Regulation and function of UCHL1 in the pathogenesis and therapy of Head and Neck Cancer

 

Emerging in different subsites Head and Neck Squamous Cell Carcinoma (HNSCC) are very heterogenous tumors, thus for treatment optimization a stratification based on molecular features is urgently needed.

In previous studies we noticed UCHL1 positivity in a substantial amount of HNSCC. UCHL1 (ubiquitin C-terminal hydrolase L1) is an established neuronal marker and one of the most abundant proteins in the CNS. The aim of this study is to characterize the molecular features of this UCHL1-positive tumors as a potential novel subgroup of HNSCC.

We used multi-omics data from TCGA-HNSC as a training cohort to perform an integrative analysis and validated our results in independent HNSCC cohorts.

We designed an UCHL1-associated gene signature and identified subgroups with high or low UCHL1 expression. We revealed two UCHL1-high subgroups, both showing high genomic instability and an increased tumor mutational burden (TMB). Both show hypomethylation of UCHL1 and one subgroup is enriched for NSD1 mutations. There were significant differences in the clinical outcome, whereas prominent sonic hedgehog signaling and an immune cold phenotype was associated with bad prognosis.

In conclusion our data highlight the epigenetic, genetic and clinical features of a new UCHL1 associated subgroup, allowing the development of novel therapy concepts targeting these molecular characteristics.

Poster-PDF A-1548.pdf

Publication History

Article published online:
13 May 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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