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.

Next-generation sequencing of endoscopic ultrasound guided microbiopsies from pancreatic cystic neoplasms.

AIMS: Interpretation of cytology samples from pancreatic cysts is challenging. A novel microbiopsy forceps used during endoscopic ultrasound examinations offers new opportunities for histological examination of tissue from pancreatic cysts as well as next-generation sequencing. The aim of this study was to analyse the results of next-generation sequencing of microbiopsies from pancreatic cysts. METHODS AND RESULTS: Microbiopsies from 27 patients were obtained, 23 of which were subjected to next-generation sequencing. Sixteen intraductal papillary mucinous neoplasms harboured mutations in genes regulating cell cycle and repair, and three were without mutations. Most frequent mutations were found in the KRAS and GNAS genes, and these were often concomitant. Three serous cystic neoplasms were without mutations, while with regard to histology, a non-diagnostic microbiopsy harboured a KRAS and a TP53 mutation and was deemed malignant after clinical follow-up. Three patients underwent surgery, and the point mutations detected in the microbiopsies were confirmed in the resected specimens. We identified one resected sample with an additional GNAS mutation which was not identified in the microbiopsy. CONCLUSIONS: Next-generation sequencing of microbiopsies may have the potential to improve diagnostic decision-making.