Role of autophagy-related protein in the prognosis of combined hepatocellular carcinoma and cholangiocarcinoma after surgical resection

Daw Shyong Perng, Chao Ming Hung, Hung Yu Lin, Paul Morgan, Yao Chun Hsu, Tsung Chin Wu, Pei Min Hsieh, Jen Hao Yeh, Pojen Hsiao, Chih Yuan Lee, Yu Chan Li, Ya Chin Wang, Yaw Sen Chen, Chih Wen Lin*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

6 Scopus citations


Background: Autophagy-related proteins may predict postresection overall survival (OS) and disease-free survival (DFS) in patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC). Methods: We prospectively investigated how these proteins affect clinical prognosis in 40 patients who underwent hepatectomy for cHCC-CC from 2011 to 2019 at a Taiwanese hospital. Levels of autophagy-related proteins, namely LC3, Beclin-1, and p62, were immunohistochemically assessed in patient tumor and non-tumor tissues. Results: We noted that LC3 expression was significantly correlated with mild clinicopathological characteristics, including macrovascular invasion, lymph node metastasis, American Joint Committee on Cancer and Barcelona Clinic Liver Cancer stages, recurrence, and mortality. Ten patient showed tumor recurrence, and 15 patients died. Postresection 5-year OS and DFS rates were 43.7 and 57.4%, respectively. Cox regression analysis showed that high intratumoral LC3 expression was significantly associated with improved OS [hazard ratio (HR; 95% confidence interval (CI)): (1.68–26.9), p = 0.007], but multiple tumors and microvascular invasion was significantly correlated with poor OS [HR (95% CI): 0.03 (0.01–0.34), p = 0.004, and 0.07 (0.01–0.46), p = 0.006, respectively]. Furthermore, high LC3 expression and cirrhosis had improved DFS [HR (95% CI): 51.3 (2.85–922), p = 0.008, and 17.9 (1.05–306), p = 0.046, respectively]. The 5-year OS and DFS rates were respectively 61.2 and 74.6% in high LC3 expression patients and 0 and 0% in those with low LC3 expression. Conclusion: High LC3 expression in tumors is significantly associated with mild clinicopathological characteristics and favorable clinical prognosis in patients with cHCC-CC after resection.

Original languageEnglish
Article number828
JournalBMC Cancer
Issue number1
StatePublished - 12 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2021, The Author(s).


  • Autophagy
  • Combined hepatocellular carcinoma and cholangiocarcinoma
  • LC3
  • Predictive factors
  • Prognosis


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