胃泌素释放肽前体对小细胞肺癌诊治的临床意义

目的探讨血清胃泌素释放肽前体(ProGRP)的生物学特性及其对小细胞肺癌(SCLC)的诊断、病情监测、疗效评估、预后判断的临床意义以及ProGRP与神经元特异性烯醇化酶(NSE)水平之间的相关性,为SCLC的预防和治疗提供科学依据。方法收集肺癌患者1221例,健康对照组500名,采用酶联免疫吸附法检测治疗前后肺癌患者及健康对照者血清ProGRP和NSE水平,同时肺癌患者还进行相关的影像学检查。结果270例治疗前SCLC患者血清ProGRP中位值为544.48pg/ml,敏感性为84.07%,均明显高于非小细胞肺癌(NSCLC)组及健康对照组,差异均有统计学意义(P<0.01)。270例SCLC患者随着临床分期期别的增加,Pro-GRP水平大于界值例数也明显增加,检出敏感性增加(P<0.01)。270例SCLC患者疗效评价获得完全缓解者ProGRP水平明显下降,无变化者及病情进展者ProGRP水平均明显高于界值(P<0.01)。治疗后在24个月之内出现复发、转移患者,血ProGRP水平明显高于治疗后健康生存者,且高于治疗前血ProGRP水平(P<0.01)。ProGRP水平的变化与影像学所示的肿瘤大小具有明显的相关性,ProGRP和NSE水平对SCLC的联合检测呈正相关(r=0.243,P<0.01)。结论血清ProGRP检测可作为SCLC诊断、病情监测、疗效评估、预后判断的敏感和特异性指标,与NSE联合检测可进一步提高敏感性。

Clinical significance of ProGRP in diagnosis and treatment of SCLC

Objective To explore the biological characteristic of serum ProGRP and its clinical significance in diagnosis, monitoring, treatment evaluation and prognosis of SCLC, and to identify the correlation between ProGRP and NSE level in search of a tumor marker with high sensitivity and specificity, which would provide a scientific basis for SCLC prevention and treatment. Methods Between October 2005 and October 2007, 1221 cases of lung cancer patients treated in Shanxi Cancer ttospital and a cnntemporary cohort of 500 healthy controls were recruited. Serum Pro- GRP and NSE level in hmg cancer patients before and after treatment as well as healthy subjects were detected with ELISA. Meanwhile, imaging studies were performed in lung cancer patients. SPSS11.0 software package was applied to process statistically. Results The mediam level of serum ProGRP in 270 SCLC patients before treatment was 544.48 pg/ml with 84.07% sensitivity, which was significantly higher compared with the NSCLC group and healthy control group （P〈0.01）. Among the SCLC patients, elevated ProGRP was found more in those with higher clinical stages. This difference was sensitive and significant in group comparison of sensitivity （P〈0.01）. The level of ProGRP dramatically decreased in treatment-responders but remained higher than normal in those not responsive to treatment or progression （P〈0.01 respectively）. SCLC patients who survived and remained good tumor control for 3, 6, 12 and 24 months after treatment showed comparable, lower-than-normal level of ProGRP （P〉0.05）. However, those with recurrence, metastasis or progression within 24 months after treatment had higher level of ProGRP than healthy survivors and even compared significantly with the level prior to treatment （P〈0.01 respectively）. Changes in ProGRP level was found to significantly correlate with tumor size as shown by imaging, decreasing with reduced size or disappearance of tumor and becoming even higher than pre-treatment level when metastatsis occurred. Combined tests of ProGRP and NSE （r= 0.243, P〈0.01） but not ProGRP and CEA （r=0.014, P=0.706） were found to significantly correlated with SCLC detection. Conclusion Serum ProGRP can be used as a sensitive and specific index for diagnosis, monitoring, treatment evaluation and prognosis of SCLC. Addition of NSE test may further improve the sensitivity of detection.