High expression of XRCC5 is associated with metastasis through Wnt signaling pathway and predicts poor prognosis in patients with hepatocellular carcinoma

Eur Rev Med Pharmacol Sci. 2019 Sep;23(18):7835-7847. doi: 10.26355/eurrev_201909_18993.

Abstract

Objective: Metastasis is one of the main causes of leading recurrence and death in patients with hepatocellular carcinoma (HCC). XRCC5 can affect several types of human cancers. The aim of the present study is to explore the metastasis correlation between the expression level of XRCC5 protein in HCC cell lines with different metastatic potentials and the prognosis of patients with HCC.

Materials and methods: Hepatocellular carcinoma cell lines used in this study include MHCC97-H, MHCC97-L, HepG2, and HL-7702.

Results: XRCC5 was widely expressed in HCC cell lines analyzed by Real-Time Reverse Transcription PCR and Western blotting. The levels of XRCC5 protein and mRNA were positively correlated with the migration and invasion capability of HCC cell lines. SiRNA-XRCC5 significantly suppressed the migration and invasion of HCC cells. Immunohistochemistry (IHC) results showed that high-expressed XRCC5 in patients with HCC was associated with advanced tumors, size, and microvascular invasion and lower overall survival time than the low-expressed. The expression levels of CTNNB1 and MMP9 decreased by knocked down XRCC5 which may promote the progression of HCC via the Wnt/β-catenin signaling pathway.

Conclusions: Our results suggest that the high expression of XRCC5 predicts poor prognosis in patients with HCC, and XRCC5 may be a potential biomarker to inhibit the invasion and migration of HCC.

MeSH terms

  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / mortality
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Movement
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Ku Autoantigen / genetics*
  • Ku Autoantigen / pharmacology
  • Liver Neoplasms / pathology
  • Liver Neoplasms / secondary*
  • Male
  • Matrix Metalloproteinase 9 / drug effects
  • Matrix Metalloproteinase 9 / metabolism
  • Microvessels / pathology
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Metastasis / genetics
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Staging / methods
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Messenger / pharmacology
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / pharmacology
  • Wnt Signaling Pathway / genetics*
  • beta Catenin / drug effects
  • beta Catenin / metabolism

Substances

  • CTNNB1 protein, human
  • RNA, Messenger
  • RNA, Small Interfering
  • beta Catenin
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • XRCC5 protein, human
  • Ku Autoantigen