TY  - JOUR
AU  - Ourailidis, Iordanis
AU  - Stögbauer, Fabian
AU  - Zhou, Yuxiang
AU  - Beck, Susanne
AU  - Romanovsky, Eva
AU  - Eckert, Stephan
AU  - Wollenberg, Barbara
AU  - Wirth, Markus
AU  - Steiger, Katja
AU  - Kuster, Bernhard
AU  - Gires, Olivier
AU  - Stenzinger, Albrecht
AU  - Schirmacher, Peter
AU  - Weichert, Wilko
AU  - Kuhn, Peer-Hendrik
AU  - Boxberg, Melanie
AU  - Budczies, Jan
TI  - Multi-omics analysis to uncover the molecular basis of tumor budding in head and neck squamous cell carcinoma.
JO  - npj precision oncology
VL  - 9
IS  - 1
SN  - 2397-768X
CY  - [London]
PB  - Springer Nature
M1  - DKFZ-2025-00564
SP  - 73
PY  - 2025
AB  - Tumor budding (TB) is a prognostic biomarker in HPV-negative and HPV-positive head and neck squamous cell carcinoma (HNSCC). Analyzing TCGA and CPTAC mutation, RNA, and RPPA data and performing proteomics and IHC in two independent in-house cohorts, we uncovered molecular correlates of TB in an unprecedentedly comprehensive manner. NSD1 mutations were associated with lower TB in HPV-negative HNSCC. Comparing budding and nonbudding tumors, 66 miRNAs, including the miRNA-200 family, were differentially expressed in HPV-negative HNSCC. 3,052 (HPV-negative HNSCC) and 360 (HPV-positive HNSCC) RNAs were differentially expressed. EMT, myogenesis, and other cancer hallmarks were enriched in the overexpressed RNAs. In HPV-negative HNSCC, 88 proteins were differentially expressed, significantly overlapping with the differentially expressed RNAs. CAV1 and MMP14 protein expression investigated by IHC increased gradually from nonbudding tumors to the bulk of budding tumors and tumor buds. The molecular insights gained support new approaches to therapy development and guidance for HNSCC.
LB  - PUB:(DE-HGF)16
C6  - pmid:40082664
C2  - pmc:PMC11906922
DO  - DOI:10.1038/s41698-025-00856-2
UR  - https://inrepo02.dkfz.de/record/299827
ER  -