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醛酮还原酶1-A1在肝门部胆管癌中的表达及临床意义
詹榆1,俞文隆2,于观贞3,李文峰1*
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(1. 温州医科大学附属第一医院放化疗科, 温州 325000;
2. 海军军医大学(第二军医大学)东方肝胆外科医院肝胆二科, 上海 200438;
3. 上海中医药大学附属龙华医院肿瘤科, 上海 200032
*通信作者)
摘要:
目的 探讨醛酮还原酶1-A1(AKR1A1)在肝门部胆管癌组织中的表达及临床意义。方法 应用免疫组织化学法检测手术切除的49例肝门部胆管癌及癌旁组织(距离癌组织边缘至少2 cm)中的AKR1A1表达水平,采用χ2检验分析二者AKR1A1表达水平的相关性及与患者临床病理特征的关系。结果 肝门部胆管癌组织的A1KR1A1高表达率为59.2%(29/49),高于癌旁组织(25.0%,3/12),差异有统计学意义(P<0.05);AKR1A1在肝门部胆管癌组织中的表达与肿瘤大小和淋巴结转移有关(P=0.028、0.001)。Kaplan-Meier生存分析显示,AKR1A1高表达患者的总生存期中位数为15个月,短于低表达者(39个月,P=0.012);AKR1A1高表达患者的无进展生存期中位数为15个月,短于低表达者(32个月,P=0.022)。多因素分析结果提示浸润深度是肝门部胆管癌患者总生存期和无进展生存期的独立预测因素[比值比(OR)为0.174,95%置信区间(CI):0.041~0.741,P=0.018;OR为0.083,95% CI:0.011~0.618,P=0.015]。结论 AKR1A1参与肝门部胆管癌的进展和转移,有望成为预测胆管癌患者复发和预后的潜在生物学分子标志物。
关键词:  醛酮还原酶1-A1  肝门部胆管癌  免疫组织化学  预后
DOI:10.16781/j.0258-879x.2019.12.1384
投稿时间:2019-02-04修订日期:2019-07-01
基金项目:国家自然科学基金(81572856).
Expression and clinical significance of aldo-keto reductase 1-A1 in hilar cholangiocarcinoma
ZHAN Yu1,YU Wen-long2,YU Guan-zhen3,LI Wen-feng1*
(1. Department of Radiotherapy and Chemotherapy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China;
2. Department of Hepatobiliary (Ⅱ), Eastern Hepatobiliary Surgery Hospital, Naval Medical University (Second Military Medical University), Shanghai 200438, China;
3. Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
*Corresponding author)
Abstract:
Objective To explore the expression and clinical significance of aldo-keto reductase 1-A1 (AKR1A1) in hilar cholangiocarcinoma tissues. Methods Immunohistochemical assay was used to detect the expression of AKR1A1 in 49 hilar cholangiocarcinoma and adjacent normal tissues (at least 2 cm from the edge of the tumor). The correlation between the AKR1A1 expression and clinical variables of hilar cholangiocarcinoma patients was analyzed by χ2 test. Results The high-expression rate of AKR1A1 in cancer tissues was 59.2% (29/49), which was significantly higher than that in matched adjacent normal tissues (25.0%[3/12], P<0.05). We also noticed that the high-expression of AKR1A1 in hilar cholangiocarcinoma patients tissues was associated with tumor size (P=0.028) and lymph node metastasis (P=0.001). Survival analysis showed that the overall survival (median 15 months vs 39 months, P=0.012) and progression free survival (median 15 months vs 32 months, P=0.022) of AKR1A1-high-expression patients were significantly shorter compared with the low-expression patients. Multivariate analysis showed that the depth of invasion was associated with overall survival (odds ratio[OR] 0.174, 95% confidence interval[CI] 0.041-0.741, P=0.018) and progression free survival (OR 0.083, 95% CI 0.011-0.618, P=0.015). Conclusion AKR1A1 is involved in the progression and metastasis of hilar cholangiocarcinoma, suggesting that it might be a potential biomarker for predicting tumor recurrence and prognosis of patients with hilar cholangiocarcinoma.
Key words:  aldo-keto redutase 1-A1  hilar cholangiocarcinoma  immunohistochemistry  prognosis