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ORIGINAL ARTICLE
Year : 2014  |  Volume : 10  |  Issue : 7  |  Page : 131-134

The value of serum Cyfra21-1 as a biomarker in the diagnosis of patients with non-small cell lung cancer: A meta-analysis


1 Department of Thoracic Surgery, Tianjin Haihe Hospital, Tianjin 300350, China
2 Department of Oncology, Tianjin Haihe Hospital, Tianjin 300350, China
3 Department of Thoracic Surgery, Tianjin Union Medical Center, Tianjin 300121, China

Date of Web Publication29-Nov-2014

Correspondence Address:
Jundong Gu
Department of Thoracic Surgery, Tianjin Union Medical Center, Tianjin 300121
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.145835

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 > Abstract 

Objective: The serum level of Cyfra21-1 was always elevated in patients with nonsmall cell lung carcinoma. The aim of this meta-analysis was to evaluate the serum Cyfra21-1 as a biomarker in the diagnosis of nonsmall cell lung cancer (NSCLC).
Methods: All the articles associated with serum Cyfra21-1 in the diagnosis of NSCLC were searched in the PubMed, Medline, and CNKI databases. The number of patients for true positive, false positive, false negative and true negative were extracted from each individual study. The pooled sensitivity, specificity, positive likely hood ratio (+lr), negative likely hood ratio (−lr), diagnosis odds ratio (dor) and summary receiver operating characteristic (sroc) curve were calculated by MetaDiSc 1.4 software.
Results: After searching the databases, 17 studies with 4221 subjects were met the inclusion criteria and finally included in this meta-analysis. The pooled diagnosis sensitivity, specificity, +lr, −lr and dor were 0.72 (95% confidence interval [CI]: 0.70-0.73), 0.94 (95%CI: 0.93-0.95), 8.81 (95%CI: 6.36-12.22), 0.42 (95%CI: 0.32-0.55) and 22.57 (95%CI: 13.89-36.68) respectively. The area under the sroc curve was 0.95. And significant publication bias was found in this meta-analysis (P = 0.049).
Conclusion: With published data, the serum Cyfra21-1 was a useful biomarker for diagnosis of NSCLC.Objective: The serum level of Cyfra21-1 was always elevated in patients with nonsmall cell lung carcinoma. The aim of this meta-analysis was to evaluate the serum Cyfra21-1 as a biomarker in the diagnosis of nonsmall cell lung cancer (NSCLC).
Methods: All the articles associated with serum Cyfra21-1 in the diagnosis of NSCLC were searched in the PubMed, Medline, and CNKI databases. The number of patients for true positive, false positive, false negative and true negative were extracted from each individual study. The pooled sensitivity, specificity, positive likely hood ratio (+lr), negative likely hood ratio (−lr), diagnosis odds ratio (dor) and summary receiver operating characteristic (sroc) curve were calculated by MetaDiSc 1.4 software.
Results: After searching the databases, 17 studies with 4221 subjects were met the inclusion criteria and finally included in this meta-analysis. The pooled diagnosis sensitivity, specificity, +lr, −lr and dor were 0.72 (95% confidence interval [CI]: 0.70-0.73), 0.94 (95%CI: 0.93-0.95), 8.81 (95%CI: 6.36-12.22), 0.42 (95%CI: 0.32-0.55) and 22.57 (95%CI: 13.89-36.68) respectively. The area under the sroc curve was 0.95. And significant publication bias was found in this meta-analysis (P = 0.049).
Conclusion: With published data, the serum Cyfra21-1 was a useful biomarker for diagnosis of NSCLC.

