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

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Tumor Biology

Abstract

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 = 0.008), lymph node metastasis (P < 0.001), and Beclin-1 expression level (P < 0.001). 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 = 0.026). And high LC3B expression tended to be related with shorter progression-free survival (PFS) (P = 0.074), 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 = 0.047) and LC3B expression level (P = 0.047) 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.

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Abbreviations

HCC:

Hepatocellular carcinoma

OS:

Overall survival

IHC:

Immunohistochemistry

LC3B:

Microtubule-associated protein light chains 3B

Beclin-1:

Associated autophagy-related key regulator

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 81372374), the Combination Project of Production, Education and Research from Guangdong Province and Ministry of Education (No. 2012B091100460), and the Science and Technology Planning Project of Guangdong Province 2011B031800076 (to Q. Lin), 2011B031800014 (to M. Dong), and 2012B031800259 (to J. Wen).

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Authors and Affiliations

  1. Department of Medical Oncology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

    Dong-Hao Wu, Jie Chen, Ze-Xiao Lin, Dan-Yun Ruan, Xing Li, Qu Lin,  Min-Dong, Xiao-Kun Ma, Zhan-Hong Chen, Xiang-Yuan Wu & Jing-Yun Wen

  2. Guangdong Provincial Key Laboratory of Liver Disease Research, Sun Yat-sen University, Guangzhou, China

    Chang-Chang Jia

  3. Cell-gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

    Chang-Chang Jia

  4. Department of Radiation Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

    Xiang-Bo Wan

  5. Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

    Min-Dong & Na Cheng

  6. Department of Nephrology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China

    Yan-Fang Xing

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  1. Dong-Hao Wu
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Corresponding authors

Correspondence to Xiang-Yuan Wu or Jing-Yun Wen.

Additional information

Dong-Hao Wu and Chang-Chang Jia contributed equally to this work.

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Wu, DH., Jia, CC., Chen, J. et al. Autophagic LC3B overexpression correlates with malignant progression and predicts a poor prognosis in hepatocellular carcinoma. Tumor Biol. 35, 12225–12233 (2014). https://doi.org/10.1007/s13277-014-2531-7

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  • DOI: https://doi.org/10.1007/s13277-014-2531-7

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