Colorectal cancer is one of the most common cancers in hnmans. Studying proteotranscriptomics data conld be essential to discovering signature pathways in colorectal cancer progression. Herein, we conducted a proteotranscriptomics analysis to identify pathway differences of cancer progression at the transcript and protein levels, each of which was represented by an independent colorectal cancer study containing tumor and adjacent normal samples. As a result, additional information on pathways at the protein level showed signature pathways associated with colorectal cancer progression which might not have been revealed at the transcript level. Information on the focal adhesion pathway related to actin cytoskeletal regulation and cancer pathways was preserved only at the protein level. Meanwhile, an oxidative phosphorylation pathway, that was highly correlated with the neurodegenerative Alzheimer, Huntington, and Parkinson diseases, was preserved at both the transcript and protein levels. This pilot study also suggests that both focal adhesion and oxidative phosphorylation could be potential colorectal cancer therapeutic targets.