SALL4 is a novel therapeutic target in intrahepatic cholangiocarcinoma.
SALL4 is a novel therapeutic target in intrahepatic cholangiocarcinoma.
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DOI：
10.18632/oncotarget.4862
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发表时间：
2015-09-29
期刊：
影响因子：
--
通讯作者：
Wan T
中科院分区：
文献类型：
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作者：
Deng G;Zhu L;Huang F;Nie W;Huang W;Xu H;Zheng S;Yi Z;Wan T
肝内胆管细胞癌（ICC）是胆道系统最常见和最致命的疾病，由于其预后差。Sal样蛋白4（SALL 4）是一种干细胞标志物，已被确定为侵袭性肝细胞癌（HCC）的潜在靶点。在我们的研究中，纳入了175例ICC病例，平均年龄为55岁，其中53%（93/175）为男性。同时收集28例癌旁非肿瘤组织。SALL 4阳性免疫反应性检测在102个ICC病例（58%），而所有28个相邻组织显示阴性染色。单因素分析显示，SALL 4阳性ICC患者的淋巴结转移（P = 0.0460）、血管侵犯（P < 0.0001）和神经侵犯（P <0.0001）明显高于阴性ICC患者。此外，强SALL 4阳性病例（n = 7，5个月）的总生存期分别短于中度SALL 4阳性病例（n = 46，9个月）或SALL 4阴性病例（n = 73，7个月）。我们的数据还表明，SALL 4可能参与调控上皮间质转化（EMT）在ICC。这些结果首次表明SALL 4在ICC中的致癌作用。因此，SALL 4可能成为ICC的一个有希望的治疗靶点。
Intrahepatic cholangiocarcinoma (ICC) is the most common and deadly disease of the biliary tree due to its poor prognosis. Sal-like protein 4 (SALL4), a stem cell marker, has been identified as a potential target for aggressive hepatocellular carcinoma (HCC). In our study, 175 ICC cases with an average age of 55 years were included, and 53% (93/175) were male. And 28 adjacent non-tumor tissues were also collected. The SALL4-positive immunoreactivity was detected in a total of 102 ICC cases (58%), whereas all 28 adjacent tissues showed negative staining. Univariate analysis, showed that the SALL4-positive ICC cases had significantly more frequent lymph nodal metastasis (P = 0.0460), vascular invasion (P < 0.0001), and nerve invasion (P < 0.0001). Furthermore, the strong SALL4-positive cases (n = 7, 5 months) had shorter overall survival, when compared to moderate SALL4-positive (n = 46, 9 months) or SALL4-negative cases (n = 73, 7 months), respectively. Our data also suggest that SALL4 may be involved in the regulation of epithelial-mesenchymal transition (EMT) in ICC. Those results for the first time indicate an oncogenic role of SALL4 in ICC. Therefore, SALL4 may serve as a promising therapeutic target for ICC.