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

被引:85
|
作者
Wu, Dong-Hao [1 ]
Jia, Chang-Chang [2 ,3 ]
Chen, Jie [1 ]
Lin, Ze-Xiao [1 ]
Ruan, Dan-Yun [1 ]
Li, Xing [1 ]
Lin, Qu [1 ]
Min-Dong [1 ,5 ]
Ma, Xiao-Kun [1 ]
Wan, Xiang-Bo [4 ]
Cheng, Na [5 ]
Chen, Zhan-Hong [1 ]
Xing, Yan-Fang [6 ]
Wu, Xiang-Yuan [1 ]
Wen, Jing-Yun [1 ]
机构
[1] Sun Yat Sen Univ, Affiliated Hosp 3, Dept Med Oncol, Guangzhou 510275, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Guangdong Prov Key Lab Liver Dis Res, Guangzhou 510275, Guangdong, Peoples R China
[3] Sun Yat Sen Univ, Affiliated Hosp 3, Cell Gene Therapy Translat Med Res Ctr, Guangzhou 510275, Guangdong, Peoples R China
[4] Sun Yat Sen Univ, Affiliated Hosp 6, Dept Radiat Oncol, Guangzhou 510275, Guangdong, Peoples R China
[5] Sun Yat Sen Univ, Affiliated Hosp 3, Dept Pathol, Guangzhou 510275, Guangdong, Peoples R China
[6] Guangzhou Med Univ, Affiliated Hosp 3, Dept Nephrol, Guangzhou, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
Hepatocellular carcinoma; LC3B; Beclin-1; Vascular invasion; Lymph node metastasis; Prognostic biomarker; NEGATIVE BREAST-CANCER; CELL-DEATH; BECLIN; EXPRESSION; ADENOCARCINOMA; ACTIVATION; DISEASE; TUMORS; YEAST;
D O I
10.1007/s13277-014-2531-7
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:12225 / 12233
页数:9
相关论文
共 50 条
  • [31] Overexpression of chaperonin containing TCP1, subunit 3 predicts poor prognosis in hepatocellular carcinoma
    Xiao Cui
    Zhi-Ping Hu
    Zhao Li
    Peng-Ji Gao
    Ji-Ye Zhu
    World Journal of Gastroenterology, 2015, 21 (28) : 8588 - 8604
  • [32] Overexpression of chaperonin containing TCP1, subunit 3 predicts poor prognosis in hepatocellular carcinoma
    Cui, Xiao
    Hu, Zhi-Ping
    Li, Zhao
    Gao, Peng-Ji
    Zhu, Ji-Ye
    WORLD JOURNAL OF GASTROENTEROLOGY, 2015, 21 (28) : 8588 - 8604
  • [33] NSUN5 promotes progression and predicts poor prognosis in hepatocellular carcinoma
    Zhang, Xiao-Wen
    Wu, Lu-Yi
    Liu, Hui-Rong
    Huang, Yan
    Qi, Qin
    Zhong, Rui
    Zhu, Lu
    Gao, Chun-Fang
    Zhou, Lin
    Yu, Jian
    Wu, Huan-Gan
    ONCOLOGY LETTERS, 2022, 24 (06)
  • [34] Upregulation of cystatin SN promotes hepatocellular carcinoma progression and predicts a poor prognosis
    Cui, Yifeng
    Sun, Dan
    Song, Ruipeng
    Zhang, Shugeng
    Liu, Xirui
    Wang, Yan
    Meng, Fanzheng
    Lan, Yaliang
    Han, Jihua
    Pan, Shangha
    Liang, Shuhang
    Zhang, Bo
    Guo, Hongrui
    Liu, Yufeng
    Lu, Zhaoyang
    Liu, Lianxin
    JOURNAL OF CELLULAR PHYSIOLOGY, 2019, 234 (12) : 22623 - 22634
  • [35] Overexpression of CASC19 contributes to tumor progression and predicts poor prognosis after radical resection in hepatocellular carcinoma
    Hou, Ying
    Tang, Yipeng
    Ma, Chi
    Yu, Jingbo
    Jia, Youpeng
    DIGESTIVE AND LIVER DISEASE, 2023, 55 (06) : 799 - 806
  • [36] The ubiquitin isopeptidase USP10 deubiquitinates LC3B to increase LC3B levels and autophagic activity
    Jia, Rui
    Bonifacino, Juan S.
    Journal of Biological Chemistry, 2021, 296
  • [37] Correlation of Altered Expression of the Autophagy Marker LC3B with Poor Prognosis in Astrocytoma
    Winardi, Daniel
    Tsai, Hung-Pei
    Chai, Chee-Yin
    Chung, Chia-Li
    Loh, Joon-Khim
    Chen, Yung-Hsiang
    Hsieh, Ching-Liang
    BIOMED RESEARCH INTERNATIONAL, 2014, 2014
  • [38] Neuron-glial antigen 2 overexpression in hepatocellular carcinoma predicts poor prognosis
    Lu, Le-Le
    Sun, Jing
    Lai, Jie-Juan
    Jiang, Yan
    Bai, Lian-Hua
    Zhang, Lei-Da
    WORLD JOURNAL OF GASTROENTEROLOGY, 2015, 21 (21) : 6649 - 6659
  • [39] Neuron-glial antigen 2 overexpression in hepatocellular carcinoma predicts poor prognosis
    Le-Le Lu
    Jing Sun
    Jie-Juan Lai
    Yan Jiang
    Lian-Hua Bai
    Lei-Da Zhang
    World Journal of Gastroenterology, 2015, (21) : 6649 - 6659
  • [40] The ubiquitin isopeptidase USP10 deubiquitinates LC3B to increase LC3B levels and autophagic activity
    Jia, Rui
    Bonifacino, Juan S.
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2021, 296