Colorectal cancer is a predominant malignancy with a
second mortality
worldwide. Despite its prevalence, therapeutic options remain constrained
and surgical operation is still the most useful therapy. In this regard,
a comprehensive spatially resolved quantitative proteome atlas was
constructed to explore the functional proteomic landscape of colorectal
cancer. This strategy integrates histopathological analysis, laser
capture microdissection, and proteomics. Spatial proteome profiling
of 200 tissue section samples facilitated by the fully integrated
sample preparation technology SISPROT enabled the identification of
more than 4000 proteins on the Orbitrap Exploris 240 from 2 mm2 × 10 μm tissue sections. Compared with normal
adjacent tissues, we identified a spectrum of cancer-associated proteins
and dysregulated pathways across various regions of colorectal cancer
including ascending colon, transverse colon, descending colon, sigmoid
colon, and rectum. Additionally, we conducted proteomic analysis on
tumoral epithelial cells and paracancerous epithelium from early to
advanced stages in hallmark rectum cancer and sigmoid colon cancer.
Bioinformatics analysis revealed functional proteins and cell-type
signatures associated with different regions of colorectal tumors,
suggesting potential clinical implications. Overall, this study provides
a comprehensive spatially resolved functional proteome landscape of
colorectal cancer, serving as a valuable resource for exploring potential
biomarkers and therapeutic targets.