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HDAC8 表达降低提示肝内胆管细胞癌患者预后不良。

Decreased expression of HDAC8 indicates poor prognosis in patients with intrahepatic cholangiocarcinoma.

机构信息

Laboratory of Pathology, West China Hospital, Sichuan University, 37 Guoxue Road, Chengdu 610041, China; Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, Chengdu 610041, China.

Laboratory of Pathology, West China Hospital, Sichuan University, 37 Guoxue Road, Chengdu 610041, China.

出版信息

Hepatobiliary Pancreat Dis Int. 2019 Oct;18(5):464-470. doi: 10.1016/j.hbpd.2019.07.006. Epub 2019 Jul 24.

Abstract

BACKGROUND

Intrahepatic cholangiocarcinoma (ICC) is a highly malignant primary tumor in the liver, and the rates of incidence and mortality are rapidly increasing globally. Histone deacetylase 8 (HDAC8) is a transcriptional regulator and is associated with tumorigenesis of several tumor types. This study aimed to evaluate the correlation between HDAC8 expression and clinicopathological parameters in ICC patients.

METHODS

ICC tissues and corresponding nonmalignant bile duct tissues were obtained from 60 patients. HDAC8 and Ki-67 expression were evaluated by immunohistochemistry staining. HDAC8 expression and the clinicopathological features and prognosis of the patients were analyzed. The mRNA level of HDAC8 in ICC was further analyzed using data from The Cancer Genome Atlas (TCGA).

RESULTS

The expression of HDAC8 were lower in ICC tissues (39/60, 65%) than in the corresponding nonmalignant bile duct tissues (54/60, 90%) (P = 0.001). Low HDAC8 expression in ICC was significantly associated with lymph node metastases (47.6% vs. 17.9%, P = 0.015). In addition, the positive cells rate of HDAC8 was statistically and negatively correlated with the Ki-67 index in ICC lesions (r = -0.7660, P < 0.001). Importantly, the overall survival rate and recurrence-free survival rate in ICC patients with low HDAC8 expression were lower than those with high HDAC8 expression (P = 0.008 and P = 0.011, respectively).

CONCLUSIONS

Decreased HDAC8 expression in ICC is related to poor prognosis, and HDAC8 may be an independent prognostic indicator of ICC patients after curative resection.

摘要

背景

肝内胆管癌(ICC)是一种高度恶性的肝脏原发性肿瘤,其发病率和死亡率在全球范围内迅速上升。组蛋白去乙酰化酶 8(HDAC8)是一种转录调节剂,与多种肿瘤类型的肿瘤发生有关。本研究旨在评估 HDAC8 表达与 ICC 患者临床病理参数之间的相关性。

方法

收集 60 例 ICC 患者的肿瘤组织及相应的非恶性胆管组织。采用免疫组织化学染色法检测 HDAC8 和 Ki-67 的表达。分析 HDAC8 表达与患者临床病理特征及预后的关系。进一步采用癌症基因组图谱(TCGA)的数据分析 ICC 中 HDAC8 的 mRNA 水平。

结果

HDAC8 在 ICC 组织中的表达(39/60,65%)明显低于相应的非恶性胆管组织(54/60,90%)(P=0.001)。ICC 中 HDAC8 低表达与淋巴结转移显著相关(47.6%比 17.9%,P=0.015)。此外,HDAC8 的阳性细胞率与 ICC 病变中的 Ki-67 指数呈统计学负相关(r=-0.7660,P<0.001)。重要的是,HDAC8 低表达的 ICC 患者的总生存率和无复发生存率均低于 HDAC8 高表达的患者(P=0.008 和 P=0.011)。

结论

ICC 中 HDAC8 表达降低与预后不良相关,HDAC8 可能是 ICC 患者根治性切除术后的独立预后指标。

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