Application of serum levels of pro-gastrin releasing peptide, tissue polypeptide specific antigen and neuron specific enolase in therapy monitoring in small cell lung cancer patients / 中华检验医学杂志

ABSTRACT

Objective To evaluate the clinical significance of serum levels of ProGRP, TPS and NSE in diagnosis and therapy monitoring in small cell lung cancer patients. Methods The levels of serum ProGRP, TPS and NSE in 51 SCLC patients (SCLC group), 60 benign pulmonary disease patients (benign disease group ) and 60 healthy people (healthy group ) were determined using chemiluminescent immunoassay, ELISA and electrochemiluminescent immunoassay respectively. Blood samples were collected and detected prior to therapy, before the second course of chemotherapy and the third course of chemotherapy consecutively in all the 51 SCLC patients. Results The serum ProGRP, TPS and NSE concentrations prior to chemotherapy in limited stage SCLC (LSCLC) were 136. 9(22.8-631.7)ng/L, 78. 2(56.4-114.6) U/L and 28.1(20.9-46.1)μg/L, respectively; And in extensive stage SCLC patients (ESCLC) were 1 106.6(41.2-2161.1) ng/L, 230. 9( 143.5-259.0) U/L and 81.1 (34.3-140.0)μg/L, respectively. The serum concentrations of the 3 markers in benign disease group were 19. 7 ( 9. 5-29. 1 )ng/L, 48. 7 ( 17.9-95.4) U/L and 12. 1(1.2-13.9) μg/L; and in healthy group were 20.3(10.7-30.6) ng/L, 50.3(19.5-70.7) U/L and 11.7 (1.1-13.4)μg/L, respectively. The Kruskal-Wallis test showed significantly statistical difference in different groups of the 3 tumor markers, Chi-Square were 51. 368,36. 532 and 81. 645( P ＜0. 01 ). Significant statistically differences showed when the concentrations of the 3 marks of the 2 control group were compared with that of the LSCLC group ( U =491, 827, 609 and 476, 831, 585,respectively, P ＜ 0. 05 ). Differences were also statistically significant when the 2 control group compared with that of the ESCLC group ( U = 314,532,456 and 302,553,430, respectively, P ＜ 0. 01 ). The AUC of ProGRP was 0.832 +0.029(95% CI0.774-0.890). When cutoff value of ProGRP set as 37.7 ng/L, the diagnostic sensitivity, specificity, positive predictive value, negative predictive value and Youden's index were 71% (36/51), 97% (116/120), 90% (36/40), 89% ( 116/131 ) and 67%, respectively; show good detection performance. The sensitivity increased to 92%, 86%, 92% and 88%, when combination detection of ProGRP + TPS + NSE, ProGRP + TPS, ProGRP + NSE and TPS + NSE were used, and the specificities were 77%, 77% , 92% and 77% accordingly. The Fridman test showed significantly statistical difference in the 3 tumor markers at different stages of treatment, x2 were 49. 120, 10. 614 and 44. 392, P ＜0. 01. After the first chemotherapy course, all the tumor marker levels except TPS decreased significantly in comparison with the pretreatment concentrations. However, only ProGRP levels showed a progressive drop during the two consecutive courses of therapy, and the median concentrations were 68.0 ( 18. 6-158.4 ) and 21.0( 14. 9-63.5) ng/L (compared to the level before therapy,Z=-4. 889 and -5. 594, P ＜0. 01 ). The median of serum TPS increased slightly to 105.2 (54. 1-181.2 ) U/L after the first chemotherapy course (Z=-1.248, P＞0.05), and decreased significantly to 79.0(48.7-155.3) U/L after the second chemotherapy course (Z=-2.484, P＜0. 05 ). As to the NSE, the median concentration decreased to 11.8(8.0-16.0)μg/L after the first chemotherapy course ( Z= - 5. 568, P ＜ 0. 01 ). However, the median was 10. 6(9.0-12.7)μg/L, which showed no significant decrease after the second chemotherapy course (Z=-1.851, P＞0.05).Forty-six SCLC patients evaluated as clinical remission ( 3 CR and 43 PR) after the second chemotherapy course, among them there were 38 patients (83%) with normal serum ProGRP, TPS and NSE level ( 19 patients) or with only 1 abnormal tumor level ( 19 patients). There were only 2 patients with all abnormal serum ProGRP, TPS and NSE level, and both patients were evaluated as clinical PD. Two patients with 2 abnormal tumors results were classified as SD, the only 1 patient without therapy evaluation also had 2 abnormal tumor marker results. Conclusions The serum ProGRP, TPS and NSE are valuable tumor markers for diagnosis and treat monitoring of SCLC, particularly the ProGRP + NSE shows the highest clinical value. Combing detection of the 3 tumor markers are valuable for therapy monitoring and prognosis in SCLC patients.