, 89.33%, 0.894, 0.893, 89.40% (59/66), 89.31% (142/159) and 89.33% ((142+59)/225) respectively and it is obviously superior to those of single detection method. Meanwhile, indicator of SCC showed the worst performance by single detection. Conclusion The combined detection indicators have high diagnostic value in early diagnosis of lung cancer, and the sensitivity, positive detection rate, AUC value and accuracy have been significantly improved.
    
    VL  - 12
    IS  - 3
    ER  - 

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Author Information
  • Department of Laboratory Medicine, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, China; School of Laboratory Medicine, Zunyi Medical University, Zunyi, China

  • Department of Laboratory Medicine, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, China; School of Laboratory Medicine, Zunyi Medical University, Zunyi, China

  • Department of Laboratory Medicine, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, China; School of Laboratory Medicine, Zunyi Medical University, Zunyi, China

  • Department of Laboratory Medicine, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, China; School of Laboratory Medicine, Zunyi Medical University, Zunyi, China