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.
Highlights
Hepatocellular carcinoma (HCC) is the most prevalent malignant disease with the second highest mortality rate worldwide [1]
We found that the serum Apolipoprotein A1 (ApoA-1) level was significantly lower in hepatocellular carcinoma (HCC) patients with tumor recurrence, and was an independent indicator of tumor-free survival and overall survival
The serum ApoA-1 level was significantly lower in HCC patients with recurrent disease compared with patients without recurrence (1.09 ± 0.02 g/L vs. 1.17 ± 0.02 g/L, p
Summary
Hepatocellular carcinoma (HCC) is the most prevalent malignant disease with the second highest mortality rate worldwide [1]. Surgery remains the most effective treatment for HCC; the prognosis of HCC remains unsatisfactory because of high recurrence and metastasis post-surgery [2, 3]. A pilot study found that the serum ApoA-1 level was significantly lower in patients with HCC [17, 18] and lower still in HCC patients with portal tumor thrombosis [19]. These findings implied that ApoA-1 might play a significant role in tumorigenesis and cancer progression of HCC. Limited data were available on the clinical significance of serum ApoA-1 levels in HCC, and the mechanism of ApoA-1 involvement in HCC progression remained to be elucidated
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