Lv Yang, Han Xu, Zhang Chunyan, Fang Yuan, Pu Ning, Ji Yuan, Wang Dansong, Xuefeng Xu, Lou Wenhui
Department of General SurgeryZhongshan Hospital, Fudan University, Shanghai, China.
Department of Clinical LaboratoryZhongshan Hospital, Fudan University, Shanghai, China.
Endocr Connect. 2018 Jan;7(1):169-178. doi: 10.1530/EC-17-0276. Epub 2017 Nov 30.
Chromogranin A (CgA) and neuron-specific enolase (NSE) are important markers for neuroendocrine tumors; however, the clinical value of combining these markers has not been well studied. In this study, we investigated the utility of each marker individually and in combination for patients with nonfunctional pancreatic neuroendocrine tumors (NF-pNETs).
In this study, NF-pNET patients and controls were recruited from December 2011 to March 2016; 784 serum samples from peripheral vein were collected. The clinical characteristics and biomarker values of all the individuals were recorded and analyzed. Tumor burdens were calculated by CT/MRI scan. Receiver-operating characteristic curves were constructed to assess the diagnostic predictive values; sensitivity and specificity were calculated to determine the cut-off value. Therapeutic responses reflected on the changes of the biomarkers' concentration were assessed by the RECIST criterion. Clinical relations between the prognosis and the biomarker values were also analyzed. Statistical significance was defined as value less than 0.05.
Among the 167 NF-pNETs patients, 82 were males (49.1%) and the mean age was 50.0 (17.4). The mean CgA values of G1, G2 and G3 NF-pNENs were 75, 121 and 134 μg/L ( < 0.05), respectively. In NF-pNETs, CgA correlated with the WHO tumor grade (WHO G1 vs G2, < 0.05); the linear regression relationships were found between the tumor burdens (both in pancreas and liver) and CgA concentration ( < 0.001); changes in CgA and NSE concentrations also reflect treatment response ( < 0.001).
CgA and NSE are important diagnostic and follow-up markers in patients with NF-pNETs. The combined monitoring of CgA and NSE possesses more accuracy than individual values of CgA and NSE at predicting prognosis and disease progression.
嗜铬粒蛋白A（CgA）和神经元特异性烯醇化酶（NSE）是神经内分泌肿瘤的重要标志物；然而，联合使用这些标志物的临床价值尚未得到充分研究。在本研究中，我们调查了这些标志物单独及联合应用于无功能性胰腺神经内分泌肿瘤（NF-pNETs）患者的效用。
本研究于2011年12月至2016年3月招募了NF-pNET患者及对照；采集了784份外周静脉血清样本。记录并分析了所有个体的临床特征和生物标志物值。通过CT/MRI扫描计算肿瘤负荷。构建受试者操作特征曲线以评估诊断预测价值；计算敏感性和特异性以确定临界值。根据实体瘤疗效评价标准（RECIST）评估生物标志物浓度变化所反映的治疗反应。还分析了预后与生物标志物值之间的临床关系。统计学显著性定义为P值小于0.05。
167例NF-pNETs患者中，男性82例（49.1%），平均年龄为50.0（17.4）岁。G1、G2和G3级NF-pNENs的平均CgA值分别为75、121和134μg/L（P<0.05）。在NF-pNETs中，CgA与世界卫生组织（WHO）肿瘤分级相关（WHO G1与G2相比，P<0.05）；在胰腺和肝脏的肿瘤负荷与CgA浓度之间发现了线性回归关系（P<0.001）；CgA和NSE浓度的变化也反映了治疗反应（P<0.001）。
CgA和NSE是NF-pNETs患者重要的诊断和随访标志物。联合监测CgA和NSE在预测预后和疾病进展方面比CgA和NSE的单独值具有更高的准确性。
