Absolute Proteome Analysis of Colorectal Mucosa, Adenoma, and Cancer Reveals Drastic Changes in Fatty Acid Metabolism and Plasma Membrane Transporters

Colorectal cancer is a leading cause
of cancer-related death. It
develops from normal enterocytes, through a benign adenoma stage,
into the cancer and finally into the metastatic form. We previously
compared the proteomes of normal colorectal enterocytes, cancer and
nodal metastasis to a depth of 8100 proteins and found extensive quantitative
remodeling between normal and cancer tissues but not cancer and metastasis
(Wiśniewski et al. PMID 22968445). Here we utilize advances
in the proteomic workflow to perform an in depth analysis of the normal
tissue (N), the adenoma (A), and the cancer (C). Absolute proteomics
of 10 000 proteins per patient from microdissected formalin-fixed
and paraffin-embedded clinical material established a quantitative
protein repository of the disease. Between N and A, 23% of all proteins
changed significantly, 17.8% from A to C and 21.6% from N to C. Together
with principal component analysis of the patient groups, this suggests
that N, A, and C are equidistant but not on one developmental line.
Our proteomics approach allowed us to assess changes in varied cell
size, the composition of different subcellular components, and alterations
in basic biological processes including the energy metabolism, plasma
membrane transport, DNA replication, and transcription. This revealed
several-fold higher concentrations of enzymes in fatty acid metabolism
in C compared with N, and unexpectedly, the same held true of plasma
membrane transporters.