Diagnostic value and prognosis assessment of ProGRP for small cell lung cancer / 中华检验医学杂志

ABSTRACT

Objective The purpose of this study was to discuss the clinical significance of serum levels of Pro-gastrin-releasing peptide (ProGRP) in diagnosis,therapy monitoring and prognosis in patients with small cell lung cancer (SCLC).Methods Clinical diagnostic trial.Serum levels of ProGRP were measured by ELISA assays in 413 SCLC patients,418 NSCLC,120 with benign pulmonary diseases patients and 200 healthy subjects.Patients were recuited by the Shanxi Cancer Hospital from Dec.2005 to Oct.2008.Three hundreds and sixty-eight patients with SCLC were followed up from Dec.2005 to Oct.2011.The receiver operating characteristic curves (ROC) was used to set the cut-off value of ProGRP and the area under ROC (ROC-AUC).The sensitivity and specificity of ProGRP were analyzed for diagnosing SCLC.The survival analysis was performed by the Kaplan-Meier method and Cox's proportional hazards model for multivariate analysis of prognosis.Results Using healthy subjects group as control,the largest Youden index point of ROC was used to set the cut-off values of ProGRP and NSE (45.3 ng/L and 12.4 ng/L).The ROC-AUC of ProGRP was 0.798 (95％ CI:0.746-0.850)the sensitivity and specificity were 79.2％,98.1％ respectively.The AUC of NSE was 0.786(95％ CI:0.726-0.746),the sensitivity and specificity were 71.9％,96.7％ respectively; Combing detection of ProGRP and NSE,the sensitivity and specificity were 88.1％,95.8％ respectively.Serum levels of ProGRP in healthy subjects,benign pulmonary diseases,NSCLC and SCLC groups were 6.9 (5.3-8.6),36.8 (26.3-43.4),21.3 (18.6-35.2) and 1758.7 (368.4-2967.3) μg/L respectively.The serum levels of ProGRP in SCLC groups were significantly higher than those in the healthy group,benign pulmonary diseases group and NSCLC group (H =103.66,P =0.000).Serum levels of ProGRP in SCLC at stage Ⅰ-],stage m,stage Ⅳ were 543.3 (256.8-843.2),1440.6 (1042.4-2543.3) and 1897.6 (1586.5-3958.7) μg/L,respectively (H =25.974,P =0.000).Serum levels of ProGRP in 165 SCLC patients with complete remission(CR) were significantly declined after treatment (U =11.65,P ＜ 0.01).The levels of ProGRP in 146 SCLC patients with partial remission(PR) slowly decreased (U =9.17,P ＜ 0.01).Thirty-nine cases with progressive disease (PD)and 63 cases with stable disease(SD) presented elevated ProGRP levels (U =3.314,P ＜ 0.001 ; U =2.54,P ＜ 0.01,respectively).By the end of October 31st 2011,a total of 368 cases with SCLC were followedup.Ratio of follow-up was 89.1％.There were 56 deaths in 119 SCLC patients with ProGRP ＜ 1000 μg/L (median time =16.0 months,4-23 months) ; 159 deaths in 249 with ProGRP ＞ 1000 μg/L (median survival time =12.0 months,2-18 months).Median survival time of the two groups showed significant differences(x2 =11.04,P =0.001).Multivariate analysis by Cox's proportional hazards model revealed that ProGRP was independent prognostic factor related to the overall survival (OS) of SCLC patients.Conclusions The serum ProGRP is valuable tumor marker for diagnosis,treat monitoring and prognosis of SCLC.It's important to predict relapses and recurrence of diseases earlier,instruct therapy and prognosis assessment.