Apolipoprotein A1: a novel serum biomarker for predicting the prognosis of hepatocellular carcinoma after curative resection

// Xiao-Lu Ma 1, * , Xing-Hui Gao 1, * , Zi-Jun Gong 2, * , Jiong Wu 1 , Lu Tian 1 , Chun-Yan Zhang 1 ,Yan Zhou 1 , Yun-Fan Sun 2 , Bo Hu 2 , Shuang-jian Qiu 2 , Jian Zhou 2 , Jia Fan 2 , Wei Guo 1 , Xin-Rong Yang 2 1 Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, P. R. China 2 Department of Liver Surgery, Liver Cancer Institute, Zhongshan hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, P. R. China * These authors have contributed equally to this work Correspondence to: Xin-Rong Yang, email: yang.xinrong@zs-hospital.sh.cn Wei Guo, email: guo.wei@zs-hospital.sh.cn Keywords: Apolipoprotein A1, hepatocellular carcinoma, serum biomarker, prognosis, circulating tumor cell Received: December 13, 2015 Accepted: September 12, 2016 Published: September 23, 2016 ABSTRACT As a major protein constituent of high density lipoprotein, Apolipoprotein A1 (ApoA-1) might be associated with cancer progression. Our study investigated the serum ApoA-1 level for the prognosis of 443 patients with hepatocellular carcinoma (HCC) and its effects on tumor cells. We found that the serum ApoA-1 level was significantly lower in HCC patients with tumor recurrence, and was an independent indicator of tumor-free survival and overall survival. Low serum ApoA-1 levels were significantly associated with multiple tumors and high Barcelona Clinic Liver Cancer stage. The circulating tumor cell (CTC) levels were significantly higher in patients with low serum ApoA-1 compared with those with high serum ApoA-1 levels (4.03 ± 0.98 vs. 1.48 ± 0.22; p =0.001). In patients with detectable CTCs, those with low ApoA-1 levels had higher recurrence rates and shorter survival times. In vitro experiments showed that ApoA-1 can inhibit tumor cell proliferation through cell cycle arrest and promote apoptosis through down regulating mitogen-activated protein kinase (MAPK) pathway. In addition, ApoA-1 might impair extracellular matrix degradation properties of tumor cells. Taken together, our findings indicate that decreased serum ApoA-1 levels are a novel prognostic factor for HCC, and the role of ApoA-1 in inhibition of proliferation and promotion of apoptosis for tumor cells during their hematogenous dissemination are presumably responsible for the poor prognosis of patients with low ApoA-1 levels. Furthermore, AopA-1 might be a promising therapeutic target to reduce recurrence and metastasis for HCC patients after resection.