Spatial proteogenomics in oncology: linking molecular positivity to tissue context

Tumor biomarker assessment has traditionally focused on two simple questions: whether a marker is expressed and how strongly it is expressed. This method can still be useful but it is no longer sufficient. The meaning of a marker may vary according to its tissue location, neighboring cell types, and association with a treatment-related microenvironment. As spatial omics technologies progress, cancer research is moving beyond a simple positive-or-negative interpretation of molecular markers. It is therefore important to ask where a marker is positive, which cells are nearby, and whether it is part of an active tissue structure. Spatial proteogenomics brings together protein measurements, transcriptomics, spatial tissue imaging and bioinformatics. This allows for the integration of molecular state, cell state and spatial information. This mini review discusses what this change means for oncology. It focuses on the spatial chain of evidence, the tumor microenvironment, spatial functional units, and the challenge of turning spatial maps into measurements that can be used in the clinic.