In Vivo Staging the Progression of Colitis and Associated Cancer by Concurrent Microimaging of Key Biomarkers

Currently colorectal cancer (CRC) staging (colitis, adenoma,andcarcinoma) mainly relies on ex vivo pathologic analysis requiringan invasive surgical process with limited sample collection and increasedmetastatic risk. Thus, in vivo noninvasive pathological diagnosisis extremely demanded. By verifying the samples of clinical patientsand CRC mouse models, it was found that vascular endothelial growthfactor receptor 2 (VEGFR2) was barely expressed in the colitis stageand only appeared in adenoma and carcinoma stages with obvious elevation,while prostaglandin E receptor 4 (PTGER4) could be observed from colitisto adenoma and carcinoma stages with a gradient increase of expression.VEGFR2 and PTGER4 were further chosen as key biomarkers for molecularpathological diagnosis in vivo and corresponding molecular probeswere constructed. The feasibility of in vivo noninvasive CRC stagingby concurrent microimaging of dual biomarkers using confocal laserendoscopy (CLE) was verified in CRC mouse models and further confirmedby ex vivo pathological analysis. In vivo CLE imaging exhibited thecorrelation of severe colonic crypt structural alteration with a higherbiomarker expression in adenoma and carcinoma stages. This strategyshows promise in benefiting patients undergoing CRC progression within-time, noninvasive, and precise pathological staging, thus providingvaluable guidance for selecting therapeutic strategies.

Automated summary

Currently, the staging of colorectal cancer (CRC) relies on ex vivo pathologic analysis which is invasive and limits sample collection. In this study, key biomarkers VEGFR2 and PTGER4 were selected based on their expression patterns in different stages of CRC. Molecular probes were constructed, and the feasibility of in vivo noninvasive CRC staging using confocal laser endoscopy (CLE) was demonstrated in mouse models. This strategy shows promise in providing precise pathological staging for CRC patients and guiding therapeutic strategies.