The value of serum Cyfra21‑1 as a biomarker in the diagnosis of patients with non‑small cell lung cancer: A meta‑analysis 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. KEY WORDS: Cyfra21‑1, diagnosis, meta‑analysis, nonsmall cell lung carcinoma *Chao Cui and Xin Sun contribute equally to this work
INTRODUCTION 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). Important progress in biochemical diagnostics for NSCLC with the introduction of determinations for the serum Cyfra21‑1 has been made. 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 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 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).
Journal of Cancer Research and Therapeutics - Volume 10 - Special Issue 2- 2014
Chao Cui*, Xin Sun1,*, Jun Zhang, Dong Han, Jundong Gu2 Departments of Thoracic Surgery and 1 Oncology, Tianjin Haihe Hospital, Tianjin 300350, PR China, 2Department of Thoracic Surgery, Tianjin Union Medical Center, Tianjin 300121, PR China For correspondence: Dr. Jundong Gu, Department of Thoracic Surgery, Tianjin Union Medical Center, Tianjin 300121, PR China. E‑mail: [email protected]
Access this article online Website: www.cancerjournal.net DOI: 10.4103/0973-1482.145835 PMID: *** Quick Response Code:
Cui, et al.: Cyfra21-1 and non-small cell lung cancer
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 2 in which P