Performances of CYFRA 21-1, Carcinoembryonic Antigen and Their Combination for Lung Cancer Diagnosis

Jin Ju Kim; Hyo Jun Ahn; Yongjung Park

doi:10.3343/lmo.2020.10.1.66

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Kim, Ahn, and Park: Performances of CYFRA 21-1, Carcinoembryonic Antigen and Their Combination for Lung Cancer Diagnosis

Original Article

Laboratory Medicine Online 2020; 10(1): 66-74.

Published online: 27 December 2019

DOI: https://doi.org/10.3343/lmo.2020.10.1.66

Performances of CYFRA 21-1, Carcinoembryonic Antigen and Their Combination for Lung Cancer Diagnosis

Jin Ju Kim, M.D.¹, Hyo Jun Ahn, M.T.², Yongjung Park, M.D.²

¹Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea.

²Department of Laboratory Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Korea.

Corresponding author: Yongjung Park, M.D., Ph.D. National Health Insurance Service Ilsan Hospital, 100 Ilsan-ro, Ilsandong-gu, Goyang 10444, Korea. Tel: +82-31-900-0906, Fax: +82-31-900-0925, myiq2000@nhimc.or.kr

Received 12 February 2019 Revised 13 May 2019 Accepted 15 May 2019

Laboratory Medicine Online

(open-access):

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

Abstract

Background

The aim of this study was to compare the efficiency of cytokeratin 19 fragment (CYFRA 21-1) and carcinoembryonic antigen (CEA) for the diagnosis of lung cancer and to establish the optimal cut-off values.

Methods

We retrospectively reviewed the medical records of 1,176 subjects with CYFRA 21-2 and CEA data; they were classified into 93 lung cancer cases and 1,083 total controls, including 146 age-matched controls. Multivariate analysis was used to determine the relationship between the concentration of each tumor marker and lung cancer diagnosis. The diagnostic efficiencies of tumor markers were evaluated using receiver operating characteristic curve analysis and areas under the curve (AUCs) were calculated. The optimal cut-offs for CYFRA 21-1 and CEA were also estimated.

Results

Age, CYFRA 21-1, and CEA concentrations were independently associated with lung cancer diagnosis. Diagnostic efficiency of each tumor marker and its' combination was different according to the histological types of lung cancer. For non-small cell lung cancer, the AUCs for the two-marker combination were the highest: 0.8661 and 0.7559 for total and age-matched controls, respectively. For squamous cell carcinoma, the AUCs for CYFRA 21-1 were the highest: 0.9245 and 0.8428 for total and age-matched controls, respectively. The sensitivity and specificity of CYFRA 21-1 and CEA for lung cancer diagnosis were improved when the cutoffs determined based on this study were applied.

Conclusions

CYFRA 21-1 and CEA could be useful markers for diagnosing lung cancer and single or combination of markers may be useful according to different histological types of lung cancer.

Keywords: CYFRA 21-1, Carcinoembryonic antigen (CEA), Tumor marker, Lung cancer

Figures and Tables

Fig. 1

Receiver operating characteristic curve analysis for the discrimination of lung cancer patients (N=93) from age-matched controls (N=146). Area under the curve (AUC) values for CYFRA 21-1, CEA, and their combination were compared pairwise. (A) Non-small cell lung cancer (N=86): CYFRA 21-1 vs. CEA, P=0.5578; CYFRA 21-1 vs. CYFRA 21-1+CEA, P=0.1163; CEA vs. CYFRA 21-1+CEA, P=0.0159. (B) Adenocarcinoma (N=50): CYFRA 21-1 vs. CEA, P=0.2803; CYFRA 21-1 vs. CYFRA 21-1+CEA, P=0.0783; CEA vs. CYFRA 21-1+CEA, P=0.7705. (C) Squamous cell carcinoma (N=18): CYFRA 21-1 vs. CEA, P=0.0005; CYFRA 21-1 vs. CYFRA 21-1+CEA, P=0.1130; CEA vs. CYFRA 21-1+CEA, P=0.0027. (D) All types of lung cancers (N=93): CYFRA 21-1 vs. CEA, P=0.4990; CYFRA 21-1 vs. CYFRA 21-1+CEA, P=0.1161; CEA vs. CYFRA 21-1+CEA, P=0.0119.

Abbreviations: CI, confidence interval; FPF, false positive fraction; TPF, true positive fraction.

Table 1

Characteristics of patient population

^aData are shown as median (1st to 3rd quartiles).

^bIncludes cases of sarcomatoid carcinoma (N=3), adenosquamous carcinoma (N=1), mucoepidermoid carcinoma (N=1), and poorly differentiated carcinoma (N=1).

Table 2

CYFRA 21-1 and CEA levels in control groups

Data are shown as median (1st to 3rd quartiles).

^avs. healthy subjects.

Table 3

CYFRA 21-1 and CEA levels according to the histological classifications and stages of lung cancer

Data are shown as median (1st to 3rd quartiles).

^avs. adenocarcinoma or stage I.

^bIncludes cases of sarcomatoid carcinoma (N=3), adenosquamous carcinoma (N=1), mucoepidermoid carcinoma (N=1), and poorly differentiated carcinoma (N=1).

Table 4

Multivariate analysis using patients' age, sex, and CYFRA 21-1 and CEA levels for the discrimination of lung cancer (N=93) patients from total control subjects (N=1,083)

Abbreviation: CI, confidence interval.

Table 5

Efficiencies of CYFRA 21-1 and CEA as diagnostic markers for lung cancer

Abbreviations: CI, confidence interval; PPV, positive predictive value; NPV, negative predictive value; NSCLC, non-small cell lung cancer; SCC, squamous cell carcinoma.

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ORCID iDs: Yongjung Park
https://orcid.org/0000-0001-5668-4120
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