Low expression of ARID1A correlates with poor prognosis in intrahepatic cholangiocarcinoma

World J Gastroenterol. 2016 Jul 7;22(25):5814-21. doi: 10.3748/wjg.v22.i25.5814.

Abstract

Aim: To investigate the relationship between ARID1A expression and clinicopathologic parameters, as well as its prognostic value, for patients with intrahepatic cholangiocarcinoma (IHCC).

Methods: We assessed ARID1A protein and mRNA expression in IHCC tissues and paracarcinomatous (PC) tissues from 57 patients with IHCC using western blot and quantitative real-time reverse transcription polymerase chain reaction, respectively. We used Fisher's exact and χ(2) tests to analyze relationships between clinicopathological parameters and ARID1A expression. The Kaplan-Meier method and Cox regression were used to analyze survival.

Results: The mean ARID1A protein level in IHCC tissues was 1.16 ± 0.36 relative units (RU), which was significantly lower than that in PC tissues (1.26 ± 0.21 RU, P < 0.01) and NL tissues (1.11 ± 0.31, P < 0.001). The mean ARID1A mRNA level in IHCC tissues (1.20 ± 0.18) was also lower than that in PC tissues (1.27 ± 0.15, P < 0.001) and normal liver tissues (1.15 ± 0.34, P < 0.001). Low ARID1A expression was significantly associated with tumor nodules, vein invasion, and recurrence. Median overall survival (OS) and disease-free survival (DFS) for the low ARID1A expression group was 15.0 and 7.0 mo, respectively, which were significantly shorter than those for the high ARID1A expression group at 25.0 and 22.0 mo (OS: P < 0.01; DFS: P < 0.001), respectively. Low ARID1A expression was significantly associated with worse OS (HR = 3.967, 95%CI: 1.299-12.118, P = 0.016) in multivariate analyses.

Conclusion: Low expression of ARID1A is associated with poor prognosis in patients with IHCC, and thus may be a potential prognostic biomarker candidate in IHCC.

Keywords: ARID1A; Biomarker; Intrahepatic cholangiocarcinoma; Prognosis; Progression.

MeSH terms

  • Bile Duct Neoplasms / genetics*
  • Bile Duct Neoplasms / metabolism
  • Bile Duct Neoplasms / mortality
  • Bile Ducts, Intrahepatic*
  • Blotting, Western
  • Case-Control Studies
  • Cholangiocarcinoma / genetics*
  • Cholangiocarcinoma / metabolism
  • Cholangiocarcinoma / mortality
  • DNA-Binding Proteins
  • Disease-Free Survival
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / mortality
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Prognosis
  • Proportional Hazards Models
  • RNA, Messenger / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • ARID1A protein, human
  • DNA-Binding Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • Transcription Factors