Spatiotemporal Proteomics: Unveiling Evolving Molecular Landscapes in Inflammatory Bowel Disease and Associated Colorectal Cancer.

Spatiotemporal proteomics, as a vital component of spatiotemporal omics, possesses the capability to conduct large-scale screening and analysis of protein molecules across different spatial and temporal dimensions under various physiological or pathological conditions. This enables a precise and visualizable landscape of molecular distribution and expression changes. This technology is progressively becoming the most cutting-edge and effective tool in research on various diseases, including inflammatory bowel disease (IBD) and its associated colorectal cancer (CRC). Digital spatial profilers, imaging mass spectrometry, and imaging mass cytology have become widely adopted spatiotemporal proteomics technologies in IBD and CRC research due to their advantages of high-throughput, high-specificity, and single-cell resolution. In IBD research, these techniques not only help analyze the changes in protein distribution within intrinsic muscle layer cells, intestinal epithelial cells, and immune cells but also help examine the distribution and expression differences within the gut microbiota. In CRC research, spatiotemporal proteomics primarily focuses on molecular dynamic changes occurring across different stages of CRC (initiation, progression, and metastasis), including cellular distribution and differential expression of relevant molecules within the peritumoral region and alterations in the distribution of protein molecules across cellular compartments. Moreover, the translational applications of spatiotemporal proteomics warrant equal attention. These extend beyond screening traditional molecular therapeutic targets to encompass the development of precision therapies and adjunctive treatments (hyperbaric oxygen therapy, kinesitherapy, and controlled location and timing of medication). This review summarized the strengths and limitations of spatiotemporal proteomics technologies widely applied in IBD and CRC; described the spatial and temporal landscapes revealed by these techniques, elucidating their applications in diagnosis, treatment, and prognosis; and finally outlined the feasible directions for future optimization and advancement of spatiotemporal proteomics.