Tsai Hui-Jen, Hsiao Chin-Fu, Chang Jeffrey S, Chen Li-Tzong, Chao Ying-Jui, Yen Chia-Ju, Shan Yan-Shen
National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.
Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Front Oncol. 2021 Nov 12;11:741096. doi: 10.3389/fonc.2021.741096. eCollection 2021.
Chromogranin A (CgA) is a non-specific biomarker excreted by neuroendocrine tumor (NET) cells. Elevation of circulating CgA level can be detected in gastroenteropancreatic (GEP)-NET patients and has been shown to correlate with tumor burden. The prognostic and predictive roles of CgA level and the change of CgA level are controversial. In this study, we retrospectively analyzed 102 grade 1/2 GEP-NET patients with available baseline or serial follow-up CgA levels from the National Cheng Kung University Hospital to evaluate the association between circulating CgA level and the tumor extent, overall survival (OS), and tumor response prediction. The baseline characteristics, baseline CgA level, and change of CgA level during follow-up and their association was analyzed. Sixty cases had baseline CgA levels available prior to any treatment and ninety-four cases had serial follow-up CgA levels available during treatment or surveillance. Baseline CgA levels were associated with stage and sex. Higher baseline CgA levels were associated with worse OS after adjusting for sex, stage, grade, primary site, and functionality (hazard ratio=13.52, 95% confidence interval (CI), 1.06-172.47, =0.045). The cross-sectional analysis for the change of CgA level during follow-up showed that a ≥ 40% increase of CgA meant a higher probability of developing tumor progression or recurrence than those with a < 40% increase of CgA level (odds ratio=5.04, 95% CI, 1.31-19.4, =0.019) after adjusting for sex, age, grade, stage, and functionality. Our study results suggest that CgA may be a predictive marker for tumor burden, OS, and tumor progression in GEP-NET patients.
嗜铬粒蛋白A（CgA）是一种由神经内分泌肿瘤（NET）细胞分泌的非特异性生物标志物。在胃肠胰（GEP）-NET患者中可检测到循环CgA水平升高，且已证明其与肿瘤负荷相关。CgA水平及其变化的预后和预测作用存在争议。在本研究中，我们回顾性分析了102例来自国立成功大学医院、有可用基线或系列随访CgA水平的1/2级GEP-NET患者，以评估循环CgA水平与肿瘤范围、总生存期（OS）及肿瘤反应预测之间的关联。分析了基线特征、基线CgA水平、随访期间CgA水平的变化及其关联。60例患者在任何治疗前有可用的基线CgA水平，94例患者在治疗或监测期间有系列随访CgA水平。基线CgA水平与分期和性别相关。在调整性别、分期、分级、原发部位和功能后，较高的基线CgA水平与较差的OS相关（风险比=13.52，95%置信区间（CI），1.06 - 172.47，P = 0.045）。随访期间CgA水平变化的横断面分析显示，在调整性别、年龄、分级、分期和功能后，CgA水平升高≥40%的患者发生肿瘤进展或复发的可能性高于CgA水平升高<40%的患者（优势比=5.04，95%CI，1.31 - 19.4，P = 0.019）。我们的研究结果表明，CgA可能是GEP-NET患者肿瘤负荷、OS和肿瘤进展的预测标志物。
