Transcription enhanced associate domain factor 1 (TEAD1) predicts liver regeneration outcome of ALPPS-treated patients

IF 2.7 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Hpb Pub Date : 2025-04-01 DOI:10.1016/j.hpb.2024.12.007

Mirco Küchler , Mareike Ehmke , Kai Jaquet , Peter Wohlmuth , Johannes M. Feldhege , Tim Reese , Thilo Hartmann , Richard Drexler , Tessa Huber , Thorsten Burmester , Karl J. Oldhafer

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引用次数: 0

Abstract

Background

The two-stage surgical technique of associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) enables extensive liver resection and promotes future liver remnant regeneration (FLR), in part by inhibiting the Hippo signalling pathway. Its main effector, Yes-associated protein (YAP), has low intrinsic transcriptional activity and requires the transcription enhanced associated domain factor (TEAD) family members as cofactors for target gene transcription. We evaluated the intracellular localization and expression of TEAD1-4, hypothesized to regulate the activity of YAP and, consequently, liver regeneration.

Methods

The intracellular localization of TEAD1-4 was characterized in tumor-free liver (TFL) tissue samples from 44 ALPPS patients obtained during the two stages of ALPPS surgery. Expression levels were correlated with clinical and pathological data as well as liver regeneration metrics.

Results

TEAD family members are simultaneously expressed in individual hepatocytes and show relations with liver regeneration, clinical outcome and outcome parameters when comparing TFL tissue obtained at different stages of ALPPS surgery. Furthermore, differences in TEAD expression and localization within hepatocytes appeared to be independent of global factors.

Conclusion

TEAD1-4 expression correlates with liver regeneration outcomes. Specifically, cytoplasmic and nuclear expression scores of TEAD1 serve as predictive markers for clinical outcomes following ALPPS.

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转录增强相关结构域因子1 （TEAD1）预测alpps治疗患者的肝再生结果。

背景：分阶段肝切除术（ALPPS）的相关肝分区和门静脉结扎两阶段手术技术可以实现广泛的肝切除，并促进未来的肝残体再生（FLR），部分原因是通过抑制Hippo信号通路。其主要效应物Yes-associated protein （YAP）具有较低的内在转录活性，需要转录增强相关结构域因子（TEAD）家族成员作为靶基因转录的辅助因子。我们评估了TEAD1-4的细胞内定位和表达，假设它可以调节YAP的活性，从而调节肝脏再生。方法：对44例ALPPS患者在两期手术中获得的无瘤肝（TFL）组织样本进行TEAD1-4细胞内定位。表达水平与临床和病理数据以及肝脏再生指标相关。结果：在比较ALPPS手术不同阶段获得的TFL组织时，TEAD家族成员在个体肝细胞中同时表达，并与肝再生、临床结局和结局参数相关。此外，肝细胞内TEAD表达和定位的差异似乎与全局因素无关。结论：TEAD1-4的表达与肝再生结果相关。具体而言，TEAD1的细胞质和细胞核表达评分可作为ALPPS临床结果的预测指标。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Hpb GASTROENTEROLOGY & HEPATOLOGY-SURGERY

CiteScore

5.60

自引率

3.40%

发文量

244

审稿时长

57 days

期刊介绍： HPB is an international forum for clinical, scientific and educational communication. Twelve issues a year bring the reader leading articles, expert reviews, original articles, images, editorials, and reader correspondence encompassing all aspects of benign and malignant hepatobiliary disease and its management. HPB features relevant aspects of clinical and translational research and practice. Specific areas of interest include HPB diseases encountered globally by clinical practitioners in this specialist field of gastrointestinal surgery. The journal addresses the challenges faced in the management of cancer involving the liver, biliary system and pancreas. While surgical oncology represents a large part of HPB practice, submission of manuscripts relating to liver and pancreas transplantation, the treatment of benign conditions such as acute and chronic pancreatitis, and those relating to hepatobiliary infection and inflammation are also welcomed. There will be a focus on developing a multidisciplinary approach to diagnosis and treatment with endoscopic and laparoscopic approaches, radiological interventions and surgical techniques being strongly represented. HPB welcomes submission of manuscripts in all these areas and in scientific focused research that has clear clinical relevance to HPB surgical practice. HPB aims to help its readers - surgeons, physicians, radiologists and basic scientists - to develop their knowledge and practice. HPB will be of interest to specialists involved in the management of hepatobiliary and pancreatic disease however will also inform those working in related fields. Abstracted and Indexed in: MEDLINE® EMBASE PubMed Science Citation Index Expanded Academic Search (EBSCO) HPB is owned by the International Hepato-Pancreato-Biliary Association (IHPBA) and is also the official Journal of the American Hepato-Pancreato-Biliary Association (AHPBA), the Asian-Pacific Hepato Pancreatic Biliary Association (A-PHPBA) and the European-African Hepato-Pancreatic Biliary Association (E-AHPBA).