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

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. Highlight Pommergaard and colleagues investigated peroxisome proliferator‐activated receptor (PPAR) activity by RNA sequencing in hepatocellular carcinoma in patients undergoing liver resection. The PPAR target gene expression profile correlated with overall survival, showing a 3‐year survival rate of 49% versus 82%, even when corrected for confounders. PPAR may be a valuable prognostic biomarker.