Moving forward in colorectal cancer research, what proteomics has to tell

Abstract

Colorectal cancer is the third most common cancer and is highly fatal. During the last several years, research has been primarily based on the study of expression profiles using microarray technology. But now, investigators are putting into practice proteomic analyses of cancer tissues and cells to identify new diagnostic or therapeutic biomarkers for this cancer. Because the proteome reflects the state of a cell, tissue or organism more accurately, much is expected from proteomics to yield better tumor markers for disease diagnosis and therapy monitoring. This review summarizes the most relevant applications of proteomics the biomarker discovery for colorectal cancer.

Figure 1

Proteomic differential display methods.

Figure 2

2D-DIGE techniques. Cy2, Cy3 and Cy5 are different fluorescent dyes.

Figure 3

Representation of the two antibody microarray experimental formats. Direct labelling: single-capture antibody experiments; all proteins in a sample are labelled (black circles) thereby providing a means for detecting bound proteins following incubation on an antibody microarray. Dual-antibody (capture and read-out antibody) sandwich immunoassays: proteins captured on an antibody microarray are detected by a cocktail of tagged detection antibodies, which are matched to the spotted antibodies. The detector antibody tag is then measured by binding of a labelled (empty circles) read-out antibody.

Figure 4

Principles of SELDI-TOF MS. The application of sample from to an eight-spot array with hydrophilic, hydrophobic, cationic, anionic or immobilized-metal affinity capture chromatography surface (black colour). The addition of an appropriate binding buffer (purple colour). On-chip sample purification using one or more wash buffers (grey colour). The application of energy-absorbing matrix for the absorption of laser energy (empty colour). Laser irradiation desorbs bound proteins and positively ionizes them. Owing to the electric field, they migrate in the mass analyser: (small diamond) and multiply charged proteins (oval) faster than large and single-charged ones (triangle). Thus, the proteins are separated. Time of flight (t) is proportional to protein mass per charge.

Figure 5

Different strategies for proteomic studies.