CC BY-NC-ND 4.0 · Laryngorhinootologie 2019; 98(S 02): S87
DOI: 10.1055/s-0039-1686100
Abstracts
Oncology

KLK6-dependent gene expression signature as a prognostic marker in head and neck carcinomas

K Zaoui
1   HNO-Universitätsklinik Heidelberg, Heidelberg
,
T Pompecki
1   HNO-Universitätsklinik Heidelberg, Heidelberg
,
A Jou
1   HNO-Universitätsklinik Heidelberg, Heidelberg
,
A Nollert
1   HNO-Universitätsklinik Heidelberg, Heidelberg
,
C Shao
2   Division of Molecular Neurogenetics, German Cancer Research Center, Heidelberg
,
X Pastor Hostench
3   Division of Theoretical Bioinformatics, German Cancer Research Center, Heidelberg
,
A Hiou Feige
4   Head and Neck Tumor Laboratory, Department of Otolaryngology-Head and Neck Surgery, CHUV and University of Lausanne, Lausanne, Schweiz
,
G Tolstonog
4   Head and Neck Tumor Laboratory, Department of Otolaryngology-Head and Neck Surgery, CHUV and University of Lausanne, Lausanne, Schweiz
,
L Schroeder
5   Division of Molecular Diagnostics of Oncogenic Infections, Infection, Inflammation and Cancer Program, German Cancer Research Center, Heidelberg
,
J Hess
1   HNO-Universitätsklinik Heidelberg, Heidelberg
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    Epithelial-to-mesenchymal transition (EMT) is a dynamic process and critically contributes to treatment resistance, cancer cell dissemination and metastasis. Main objective of this study was to investigate the functional interaction between Kallikrein-related peptidase 6 (KLK6) and aldehyde dehydrogenase 1A (ALDH1A)-related retinoic acid (RA) signaling as recent studies reported their impact on molecular features resembling EMT in several malignancies, including head and neck squamous cell carcinoma (HNSCC). In HNSCC cell lines, we demonstrate that KLK6 is not only a downstream target of ALDH1A-related RA signaling, but also acts as an upstream regulator of ALDH1A3 expression. KLK6 and ALDH1A3 co-expression was confirmed in a mouse xenograft model and two independent HNSCC cohorts (HIPO-HNC and TCGA-HNC). KLK6 and ALDH1A3 co-expressed genes in HNSCC, which are also differentially expression in HNSCC cells with silenced KLK6 expression unraveled several subgroups of HNSCC patients with distinct histopathological and clinical features. In summary, our study highlights a new functional circuit with KLK6 and ALDH1A3 as key nodes and unraveled a gene expression signature, which predicts unfavorable prognosis in human papilloma virus (HPV)-negative HNSCC.


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    Dr. Karim Zaoui
    HNO-Universitätsklinik Heidelberg,
    Im Neuenheimer Feld 400, 69120
    Heidelberg

    Publication History

    Publication Date:
    23 April 2019 (online)

    © 2019. 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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