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Spatial Transcriptomic Analysis of Surgical Resection Specimens of Primary Head and Neck Squamous Cell Carcinoma
Simon Beyaert1,2, Axelle Loriot3, Jean-Pascal Machiels1,4
1Institut de Recherche Expérimentale et Clinique (IREC), Pôle MIRO, Université Catholique de Louvain (UCLouvain), 1200 Brussels, Belgium.
Abstract:
Afatinib-induced tumor and microenvironment modifications in head and neck squamous cell carcinoma were evaluated by spatial transcriptomics in surgical specimens and RNA-sequencing in tumor biopsies of patients included in the EORTC-90111-24111 window-of-opportunity study. The aim was to explore tumor evolution and composition under anti-HER therapy. Based on our previous investigations by RNA-seq on tumor biopsies, surgical slides of ID08 and ID15 from the epithelial-to-mesenchymal (EMT) cluster and ID30 from the non-EMT cluster were investigated with spatial transcriptomics. Dimension reduction in ID30 revealed 14 clusters, with clusters overlapping three tumor nodules and the stroma. Differential expression analysis between tumor nodules showed enrichment of the hallmark EMT genelist, with 123 genes in common between the analyses. These genes were involved in PDGF and MET signaling pathways. By comparing gene expression in paired tumor biopsies and the 123 genes from differential analyses obtained in ID30, a list of 13 genes involved in cancer pathways and EMT emerged, which were also highly expressed in ID08 and ID15. These results show a progressive apparition of genes implicated in EMT, MET, and PDGF pathways in tumors after afatinib. Notably, a list of 13 genes emerged which may contain targets to prevent tumor evolution after anti-HER therapy.
Insights
Afatinib treatment alters head and neck cancer by promoting epithelial-to-mesenchymal transition (EMT) and activating PDGF and MET pathways. A 13-gene signature may offer targets to prevent tumor evolution under anti-HER therapy.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Head and neck squamous cell carcinoma (HNSCC) is a complex disease.
- Anti-HER therapies, like afatinib, are used to treat HNSCC.
- Understanding tumor evolution under therapy is crucial for treatment optimization.
Purpose of the Study:
- To investigate afatinib-induced modifications in HNSCC tumors and their microenvironment.
- To explore tumor evolution and composition during anti-HER therapy.
- To identify potential therapeutic targets for preventing tumor progression.
Main Methods:
- Spatial transcriptomics on surgical specimens and RNA-sequencing on tumor biopsies.
- Analysis of patients from the EORTC-90111-24111 window-of-opportunity study.
- Differential gene expression analysis and pathway enrichment.
Main Results:
- Afatinib treatment induced progressive changes related to epithelial-to-mesenchymal transition (EMT), MET, and PDGF signaling pathways.
- Spatial transcriptomics identified 14 distinct clusters in tumor samples, including tumor nodules and stroma.
- A core list of 13 genes involved in cancer pathways and EMT was identified, showing high expression in treated tumors.
Conclusions:
- Afatinib therapy drives significant molecular alterations in HNSCC, including EMT and specific signaling pathways.
- The identified 13-gene signature represents potential targets to counteract tumor evolution post-anti-HER therapy.
- Further research into these genes could lead to novel therapeutic strategies for HNSCC.
