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

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.