Models that combine transcriptomic with spatial protein information exceed the predictive value for either single modality

Abstract

Immunotherapy has reshaped the field of cancer therapeutics but the population that benefits are small in many tumor types, warranting a companion diagnostic test. While immunohistochemistry (IHC) for programmed death-ligand 1 (PD-L1) or mismatch repair (MMR) and polymerase chain reaction (PCR) for microsatellite instability (MSI) are the only approved companion diagnostics others are under consideration. An optimal companion diagnostic test might combine the spatial information of IHC with the quantitative information from RNA expression profiling. Here, we show proof of concept for combination of spatially resolved protein information acquired by the NanoString GeoMx® Digital Spatial Profiler (DSP) with transcriptomic information from bulk mRNA gene expression acquired using NanoString nCounter® PanCancer IO 360™ panel on the same cohort of immunotherapy treated melanoma patients to create predictive models associated with clinical outcomes. We show that the combination of mRNA and spatially defined protein information can predict clinical outcomes more accurately (AUC 0.97) than either of these factors alone.