Department of Infectious Diseases and Lab. of Liver Disease, Renmin Hospital, Hubei University of Medicine, 39 Chaoyang Zhong Road, Maojian District, Shiyan, 442000, China.
Clin Exp Med. 2019 May;19(2):235-243. doi: 10.1007/s10238-019-00550-1. Epub 2019 Mar 12.
Prognostic significance of serum microcystin in hepatocellular carcinoma has not been well investigated. The aim of the study was to reveal the relationship between serum microcystin-LR and prognosis in these patients. There were 650 early-stage hepatitis B-induced hepatocellular carcinoma patients, who were not affected by hepatitis C, cirrhosis, heavy drinking or excessive aflatoxin exposure. All of them underwent hepatectomy and were followed up for 5 years. Tumor relapse and overall death were recorded. Blood specimens were collected on admission and at the time of relapse. Serum levels of microcystin-LR and fluorescent oxidation products (FlOP_360, FlOP_320 and FlOP_400) were measured separately using enzyme-linked immunosorbent assay and fluorescence spectrometry. Multifactorial COX regression analysis suggested that serum microcystin-LR ≥ 0.97 ng/ml was associated with the increased risk of the tumor relapse (HR: 1.53, 95% CI: 1.35-1.77) and serum microcystin-LR ≥ 1.09 ng/ml was related to the higher risk of the overall death (HR: 1.58, 95% CI: 1.35-1.84) in the follow-up period. Furthermore, there was a linear relationship between serum level of microcystin-LR and serum levels of FlOP_360, FlOP_320 and FlOP_400 (P = 0.001, P = 0.023, P = 0.047). Serum levels of these fluorescent oxidation products were also higher in the patients with tumor relapse (P < 0.001, P < 0.001, P = 0.001) or overall death (P < 0.001, P = 0.001, P = 0.002) compared with the remaining patients. Serum microcystin-LR independently worsens the prognosis partly through promoting oxidative stress in patients with hepatocellular carcinoma.
血清微囊藻毒素在肝细胞癌中的预后意义尚未得到充分研究。本研究旨在揭示这些患者血清中微囊藻毒素-LR 与预后的关系。共有 650 例早期乙型肝炎相关性肝细胞癌患者，不受丙型肝炎、肝硬化、酗酒或过量黄曲霉毒素暴露的影响。所有患者均接受了肝切除术，并随访 5 年。记录肿瘤复发和总死亡情况。入院时和复发时采集血标本。分别采用酶联免疫吸附试验和荧光光谱法测定血清微囊藻毒素-LR 和荧光氧化产物（FlOP_360、FlOP_320 和 FlOP_400）水平。多因素 COX 回归分析提示，血清微囊藻毒素-LR≥0.97ng/ml 与肿瘤复发风险增加相关（HR：1.53，95%CI：1.35-1.77），血清微囊藻毒素-LR≥1.09ng/ml 与随访期间总死亡风险升高相关（HR：1.58，95%CI：1.35-1.84）。此外，血清微囊藻毒素-LR 水平与血清 FlOP_360、FlOP_320 和 FlOP_400 水平之间存在线性关系（P=0.001，P=0.023，P=0.047）。在肿瘤复发（P<0.001，P<0.001，P=0.001）或总死亡（P<0.001，P=0.001，P=0.002）的患者中，这些荧光氧化产物的血清水平也更高。血清微囊藻毒素-LR 通过促进肝细胞癌患者的氧化应激，独立地使预后恶化。
