CYFRA 21-1 antigen

Gene expression profile analysis of lung cancers revealed the transactivation of an immunoglobulin-like molecule Nectin-4 in the majority of non-small cell lung cancers (NSCLC). Immunohistochemical staining of 422 NSCLCs showed that a high level of Nectin-4 expression was associated with poor prognosis for NSCLC patients (P < 0.0001), and multivariate analysis confirmed its independent prognostic value (P < 0.0001). We established an ELISA to measure serum Nectin-4 and found that serum Nectin-4 levels were significantly higher in NSCLC patients than in healthy volunteers. The proportion of the serum Nectin-4-positive cases was 88 of 164 (53.7%) NSCLCs, whereas only 3 of 131 (2.3%) healthy volunteers were falsely diagnosed as positive, which was superior to carcinoembryonic antigen (CEA) and cytokeratin 19-fragment (CYFRA21-1) in sensitivity and specificity. A combined ELISA for both Nectin-4 and CEA increased sensitivity and classified 65.0% of lung adenocarcinomas as positive with false-positive rate of 4.6%. The use of both Nectin-4 and CYFRA21-1 classified 68.3% of lung squamous cell carcinomas as positive with false-positive rate of 6.1%. Treatment of lung cancer cells with small interfering RNAs against Nectin-4 suppressed its expression and cell growth. In addition, exogenous expression of Nectin-4 increased the lamellipodia formation and the invasive ability of mammalian cells through activation of small GTPase Rac1. Nectin-4 might play a significant role in lung carcinogenesis, and it should be a new candidate serum and tissue biomarker, as well as a therapeutic target. [Cancer Res 2009;69(16):6694-703]

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 (+Ir), negative likely hood ratio (-Ir), 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, +ft, -Ir and dor were 0.72 (95% confidence interval [Cl]: 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.