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自噬标志物LC3能强烈预测肝细胞癌手术切除后的近期死亡率。

The autophagy marker LC3 strongly predicts immediate mortality after surgical resection for hepatocellular carcinoma.

作者信息

Lin Chih-Wen, Lin Chih-Che, Lee Po-Huang, Lo Gin-Ho, Hsieh Pei-Min, Koh Kah Wee, Lee Chih-Yuan, Chen Yao-Li, Dai Chia-Yen, Huang Jee-Fu, Chuang Wang-Long, Chen Yaw-Sen, Yu Ming-Lung

机构信息

Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan.

Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.

出版信息

Oncotarget. 2017 Aug 1;8(54):91902-91913. doi: 10.18632/oncotarget.19763. eCollection 2017 Nov 3.

Abstract

The remnant liver's ability to regenerate may affect post-hepatectomy immediate mortality. The promotion of autophagy post-hepatectomy could enhance liver regeneration and reduce mortality. This study aimed to identify predictive factors of immediate mortality after surgical resection for hepatocellular carcinoma (HCC). A total of 535 consecutive HCC patients who had undergone their first surgical resection in Taiwan were enrolled between 2010 and 2014. Clinicopathological data and immediate mortality, defined as all cause-mortality within three months after surgery, were analyzed. The expression of autophagy proteins (LC3, Beclin-1, and p62) in adjacent non-tumor tissues was scored by immunohistochemical staining. Approximately 5% of patients had immediate mortality after surgery. The absence of LC3, hypoalbuminemia (<3.5 g/dl), high alanine aminotransferase, and major liver surgery were significantly associated with immediate mortality in univariate analyses. Multivariate logistic regression demonstrated that absence of LC3 (hazard ratio/95% confidence interval: 40.8/5.14-325) and hypoalbuminemia (2.88/1.11-7.52) were significantly associated with immediate mortality. The 3-month cumulative incidence of mortality was 12.1%, 13.0%, 21.4% and 0.4%, respectively, among patients with absence of LC3 expression, hypoalbuminemia, both, or neither of the two. In conclusion, the absence of LC3 expression in adjacent non-tumor tissues and hypoalbuminemia were strongly predictive of immediate mortality after resection for HCC.

摘要

残余肝脏的再生能力可能会影响肝切除术后的即刻死亡率。肝切除术后促进自噬可增强肝脏再生并降低死亡率。本研究旨在确定肝细胞癌(HCC)手术切除后即刻死亡率的预测因素。2010年至2014年间,台湾地区共有535例首次接受手术切除的连续性HCC患者入组。分析了临床病理数据以及定义为术后三个月内全因死亡率的即刻死亡率。通过免疫组织化学染色对相邻非肿瘤组织中自噬蛋白(LC3、Beclin-1和p62)的表达进行评分。约5%的患者术后出现即刻死亡。在单因素分析中,LC3缺失、低白蛋白血症(<3.5 g/dl)、高丙氨酸转氨酶以及大肝手术与即刻死亡率显著相关。多因素逻辑回归显示,LC3缺失(风险比/95%置信区间:40.8/5.14 - 325)和低白蛋白血症(2.88/1.11 - 7.52)与即刻死亡率显著相关。在LC3表达缺失、低白蛋白血症、两者皆有或两者皆无的患者中,3个月累积死亡率分别为12.1%、13.0%、21.4%和0.4%。总之,相邻非肿瘤组织中LC3表达缺失和低白蛋白血症是HCC切除术后即刻死亡率的强预测因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb6/5696150/8a58356026ee/oncotarget-08-91902-g001.jpg

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