Dickkopf-1 Promotes Angiogenesis and is a Biomarker for Hepatic Stem Cell-like Hepatocellular Carcinoma.
Dickkopf-1 Promotes Angiogenesis and is a Biomarker for Hepatic Stem Cell-like Hepatocellular Carcinoma.
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DOI：
10.3390/ijms23052801
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发表时间：
2022-03-03
影响因子：
5.6
通讯作者：
Kaneko S
中科院分区：
文献类型：
--
作者：
Suda T;Yamashita T;Sunagozaka H;Okada H;Nio K;Sakai Y;Yamashita T;Mizukoshi E;Honda M;Kaneko S
癌症干性因其导致的恶性程度和不良预后而引起关注。我们先前证明，肝干细胞样肝细胞癌（HpSC - HCC）与高血管侵犯和不良预后相关。Dickkopf - 1（DKK - 1）是一种Wnt信号调节因子，在HpSC - HCC中高表达。在此，我们评估了血清DKK - 1的诊断和预后潜力。与205例慢性肝病患者相比，391例肝细胞癌患者的血清DKK - 1水平显著升高。受试者工作特征曲线分析显示，诊断肝细胞癌以及预测3年生存率的DKK - 1最佳临界值分别为262.2 pg/mL和365.9 pg/mL。血清DKK - 1水平高的肝细胞癌患者预后不良。我们评估了抗DKK - 1抗体治疗对体内肿瘤生长的影响，以及重组DKK - 1对体外细胞增殖、侵袭和血管生成的影响。DKK - 1敲低减少了癌细胞的增殖、迁移和侵袭。DKK - 1补充促进了体外血管生成；这种作用被抗DKK - 1抗体消除。抗DKK - 1抗体与Huh7细胞共同注射抑制了它们在NOD/SCID小鼠体内的生长。因此，DKK - 1促进肝细胞癌细胞的增殖、迁移和侵袭，并激活血管内皮细胞的血管生成。DKK - 1是肝细胞癌的一种预后生物标志物，也是一种用于靶向治疗的功能分子。
Cancer stemness evinces interest owing to the resulting malignancy and poor prognosis. We previously demonstrated that hepatic stem cell-like hepatocellular carcinoma (HpSC-HCC) is associated with high vascular invasion and poor prognosis. Dickkopf-1 (DKK-1), a Wnt signaling regulator, is highly expressed in HpSC-HCC. Here, we assessed the diagnostic and prognostic potential of serum DKK-1. Its levels were significantly higher in 391 patients with HCC compared with 205 patients with chronic liver disease. Receiver operating characteristic curve analysis revealed the optimal cutoff value of DKK-1 to diagnose HCC and predict the 3-year survival as 262.2 and 365.9 pg/mL, respectively. HCC patients with high-serum DKK-1 levels showed poor prognosis. We evaluated the effects of anti-DKK-1 antibody treatment on tumor growth in vivo and of recombinant DKK-1 on cell proliferation, invasion, and angiogenesis in vitro. DKK-1 knockdown decreased cancer cell proliferation, migration, and invasion. DKK-1 supplementation promoted angiogenesis in vitro; this effect was abolished by an anti-DKK-1 antibody. Co-injection of the anti-DKK-1 antibody with Huh7 cells inhibited their growth in NOD/SCID mice. Thus, DKK-1 promotes proliferation, migration, and invasion of HCC cells and activates angiogenesis in vascular endothelial cells. DKK-1 is a prognostic biomarker for HCC and a functional molecule for targeted therapy.
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影响因子：
37.3
作者：
Chen L;Li M;Li Q;Wang CJ;Xie SQ
通讯作者：
Xie SQ
影响因子：
64.8
作者：
Glinka, A;Wu, W;Niehrs, C
通讯作者：
Niehrs, C
影响因子：
3.4
作者：
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Qin, Wenxin
影响因子：
6.1
作者：
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通讯作者：
Brandi, Giovanni
影响因子：
25.7
作者：
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通讯作者：
Paradis, Valerie