Apolipoprotein A1: a novel serum biomarker for predicting the prognosis of hepatocellular carcinoma after curative resection.
Apolipoprotein A1: a novel serum biomarker for predicting the prognosis of hepatocellular carcinoma after curative resection.
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载脂蛋白A1：预测肝细胞癌根治性切除术后预后的新型血清生物标志物
DOI：
10.18632/oncotarget.12203
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发表时间：
2016-10-25
期刊：
影响因子：
--
通讯作者：
Yang XR
中科院分区：
文献类型：
--
作者：
Ma XL;Gao XH;Gong ZJ;Wu J;Tian L;Zhang CY;Zhou Y;Sun YF;Hu B;Qiu SJ;Zhou J;Fan J;Guo W;Yang XR
载脂蛋白A1(ApoA-1)作为高密度脂蛋白的主要蛋白质组分，可能与肿瘤的进展有关。本研究探讨了443例肝细胞癌患者血清载脂蛋白A-1水平对预后的影响及其对肿瘤细胞的影响。我们发现血清ApoA-1水平在有肿瘤复发的肝细胞癌患者中显著降低，并且是无瘤生存和总生存的独立指标。血清ApoA-1水平低与多发性肿瘤和巴塞罗那临床肝癌分期高显著相关。血清载脂蛋白A-1水平低的患者外周血肿瘤细胞水平显著高于载脂蛋白A-1水平高的患者(4.03±0.98vs.1.48±0.22；P=0.001)。在可检测到CTC的患者中，ApoA-1水平低的患者复发率更高，生存时间更短。体外实验表明，ApoA-1通过细胞周期阻滞抑制肿瘤细胞增殖，通过下调丝裂原活化蛋白激酶(MAPK)途径促进细胞凋亡。此外，ApoA-1可能会损害肿瘤细胞的细胞外基质降解特性。综上所述，我们的研究结果表明，血清ApoA-1水平的降低是一种新的肝癌预后因素，ApoA-1在肿瘤细胞血行播散过程中抑制肿瘤细胞增殖和促进肿瘤细胞凋亡的作用可能是ApoA-1水平低的患者预后不良的原因。此外，AOPA-1有可能成为减少肝癌患者术后复发和转移的治疗靶点。
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.