Peroxisome proliferator-activated receptor activity correlates with poor survival in patients resected for hepatocellular carcinoma

J Hepatobiliary Pancreat Sci. 2021 Apr;28(4):327-335. doi: 10.1002/jhbp.745. Epub 2020 Jun 17.


Background/purpose: Few clinically useful biomarkers are known to predict prognosis in patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate the correlation between PPAR activity and ALDH7A1 expression and their prognostic significance using RNA sequencing in patients undergoing liver resection for HCC.

Methods: We included patients undergoing liver resection for HCC at a tertiary referral center for hepato-pancreato-biliary surgery between May 2014 and January 2018. PPAR activity and ALDH7A1 expression were evaluated by RNA sequencing and correlated with overall survival, recurrence and histological features.

Results: We included 52 patients with a median follow-up of 20.9 months, predominantly males (88.5%) with a single tumor (84.6%) in a non-cirrhotic liver (73.1%). Three-year overall survival was 48.6% in patients with a specific PPAR target gene expression profile (cancer cluster 3) compared with 81.7% in controls (P = .04, Log-rank test). This remained significant (odds ratio 14.02, 95% confidence interval 1.92-102.22, P = .009) when adjusted for age, cirrhosis, microvascular invasion, number of tumors and free resection margins. ALDH7A1 expression was not correlated with PPAR or any outcomes.

Conclusion: PPAR activity in a subset of tumor samples was associated with reduced overall survival indicating that PPAR may be a valuable prognostic biomarker.

MeSH terms

  • Carcinoma, Hepatocellular* / surgery
  • Disease-Free Survival
  • Female
  • Hepatectomy
  • Humans
  • Liver Neoplasms* / surgery
  • Male
  • Neoplasm Recurrence, Local / surgery
  • Peroxisome Proliferator-Activated Receptors* / genetics
  • Prognosis
  • Retrospective Studies


  • Peroxisome Proliferator-Activated Receptors