Abstract

BackgroundAutophagy-related proteins may predict postresection overall survival (OS) and disease-free survival (DFS) in patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC).MethodsWe 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.ResultsWe 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.ConclusionHigh LC3 expression in tumors is significantly associated with mild clinicopathological characteristics and favorable clinical prognosis in patients with cHCC-CC after resection.

Highlights

  • Autophagy-related proteins may predict postresection overall survival (OS) and disease-free survival (DFS) in patients with combined hepatocellular carcinoma and cholangiocarcinoma

  • This few form of liver cancer is clinically quiescent until the advanced stages, which often manifest with abdominal pain, jaundice, hepatomegaly, and weight loss [3]. Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is an extremely aggressive liver cancer that is often associated with poor long-term prognosis [1, 2]

  • We previously reported that high intratumoral LC3 expression and the liver microenvironment is associated with mild clinicopathological features in patients with hepatocellular carcinoma (HCC) [7, 8]

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Summary

Introduction

Autophagy-related proteins may predict postresection overall survival (OS) and disease-free survival (DFS) in patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC). In type A, HCC and CC are showed at different sites of the liver [3]; in type B, HCC and CC are showed at adjacent sites [3]; and in type C, HCC and CC are combined within the same tumor [3] This few form of liver cancer is clinically quiescent until the advanced stages, which often manifest with abdominal pain, jaundice, hepatomegaly, and weight loss [3]. CHCC-CC is an extremely aggressive liver cancer that is often associated with poor long-term prognosis [1, 2] This is largely due to its misdiagnosis as either HCC or CC pre-operatively [4]. Identification of predictive biomarkers for cHCC-CC overall survival (OS) and disease-free survival (DFS) can help promote the clinical prognosis of patients with cHCC-CC undergoing surgical resection

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