Oncotarget

Research Papers:

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

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

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Oncotarget. 2017; 8:91902-91913. https://doi.org/10.18632/oncotarget.19763

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Abstract

Chih-Wen Lin1,2,3,4, Chih-Che Lin6, Po-Huang Lee4,5, Gin-Ho Lo2,4, Pei-Min Hsieh5, Kah Wee Koh2,3, Chih-Yuan Lee7, Yao-Li Chen8, Chia-Yen Dai9, Jee-Fu Huang9, Wang-Long Chuang9, Yaw-Sen Chen4,5,* and Ming-Lung Yu9,10,11,*

1Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan

2Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan

3Health Examination Center, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan

4School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan

5Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan

6Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

7Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan

8Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan

9Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan

10Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan

11Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

*These authors have contributed equally to this work

Correspondence to:

Ming-Lung Yu, email: [email protected]

Keywords: albumin, autophagy, liver failure, post-hepatectomy immediate mortality, predictor

Received: May 19, 2017     Accepted: June 30, 2017     Published: August 01, 2017

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.


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