Microcystin-LR in peripheral circulation worsens the prognosis partly through oxidative stress in patients with hepatocellular carcinoma.

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.