Department of Surgery and Transplantation, Rigshospitalet, Copenhagen University Hospital, Department of Clinical Medicine, Inge Lehmannsvej 7, 2100, Copenhagen, Denmark.
Department of Surgery and Transplantation, Rigshospitalet, Copenhagen University Hospital, Department of Clinical Medicine, Inge Lehmannsvej 7, 2100, Copenhagen, Denmark.
Surg Oncol. 2022 Mar;40:101677. doi: 10.1016/j.suronc.2021.101677. Epub 2021 Nov 23.
Several members of the aldehyde dehydrogenase (ALDH) isoenzyme family have been suggested as prognostic biomarkers in patients with hepatocellular carcinoma (HCC). The aim of the study was to evaluate overall ALDH family member expression by RNA sequencing and hierarchical clustering in tumor and adjacent liver tissue to predict survival and evaluate correlation with liver cirrhosis in patients undergoing liver resection for HCC.
We included patients having undergone liver resection for HCC between May 2014 and January 2018 at a tertiary referral university hospital (Copenhagen University Hospital, Rigshospitalet, Denmark). ALDH family member expression was evaluated by RNA sequencing of tumor and non-tumor liver tissue. Hierarchical clustering of ALDH genes was used to identify patient groups and correlations were established with overall survival, recurrence and histological features.
Fifty-two patients were included with 88.5% males, 84.6% with only one HCC and 73.1% with a non-cirrhotic background liver. Median follow-up was 45.7 months. Patients in one cluster defined by its ALDH expression in the tumor tissue showed significantly worse overall survival (log-rank p = 0.015), also when adjusted for age, cirrhosis, microvascular invasion, resection margins and tumor number (hazard ratio 4.2, 95% confidence interval (CI) 1.5-11.9, p = 0.007). When evaluated individually, the isoenzyme ALDH1L1 may be of particular importance. Several clusters in non-tumor tissue were correlated with cirrhosis. Especially one cluster had a high discriminative ability (area under receiver operating characteristic curve of 0.839) and remained significantly associated with cirrhosis when corrected for age, microvascular invasion, resection margins and tumor number (odds ratio 44.2, 95% CI 5.5-352.0, p < 0.001). The combination of ALDH and a previously identified candidate biomarker (expression signature of the transcriptional targets of the peroxisome proliferator-activated receptors (PPARs)) may add additional prognostic value.
The expression of ALDH family members in HCC was correlated with overall survival. Moreover, ALDH expression in non-tumor liver tissue was correlated with cirrhosis. Members of the ALDH family of enzymes may serve as a prognostic biomarker as well as potential targets for systemic treatment.
醛脱氢酶（ALDH）同工酶家族的几个成员已被提议作为肝细胞癌（HCC）患者的预后生物标志物。本研究的目的是通过 RNA 测序和层次聚类评估肿瘤和相邻肝组织中总 ALDH 家族成员的表达，以预测生存并评估其与接受 HCC 肝切除术患者的肝硬化的相关性。
我们纳入了 2014 年 5 月至 2018 年 1 月期间在丹麦哥本哈根大学医院（Rigshospitalet）的三级转诊大学医院接受 HCC 肝切除术的患者。通过对肿瘤和非肿瘤肝组织进行 RNA 测序评估 ALDH 家族成员的表达。使用 ALDH 基因的层次聚类来识别患者组，并建立与总生存率、复发和组织学特征的相关性。
共纳入 52 例患者，其中 88.5%为男性，84.6%仅有一个 HCC，73.1%为非肝硬化背景肝脏。中位随访时间为 45.7 个月。肿瘤组织中 ALDH 表达定义的一个聚类中的患者，其总体生存率显著更差（对数秩检验 p = 0.015），即使在调整年龄、肝硬化、微血管侵犯、切缘和肿瘤数量后也是如此（风险比 4.2，95%置信区间（CI）1.5-11.9，p = 0.007）。当单独评估时，同工酶 ALDH1L1 可能特别重要。非肿瘤组织中的几个聚类与肝硬化相关。特别是一个聚类具有较高的判别能力（接受者操作特征曲线下面积为 0.839），并且在纠正年龄、微血管侵犯、切缘和肿瘤数量后仍然与肝硬化显著相关（比值比 44.2，95%CI 5.5-352.0，p < 0.001）。ALDH 与先前确定的候选生物标志物（过氧化物酶体增殖物激活受体（PPARs）转录靶标的表达特征）的组合可能会增加额外的预后价值。
HCC 中 ALDH 家族成员的表达与总体生存率相关。此外，非肿瘤肝组织中的 ALDH 表达与肝硬化相关。ALDH 家族酶的成员可能既可以作为预后生物标志物，也可以作为系统治疗的潜在靶点。