Keywords: Cyfra21-1, diagnosis, meta-analysis, nonsmall cell lung carcinoma


How to cite this article:
Cui C, Sun X, Zhang J, Han D, Gu J. The value of serum Cyfra21-1 as a biomarker in the diagnosis of patients with non-small cell lung cancer: A meta-analysis. J Can Res Ther 2014;10, Suppl S3:131-4

How to cite this URL:
Cui C, Sun X, Zhang J, Han D, Gu J. The value of serum Cyfra21-1 as a biomarker in the diagnosis of patients with non-small cell lung cancer: A meta-analysis. J Can Res Ther [serial online] 2014 [cited 2019 Aug 20];10:131-4. Available from: http://www.cancerjournal.net/text.asp?2014/10/7/131/145835

Chao Cui and Xin Sun contribute equally to this work



 > Introduction Top


Cyfra21-1 assay is a test which was developed for evaluation of cytokeratin 19 fragment in serum, especially in patients with nonsmall cell lung cancer (NSCLC). [1] Important progress in biochemical diagnostics for NSCLC with the introduction of determinations for the serum Cyfra21-1 has been made. [2] Several studies have demonstrated that the serum Cyfra21-1 was elevated in patients with NSCLC. [3],[4] Nevertheless, the diagnosis value of serum Cyfra21-1 was varied a lot. The differences may due to the structure of the analyzed group of patients as well as the composition of the reference group [5] and a small number of cases included in each study. Thus, we perform this meta-analysis to evaluate the diagnosis value of serum Cyfra21-1 for NSCLC by pooling the published data.


 > Methods Top


Search strategy

All the articles associated with serum level of Cyfra21-1 in the diagnosis of NSCLC were searched in the PubMed, Medline and CNKI databases. The search items were: NSCLC, Cyfra21-1 and diagnosis.

Inclusion criteria

The inclusion criteria were focused on the aspects of patients included in the original study, diagnosis method, controls, and the outcomes. For patients, the patients included in this meta-analysis were pathology confirmed NSCLC patients; for the diagnosis method, the serum Cyfra21-1 array was the diagnosis tool; for the controls, the patients without the NSCLC were deemed as the controls; and for the outcomes, the original articles should provide patients number of the true positive, false positive, false negative and true negative. The paper should be published in English or Chinese.

Data extraction

The general information and exact data were extracted from the original individual studies by two reviews independently. The general information was included authors of the study, publication year, region, cut-off value of serum Cyfra21-1. The exacted data for extraction was true positive, false positive, false negative and true negative which was need for pool the diagnosis sensitivity, specificity, positive likely hood ratio (+lr), negative likely hood ratio (−lr), diagnosis odds ratio (dor) and summary receiver operating characteristic (sroc).

Statistics

The data were pooled and calculated by MetaDiSc 1.4 software (http://www.hrc.es/investigacion/metadisc.html). Before pooling the diagnosis specificity, +lr, −lr, dor and sroc the heterogeneity across the included individual studies was calculated. If the heterogeneity was found across the trials the pooled results were calculated based on random effect model. Otherwise, the fixed effect model was used. Heterogeneity was tested using the Z score and χ2 in which P < 0.1 was considered as statistically significant.


 > Results Top


Characteristics of included studies

After searching the databases, 17 studies with 4221 subjects were met the inclusion criteria and finally included in this meta-analysis. The publication year was range from 1994 to 2009 with smallest patient number of 48 and largest patient number of 1414. Six articles were come from China mainland, two from Taiwan, two from France, two from Poland and one form Israel, Spain, Croatia Japan and Korea each. The cut-off value of serum Cyfra21-1 was range from 1.72 to 3.7 ΅/L. The general information of the included articles was shown in [Table 1].
Table 1: The general characteristics of the included 17 studies


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Diagnosis sensitivity and specificity

Significant heterogeneity was found in the diagnosis sensitivity (P = 0.00) and specificity (P = 0.03). The diagnosis sensitivity and specificity was pooled by random effect model. The pooled diagnosis sensitivity and specificity were 0.72 (95% confidence interval [CI]: 0.70-0.73), 0.94 (95%CI: 0.93-0.95) [Figure 1].
Figure 1: Forest plot of sensitivity and specificity for Cyfra21-1 in the diagnosis of nonsmall cell lung cancer

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Pooled positive likely hood ratio and negative likely hood ratio and diagnosis odds ratio

