Reduced N-cadherin expression is associated with metastatic potential and poor surgical outcomes of hepatocellular carcinoma

Authors

  • Da-qian Zhan,

    1. Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    Search for more papers by this author
    • Equally contributing to this work.

  • Shuang Wei,

    1. Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    Search for more papers by this author
    • Equally contributing to this work.

  • Cong Liu,

    1. Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    Search for more papers by this author
  • Bin-yong Liang,

    1. Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    Search for more papers by this author
  • Gui-bao Ji,

    1. Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    Search for more papers by this author
  • Xiao-ping Chen,

    1. Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    Search for more papers by this author
  • Min Xiong,

    1. Department of Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    Search for more papers by this author
  • Zhi-yong Huang

    Corresponding author
    1. Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    Search for more papers by this author

Dr Zhi-yong Huang, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, no. 1095, Jie Fang Da Dao, Wuhan 430030, China. Email: zyhuang@medmail.com.cn

Abstract

Background and Aim:  N-cadherin (N-cad), one of the classic cadherins, has been reported to be involved in tumor metastasis in some types of tumors. This study aims to investigate the expression status of N-cad in hepatocellular carcinoma (HCC) and the correlation between N-cad expression and metastatic potential, as well as the surgical outcomes of HCC.

Methods:  N-cad expression in HCC and adjacent liver tissues, as well as normal liver tissues, was studied by immunohistochemistry and Western blot, and the relationship between N-cad expression and the clinicopathological features of HCC was evaluated. By using RNA interference technique, the correlation of N-cad expression and metastatic potential was investigated by downregulating N-cad expression in HCCLM3 cells, and the effects of N-cad downregulation on cell aggregation, migration, and invasion were then analyzed. Furthermore, the correlation between N-cad expression and the surgical outcomes of a cohort of HCC patients was analyzed.

Results:  In liver tissues, N-cad was strongly expressed on cell–cell boundaries, whereas various reduced-expression patterns were observed in tumors. Of 64 HCC, 34 (53%) tumors showed reduced N-cad expression, compared with their adjacent liver tissues. The decreased expression of N-cad was significantly correlated with poorer tumor differentiation (P = 0.001) and vascular invasion (P = 0.003). N-cad knockdown in HCCLM3 cells resulted in decreased cell aggregation and increased cell migration and invasion. The decreased expression of N-cad in HCC was significantly associated with shorter postoperative disease-free survival (P = 0.039).

Conclusions:  N-cad expression is decreased in HCC, and the downregulation of N-cad is associated with the metastatic potential of HCC and poorer surgical prognosis.

Ancillary