Apolipoprotein A1: a novel serum biomarker for predicting the prognosis of hepatocellular carcinoma after curative resection
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Xiao-Lu Ma1,*, Xing-Hui Gao1,*, Zi-Jun Gong2,*, Jiong Wu1, Lu Tian1, Chun-Yan Zhang1,Yan Zhou1, Yun-Fan Sun2, Bo Hu2, Shuang-jian Qiu2, Jian Zhou2, Jia Fan2, Wei Guo1, Xin-Rong Yang2
1Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, P. R. China
2Department 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
Xin-Rong Yang, email: firstname.lastname@example.org
Wei Guo, email: email@example.com
Keywords: Apolipoprotein A1, hepatocellular carcinoma, serum biomarker, prognosis, circulating tumor cell
Received: December 13, 2015 Accepted: September 12, 2016 Published: September 23, 2016
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.
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