Apolipoprotein A1: a novel serum biomarker for predicting the prognosis of hepatocellular carcinoma after curative resection.
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.
Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.
Xiao-Lu
XL
Ma
Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.
Xing-Hui
XH
Gao
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.
Zi-Jun
ZJ
Gong
Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.
Jiong
J
Wu
Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.
Lu
L
Tian
Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.
Chun-Yan
CY
Zhang
Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.
Yan
Y
Zhou
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.
Yun-Fan
YF
Sun
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.
Bo
B
Hu
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.
Shuang-Jian
SJ
Qiu
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.
Jian
J
Zhou
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.
Jia
J
Fan
Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.
Wei
W
Guo
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.
Xin-Rong
XR
Yang
D016632:Apolipoprotein A-I / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis / Q000601:surgery; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009360:Neoplastic Cells, Circulating / Q000473:pathology; D017063:Outcome Assessment, Health Care / Q000379:methods; D011379:Prognosis
D016632:Apolipoprotein A-I; D014408:Biomarkers, Tumor
Apolipoprotein A1; circulating tumor cell; hepatocellular carcinoma; prognosis; serum biomarker
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