Autophagic LC3B overexpression correlates with malignant progression and predicts a poor prognosis in hepatocellular carcinoma

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• 作者：Dong-Hao Wu ; Chang-Chang Jia ; Jie Chen ; Ze-Xiao Lin ; Dan-Yun Ruan ; Xing Li…
• 关键词：Hepatocellular carcinoma ; LC3B ; Beclin ; 1 ; Vascular invasion ; Lymph node metastasis ; Prognostic biomarker
• 刊名：Tumor Biology
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：35
• 期：12
• 页码：12225-12233
• 全文大小：1,624 KB
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• 作者单位：Dong-Hao Wu (1)
  Chang-Chang Jia (2) (3)
  Jie Chen (1)
  Ze-Xiao Lin (1)
  Dan-Yun Ruan (1)
  Xing Li (1)
  Qu Lin (1)
  Min-Dong (1) (5)
  Xiao-Kun Ma (1)
  Xiang-Bo Wan (4)
  Na Cheng (5)
  Zhan-Hong Chen (1)
  Yan-Fang Xing (6)
  Xiang-Yuan Wu (1)
  Jing-Yun Wen (1)
  
  1. Department of Medical Oncology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
  2. Guangdong Provincial Key Laboratory of Liver Disease Research, Sun Yat-sen University, Guangzhou, China
  3. Cell-gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
  5. Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
  4. Department of Radiation Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
  6. Department of Nephrology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
  
• 刊物主题：Cancer Research;
• 出版者：Springer Netherlands
• ISSN：1423-0380

文摘

Autophagy is a process that involves lysosomal degradations of cellular organelles and closely related to tumor occurrence and progression. However, its importance in hepatocellular carcinoma (HCC) was still controversial. Therefore, this study is aimed to address the clinicopathologic effect of microtubule-associated protein 1 light chain 3B (LC3B) and Beclin-1, as autophagic markers, in HCC patients. Tissue microarray-based immunohistochemistry was used to examine the expression of LC3B and another autophagy key regulator (Beclin-1) in 156 operable HCC patients. Kaplan-Meier analysis, chi-square test, and Spearman’s correlation analysis were used to analyze correlation of LC3B and Beclin-1 and their influence on clinical characteristics and prognosis. We found that the expression level of LC3B was significantly associated with vascular invasion (P--.008), lymph node metastasis (P--.001), and Beclin-1 expression level (P--.001). However, LC3B was not related to other clinicopathological features, including hepatitis B virus infection, liver cirrhosis, tumor number, tumor size, pathology grade, and tumor-node-metastasis (TNM) stage. Besides, correlation between the expression of Beclin-1 and clinicopathological features were not identified. Survival analysis showed that patients with high LC3B expression had a poorer 5-year overall survival (OS) rate than those with low LC3B expression (high vs. low: 79.5?% vs. 20.5?%, P--.026). And high LC3B expression tended to be related with shorter progression-free survival (PFS) (P--.074), whereas the expression level of Beclin-1 did not show statistically significant association with OS or PFS. Further multivariate analysis revealed that lymph node metastasis (P--.047) and LC3B expression level (P--.047) were independent factors to predict the prognosis of OS in all patients. Our study demonstrated that high expression of LC3B, correlated with vascular invasion and lymph node metastasis, might be a novel prognostic biomarker and would be a potential therapy target for HCC, especially in operable patients.