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

K Zaoui; T Pompecki; A Jou; A Nollert; C Shao; X Pastor Hostench; A Hiou Feige; G Tolstonog; L Schroeder; J Hess

doi:10.1055/s-0039-1686100

Laryngo-Rhino-Otologie, Table of Contents

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

Authors

K Zaoui

¹HNO-Universitätsklinik Heidelberg, Heidelberg
T Pompecki

¹HNO-Universitätsklinik Heidelberg, Heidelberg
A Jou

¹HNO-Universitätsklinik Heidelberg, Heidelberg
A Nollert

¹HNO-Universitätsklinik Heidelberg, Heidelberg
C Shao

²Division of Molecular Neurogenetics, German Cancer Research Center, Heidelberg
X Pastor Hostench

³Division of Theoretical Bioinformatics, German Cancer Research Center, Heidelberg
A Hiou Feige

⁴Head and Neck Tumor Laboratory, Department of Otolaryngology-Head and Neck Surgery, CHUV and University of Lausanne, Lausanne, Schweiz
G Tolstonog

⁴Head and Neck Tumor Laboratory, Department of Otolaryngology-Head and Neck Surgery, CHUV and University of Lausanne, Lausanne, Schweiz
L Schroeder

⁵Division of Molecular Diagnostics of Oncogenic Infections, Infection, Inflammation and Cancer Program, German Cancer Research Center, Heidelberg
J Hess

¹HNO-Universitätsklinik Heidelberg, Heidelberg

Abstract

Full Text

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.