Clinical Significance Of Lung Cancer Related Serum Biomarkers: ProGRP、SCC-Ag、Cyfra21-1 And CEA

Background Lung cancer is one of the leading causes of death from malignancy worldwide. The use of non-invasive tools for screening and monitoring has gained increasing interest and the clinical applicability of reliable, tumor-related substances that can be detected as tumor markers in easily accessible blood is subject of intense investigation. The aim of this retrospective study was to assess the clinical value of Pro-gastrin Releasing Peptide (ProGRP)、Squamous Cell Carcinoma Antigen (SCC-Ag)、cytokeratin 19 fragment antigen 21-1(Cyfra21-1) and Carcino-Embryonic antigen (CEA)in diagnosis、pathology、clinical stage and genetic mutation of lung cancer in Chinese patients. Methods According to the inclusion/exclusion criteria,we selected two hundred and twenty-one subjects in outpatient and inpatient of Peking Union College Hospital from January 2013 to October 2014. Lung cancer subjects who had received chemotherapy or radiotherapy or surgical resection were excluded, as were subjects who had multiple malignancies icluding multiple lung cancer. The serum levels of four tumor markers (ProGRP、SCC-Ag、Cyfra21-1 and CEA) were mesured using commercially available immunoassays before lung cancer treatment. Serum levels of ProGRP、SCC-Ag、Cyfra21-1 and CEA higher than 65pg/ml、1.5ng/ml、2.08ng/ml and 5ng/ml, respectively, were considered as positive according to the manufacture’s instructions. The sensitivities、specificities、Positive Predictive Value[PPV]、Negative Precitive Value (NPV) and the areas under the receiver operating characteristic curve(AUC-ROC) of four tumor markers were analyzed for diagonsing Lung Cancer. Nonparametric rank sum test (Mann-Whitney U test for two-sample, Kruskal-Wallis H test for multiple-sample) assessed the distribution of the serum tumor markers levels. Results The diagnosis classification was lung cancer in 113 subjects and benign lung diseases in 108 subjects. Kruskal-Wallis H test of independent sample confirmed that serum levels of ProGRP、SCC-Ag、Cyfra21-1 in lung cancer were significantly higher than those in benign diseases group (p= 0.004、0.001 and 0.005, respectively).The sensitivity of serum Cyfra21-1 to diagonose lung cancer was 56.6%, the specificity 91%,the AUC-ROC 0.658. The sensivity of the panel of tumor markers (including ProGPR、 SCC-Ag、Cyfra21-1 and CEA) to diagnose lung cancer was 72.9%, the specitivity 75%, the AUC-ROC 0.739. In the lung cancer group, the sensitivity of SCC-Ag to diagnose squamous cell lung cancer was 87.9%, the specificity 91%, the AUC-ROC 0.968; the sensivity of ProGRP to diagnose small cell lung cancer was 93.8%, the specificity 99.0%, the AUC-ROC 0.990. In small cell lung cancer subjects, the levels of ProGRP in limited-disease small cell lung cancer (LD-SCLC) were significantly higher than extensive-disease small cell lung cancer (ED-SCLC) (P=0.000). The clinicopathological charateristics of each patient were compared among the subgroups stratified by the EGFR gene status. The level of serum CEA in who harbored the EGFR mutation gene was significantly higher than the subjects who carried the EGFR wild gene (P=0.000).Conclusion This panel of serum tumor markers (ProGRP、SCC-Ag、Cyfra21-1 and CEA) increased the diagnostic specificity and sentivity among high-risk lung cancer. The high level of serum ProGRP predicts the ED-SCLC. High serum CEA can identify a clinical feature of patients with EGFR-mutation lung adenocarcinoma.