Spatial transcriptomics reveals distinct and conserved tumor core and edge architectures that predict survival and targeted therapy response

Abstract We performed the first integrative single-cell and spatial transcriptomic analysis on HPV-negative oral squamous cell carcinoma (OSCC) to comprehensively characterize tumor core (TC) and leading edge (LE) transcriptional architectures. We show that the TC and LE are characterized by unique transcriptional profiles, cellular compositions, and ligand-receptor interactions. We demonstrate that LE regions are conserved across multiple cancers while TC states are tissue specific, highlighting the existence of common mechanisms underlying tumor progression and invasion. Additionally, we found that a LE gene signature is associated with worse clinical outcomes while a TC gene signature is associated with improved prognosis across multiple cancer types. Finally, using an in silico modeling approach, we describe spatially-regulated patterns of cell development in OSCC that are predictably associated with drug response. Our work provides pan-cancer insights into TC and LE biology and an explorable atlas (http://www.pboselab.ca/spatial_OSCC/) that can be foundational for developing novel targeted therapies.