SPARCL1 is a novel predictor of tumor recurrence and survival in hilar cholangiocarcinoma
SPARCL1 is a novel predictor of tumor recurrence and survival in hilar cholangiocarcinoma
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DOI：
10.1007/s13277-015-4206-4
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发表时间：
2016-03-01
期刊：
影响因子：
--
通讯作者：
Li, Zhaoshen
中科院分区：
文献类型：
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作者：
Yu, Yang;Chen, Yan;Li, Zhaoshen
富含半胱氨酸类蛋白的酸性分泌型蛋白1(SPARCL1)与多种肿瘤的发生、形成和发展密切相关，但其在肝门部胆管细胞癌中的作用尚不清楚。本研究应用免疫组织化学方法(IHC)检测了92例肝门部胆管癌组织芯片中SPARCL1蛋白的表达。体外实验检测SPARCL1过表达对细胞生长和迁移的影响。92例原发肿瘤中有46例(50.0%)SPARCL1表达缺失。SPARCL1的表达与低分化或未分化癌呈负相关(P=0.030)，与淋巴结转移呈负相关(P=0.047)。生存分析表明，SPARCL1是预测肝门部胆管癌患者预后的独立因素。SPARCL1过表达通过抑制基质金属蛋白酶-9、基质金属蛋白酶-2、波形蛋白和纤维连接蛋白的表达抑制肿瘤细胞的体外迁移，而不抑制体外细胞的增殖。我们的结果提示，SPARCL1基因缺失与肝门部胆管细胞癌的发生有关，可作为判断患者预后的一种新的分子生物标志物。
Secreted protein acidic and rich in cysteines-like protein 1 (SPARCL1) has been implicated in tumor initiation, formation, and progression of various cancers, yet its role in hilar cholangiocarcinoma remains largely uncharacterized. In the present study, tissue microarrays containing resected hilar cholangiocarcinoma specimens from 92 patients were used to evaluate the expression of SPARCL1 protein by immunohistochemistry (IHC). In vitro assays were used to determine the effect of SPARCL1 overexpression on cell growth and migration. Loss of SPARCL1 expression was observed in 46 (50.0 %) of the 92 primary tumors. SPARCL1 expression is inversely associated with poorly or undifferentiation specimens (P = 0.030) in addition to lymph node metastasis (P = 0.047). Survival analysis demonstrated that SPARCL1 is an independent factor in predicting the outcome of patients with hilar cholangiocarcinoma. SPARCL1 overexpression suppressed tumor cell migration in vitro by inhibiting MMP-9, MMP-2, Vimentin, and Fibronectin expression, whereas did not inhibit cell proliferation in vitro. Our results suggest that loss of SPARCL1 is involved in the tumorigenesis of hilar cholangiocarcinoma and may serve as a novel molecular biomarker for patients' outcome.