过氧化物酶体增殖物激活受体活性与肝癌切除术后患者的不良生存相关。

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

机构信息

Department of Surgical Gastroenterology and Transplantation, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

出版信息

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

DOI:10.1002/jhbp.745

PMID:32359017

Abstract

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.

摘要

背景/目的：目前已知的用于预测肝细胞癌（HCC）患者预后的临床有用生物标志物很少。本研究旨在通过 HCC 患者肝切除的 RNA 测序，研究 PPAR 活性与 ALDH7A1 表达之间的相关性及其预后意义。

方法

我们纳入了 2014 年 5 月至 2018 年 1 月期间在肝胆胰外科三级转诊中心接受 HCC 肝切除术的患者。通过 RNA 测序评估 PPAR 活性和 ALDH7A1 表达，并将其与总生存率、复发率和组织学特征相关联。

结果

我们纳入了 52 例患者，中位随访时间为 20.9 个月，主要为男性（88.5%），非肝硬化肝脏中单个肿瘤（84.6%）。具有特定 PPAR 靶基因表达谱（癌症簇 3）的患者 3 年总生存率为 48.6%，而对照组为 81.7%（P=.04，Log-rank 检验）。在校正年龄、肝硬化、微血管侵犯、肿瘤数量和无瘤切缘后，这一结果仍然显著（优势比 14.02，95%置信区间 1.92-102.22，P=.009）。ALDH7A1 表达与 PPAR 或任何结果均无相关性。