Significant heterogeneity was found in the + lr (P = 0.00) −lr (P = 0.00) and dor (P = 0.00). So, the lr, −lr, and dor were calculated by random effect model. The pooled lr, −lr, and dor were 8.81 (95%CI: 6.36-12.22), 0.42 (95%CI: 0.32-0.55) [Figure 2] and 22.57 (95%CI: 13.89-36.68) [Figure 3].
Figure 2: Forest plot of positive likely hood ratio and negative likely hood ratio for Cyfra21-1 in the diagnosis of nonsmall cell lung cancer

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Figure 3: Forest plot of diagnosis odds ratio for Cyfra21-1 in the diagnosis of nonsmall cell lung cancer

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Area under the roc cure analysis

The roc curve was drawn and calculated by MetaDiSc 1.4 software. In this meta-analysis, the pooled area under the sroc curve was 0.95 with its stand error of 0.02 [Figure 4].
Figure 4: The area under the roc cure for Cyfra21-1 in the diagnosis of nonsmall cell lung cancer

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Publication bias

Publication bias was assessed by using the effect size of dor. Obvious publication bias was found for Cyfra21-1 in the diagnosis of NSCLC in this meta-analysis (P = 0.049) [Figure 5].
Figure 5: The funnel plot for evaluation the publication bias

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 > Discussion Top


According to the global cancer statistical analysis, lung cancer was estimated the leading cause of cancer-related deaths world-wide. [19],[20] The lung cancer was generally divided into two subgroups the NSCLC and the small cell lung carcinoma. And the NSCLC was taking part in almost of 80% of all the diagnosed lung cancer. The general prognosis of NSCLC was poor with 5 years survival rate <15% for patients with advanced stages. However the prognosis for patients with early stage treated by surgery was relative well.

Cyfra21-1 was a protein with a low molecular weight of 40 kDa. It is expressed and immunohistochemically detectable in the cytoplasm of epithelial tumor cells, especially in NSCLC. The Cyfra21-1 was firstly reported by Stieber et al. in 1993. [21] And thereafter, it was extensively studied as a biomarker for diagnosis of lung cancer. Some articles showed Cyfra21-1 a promising biomarker for lung cancer. [15],[17] But some other research papers indicated that the Cyfra21-1 had low diagnosis sensitivity in diagnosis of lung cancer. [8],[9] In this meta-analysis, 17 studies were included. And the pooled diagnosis sensitivity and specificity were 0.72 (95%CI: 0.70-0.73), 0.94 (95%CI: 0.93-0.95) which indicated that the serum Cyfra21-1 had a relative high power to distinguish NSCLC patients from patients without this disease.

A useful statistic in pooling studies by means of the ROC curve is the area under the curve (AUC) which summarizes the diagnostic performance as a single number. [22] a perfect test will have an AUC close to 1 and poor tests have AUCs close to 0.5. In our meta-analysis, the summary AUC of the sroc was 0.95 which was very close to 1.


 > Conclusion Top


The serum Cyfra21-1 was elevated in patients with NSCLC. And the serum Cyfra21-1 was a promising biomarker for diagnosis of NSCLC according to the results of this meta-analysis. But considering for the publication bias and heterogeneity across the included studies, the conclusion should be drawn with cautions and had its own limitations.

 
 > References Top

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Pan QR, Zhao X, Cao J, Cao YL. Study on the correlationship between CK19 mRNA and CyFRA21-1 in peripheral blood of lung cancer patients. Chin J Lab Diagn 2002;6:374-6.  Back to cited text no. 8
    
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Pujol JL, Boher JM, Grenier J, Quantin X. Cyfra 21-1, neuron specific enolase and prognosis of non-small cell lung cancer: Prospective study in 621 patients. Lung Cancer 2001;31:221-31.  Back to cited text no. 13
    
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Pavicevic R, Bubanovic G, Franjevic A, Stancic-Rokotov D, Samarzija M. CYFRA 21-1 in non-small cell lung cancer - standardisation and application during diagnosis. Coll Antropol 2008;32:485-98.  Back to cited text no. 15
    
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