Bioinformatics Seminar
Time: 11AM
Venue: Davis Auditorium and Online
8 October 2024
NACharacterisation of the head and neck tumour microenvironment using high plex spatial technologies and analysis
Chin Wee TanWEHI Bioinformatics
Head and neck squamous cell carcinoma (HNSCC) is a debilitating disease that accounts for an estimated 890,000 new cases per year, making it the seventh most common cancer globally. Despite advancements in chemotherapy, radiotherapy, surgery and immunotherapy, the prognosis of HNSCC has remained relatively unchanged for more than a decade. There is a need to better understand of the tumour microenvironment (TME) using spatially resolved approaches, to gain insights into the TME associated with clinical endpoints such as Disease-Free Survival (DFS) and Overall Survival (OS). Here we utilised state of the art high plex spatial profiling technologies to interrogate 84 HNSCC tissue samples using either the NanoString’s GeoMX DSP IPA (580-proteins) or DSP Whole Transcriptome Atlas (18,000 mRNA, WTA) assay. We used our R package standR and an ensemble of survival analysis approaches to analyse and compare across the two assays. Till this end, we found that patient survival outcomes (both DFS and OS) were associated with anatomical locations and tumour stage. Notably, there were specific proteomic and transcriptomic features in both the tumour and stromal regions that associated with DFS and OS. These key proteomic findings (including CD34 and CD44) were independent validated using single-cell protein profiling (PhenoCycler-Fusion, Akoya Biosciences). Finally, cell type deconvolution based on transcriptomic signatures revealed cell types associated with patient survival. Taken together, this study provides a systematic workflow for discovery and validation of high-plex protein and transcriptomic profiling in HNSCC.