Format

Send to

Choose Destination
Cell Death Dis. 2018 Feb 15;9(3):264. doi: 10.1038/s41419-018-0308-4.

Predictive and preventive significance of AMPK activation on hepatocarcinogenesis in patients with liver cirrhosis.

Author information

1
Chongqing Key Laboratory of Hepatobiliary Surgery and Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People's Republic of China.
2
Department of Gastroenterology, the Fifth People's Hospital of Chengdu, Chengdu, Sichuan, 611130, People's Republic of China.
3
Chongqing Key Laboratory of Hepatobiliary Surgery and Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People's Republic of China. gongjianping11@126.com.

Abstract

Metformin has been demonstrated to prevent hepatocellular carcinoma (HCC). Metformin acts mainly by phosphorylation of AMPK. However, the phosphorylation status of AMPK and its role in the prediction and prevention of HCC in cirrhotic patients remains unclear. The phosphorylation status of AMPK (Thr172) was determined by immunostaining in tissue microarrays of 426 cirrhotic liver tissues. Low expression of p-AMPK was observed in 94 (22.1%) cases. The median follow-up time was 87 months. HCC occurrence probability at 1/3/5/10 years after Hassab procedure was 3.1/9.6/13.8/30.6% in patients with p-AMPK low expression and 0/0.3/0.3/8% in patients with p-AMPK high expression, respectively. HCC occurrence risk was significantly higher in patients with p-AMPK low expression in univariable analysis (HR, 6.25; 95% CI: 3.36-11.60; P < 0.001) and multivariable analysis (HR, 6.0; 95% CI: 3.24-11.10; P < 0.001). An independent external cohort validated the significance of p-AMPK low expression. In addition, in vivo experiments demonstrated that AMPK activation status was negatively related to HCC occurrence and blocking autophagy by chloroquine counteracted the protective effect of AMPK phosphorylation. These results present novel insight into a critical predictive role of AMPK activation in hepatocarcinogenesis and AMPK activation seems to be a potential target for the prevention of hepatocellular carcinoma in patients with liver cirrhosis.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center