Department of Parasitology, Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
World J Gastroenterol. 2013 Apr 28;19(16):2456-65. doi: 10.3748/wjg.v19.i16.2456.
To evaluate a new immunohistological marker, annexin A1 (ANXA1), in cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC).
Expression of ANXA1 protein was investigated in liver tissues from patients with CCA and HCC by immunohistochemistry. Its expression on differences stages of tumor development was investigated in hamster CCA tissues induced by Opisthorchis viverrini and N-nitrosodimethylamine. Moreover, mRNA expression of ANXA1 was assessed in CCA cell lines by quantitative real-time polymerase chain reaction and silencing of ANXA1 gene expression using small interfering RNA.
In human CCA tissue arrays, immunohistochemical analysis revealed that the positive expression of ANXA1 was 94.1% (64/68 cases) consisting of a high expression (66.2%, 45/68 cases) and a low expression (33.8%, 23/68 cases). However, expression of ANXA1 protein was negative in all histologic patterns for HCC (46/46 cases) and healthy individuals (6/6 cases). In hamster with opisthorchiasis-associated CCA, the expression of ANXA1 was observed in the cytoplasm of inflammatory cells, bile duct epithelia and tumor cells. Grading scores of ANXA1 expression were significantly increased with tumor progression. In addition, mRNA expression of ANXA1 significantly increased in all of the various CCA cell lines tested compared to an immortalized human cholangiocyte cell line (MMNK1). Suppressing the ANXA1 gene significantly reduced the matrix metalloproteinase (MMP) 2 and MMP9, and transforming growth factor-β genes, but increased nuclear factor-κB gene expression.
ANXA1 is highly expressed in CCA, but low in HCC, suggesting it may serve as a new immunohistochemical marker of CCA. ANXA1 may play a role in opisthorchiasis-associated cholangiocarcinogenesis.
评估一种新的免疫组织化学标志物——膜联蛋白 A1（ANXA1）在胆管癌（CCA）和肝细胞癌（HCC）中的表达。
采用免疫组织化学方法检测 ANXA1 蛋白在 CCA 和 HCC 患者肝组织中的表达。通过仓鼠胆管癌组织诱导的华支睾吸虫和 N-亚硝二甲胺，研究其在肿瘤发展不同阶段的表达差异。此外，通过定量实时聚合酶链反应评估 CCA 细胞系中 ANXA1 的 mRNA 表达，并使用小干扰 RNA 沉默 ANXA1 基因表达。
在人类 CCA 组织芯片中，免疫组织化学分析显示 ANXA1 的阳性表达率为 94.1%（64/68 例），包括高表达（66.2%，45/68 例）和低表达（33.8%，23/68 例）。然而，在所有 HCC 组织学类型（46/46 例）和健康个体（6/6 例）中均未检测到 ANXA1 蛋白的表达。在华支睾吸虫相关的仓鼠 CCA 中，ANXA1 的表达可见于炎症细胞、胆管上皮细胞和肿瘤细胞的细胞质中。随着肿瘤的进展，ANXA1 表达的分级评分显著增加。此外，与永生化人胆管细胞系（MMNK1）相比，所有检测的各种 CCA 细胞系中 ANXA1 的 mRNA 表达均显著增加。抑制 ANXA1 基因显著降低了基质金属蛋白酶（MMP）2 和 MMP9，以及转化生长因子-β基因的表达，但增加了核因子-κB 基因的表达。
ANXA1 在 CCA 中高度表达，而在 HCC 中低表达，提示其可能成为 CCA 的一种新的免疫组织化学标志物。ANXA1 可能在华支睾吸虫相关的胆管癌发生中发挥作用。
