New Tumor-Budding Signature Identified: 28-Gene Tumor-Budding Sequence predicts HNSCC Risk and potential MEK-Inhibitor Therapies

The research group, led by Melanie Boxberg and Fabian Stögbauer, in collaboration with colleagues from the University Hospital Heidelberg, conducted a study on tumour budding in HPV-negative head and neck squamous cell carcinoma (HNSCC). Utilising spatial transcriptomic analyses, they revealed that tumour buds exhibit a distinct molecular programme. The aetiology of this condition is multifactorial, involving a combination of genetic factors, partial epithelial-mesenchymal transition, hypoxemia, and matrix remodelling. The analysis yielded a 28-gene tumour-budding signature (TBS), which is capable of identifying tumour buds with a high degree of precision and reliably distinguishing HNSCC cases with tumour budding from those without, as evidenced by independent bulk RNA-seq data sets. A high TBS has been shown to be associated with a reduced overall survival time, thus constituting an independent prognostic factor. Single-cell analyses reveal that the TBS is predominantly expressed in malignant tumour cells at the invasive margin and is associated with elevated levels of EGFR and MAPK pathway activity. Functional experiments in the study further suggest that TBS-high tumors are particularly sensitive to MEK inhibitors. These analyses could therefore help to improve the treatment of patients with HNSCC.

Ourailidis I, Ball M, Vogel V, He M, Wang H, Kim SB, Böning S, Wollenberg B, Wolff KD, Steiger K, Mogler C, Duensing A, Duensing S, Schirmacher P, Stenzinger A, Gires O, Kazdal D, Kirchner M*, Stögbauer F*, Boxberg M* & Budczies J*. Spatial transcriptomics reveals a molecular tumor budding signature in head and neck cancer. Genome Med (2026); 18: 10.1186/s13073-026-01612-2. PMID: 41987303