Zhang Chuan, Huang Yue, Long Jiang, Yao Xiaochen, Wang Jun, Zang Shimin, Qu Wei, Wang Feng
Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.
Department of Pathology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.
Oncol Lett. 2019 Feb;17(2):1497-1504. doi: 10.3892/ol.2018.9795. Epub 2018 Dec 5.
The aim of the present study was to assess the clinical value of serum chromogranin A (CgA) levels in patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) and to compare them with tumour expression of CgA. A total of 109 consecutive patients with confirmed GEP-NENs were enrolled in this prospective study between December 2012 and August 2016, including 73 patients with primary or recurrent GEP-NENs and 36 patients with GEP-NENs that were treated following surgery. Furthermore, 30 patients with benign gastrointestinal diseases and 30 healthy volunteers served as control groups. Serum CgA levels were measured by ELISA, using different reference values, in order to evaluate its diagnostic efficacy. Serum neuron-specific enolase was also measured to evaluate its diagnostic efficacy and analyse its association with serum CgA levels. The levels of CgA, synaptophysin and neural cell adhesion molecule 1 in the tumour tissue were assessed by immunohistochemical assays. The results indicated that serum CgA levels were significantly higher in patients with GEP-NENs compared with the control groups (P<0.05). No association was observed between serum CgA levels and tumour grade (G1, G2 and G3), but serum CgA levels differed significantly between patients with GEP-NENs of different origins (P<0.05). A serum CgA cut-off value of 85.3 ng/ml was associated with high sensitivity (64.4%) and specificity (92.7%). Different reference values were recommended for NENs of different origins, with serum CgA cut-off values of 96.72, 51.13 and 86.19 ng/ml for the stomach, intestines and pancreas, respectively. The serum CgA levels were consistent with the CgA expression in the tumour. In conclusion, serum CgA may serve as a circulating pathological biomarker for the diagnosis of GEP-NENs. The use of different reference values for different tumour origins may improve the diagnostic efficacy of CgA for GEP-NENs. A cut-off value of 85.3 ng/ml is recommended in the Chinese population.
本研究旨在评估血清嗜铬粒蛋白A（CgA）水平在胃肠胰神经内分泌肿瘤（GEP-NENs）患者中的临床价值，并将其与肿瘤组织中CgA的表达进行比较。2012年12月至2016年8月期间，共有109例确诊为GEP-NENs的连续患者纳入了这项前瞻性研究，其中包括73例原发性或复发性GEP-NENs患者以及36例接受手术后治疗的GEP-NENs患者。此外，30例患有良性胃肠道疾病的患者和30名健康志愿者作为对照组。采用酶联免疫吸附测定法（ELISA），使用不同的参考值来测量血清CgA水平，以评估其诊断效能。还测量了血清神经元特异性烯醇化酶，以评估其诊断效能并分析其与血清CgA水平的相关性。通过免疫组织化学测定法评估肿瘤组织中CgA、突触素和神经细胞黏附分子1的水平。结果表明，与对照组相比，GEP-NENs患者的血清CgA水平显著更高（P<0.05）。未观察到血清CgA水平与肿瘤分级（G1、G2和G3）之间存在关联，但不同起源的GEP-NENs患者之间血清CgA水平存在显著差异（P<0.05）。血清CgA临界值为85.3 ng/ml时，具有较高的敏感性（64.4%）和特异性（92.7%）。对于不同起源的神经内分泌肿瘤，建议使用不同的参考值，胃、肠和胰腺的血清CgA临界值分别为96.72、51.13和86.19 ng/ml。血清CgA水平与肿瘤组织中CgA的表达一致。总之，血清CgA可作为诊断GEP-NENs的循环病理生物标志物。针对不同肿瘤起源使用不同的参考值可能会提高CgA对GEP-NENs的诊断效能。建议中国人群的临界值为85.3 ng/ml。
