Target Discovery and Validation Reviews and Protocols

332 Le Naour
heterogeneity of HCC, which is a multistage process with the involvement of a
multifactorial etiology and many gene–environment interactions.
Finally, the proteomic-based approach, also called serological proteome analysis
(SERPA) (18) or proteome-based target evaluation combined with immunoreactive
target structure identification explored by sera (Proteomex) (19) has been
applied to different types of cancer, such as renal cellular carcinoma; neuroblastoma,
lung, pancreatic, and breast cancers; and HCC (15–25). Several autoantigens
have been identified that may have clinical applications in diagnosis as well as in
determining prognosis.
3.4. Alternative Proteomic-Based Approaches and Future Directions
The screening and identification of proteins that elicit humoral response
in cancer have been performed recently by alternative methods (see Chapters 14
and 15, Volume 1). Indeed, a proteomic-based methodology called antibodymediated
identification of antigens (AMIDA) has been set up (26). The approach
is based on immunoprecipitation experiments using antibodies from serum of
healthy individuals or patients with cancer. The method has been applied for
TAA identification in head and neck cancer, and 12 proteins were identified (27).
Three of the proteins exhibited overexpression in carcinomas by using immunochemistry
experiments. In addition, elevated circulating antibodies were
observed in serum from patients with cancer (27). Proteomics is now moving on
the analysis of whole proteins in complex mixtures by using gel-free separation
techniques. For example, protein biochips (or microarrays) are emerging in different
formats as an alternative to 2DE for differential expression analysis at the protein
level (28). Microarrays of tumor cell-derived proteins have uncovered
immunogenic proteins and autoantibodies in serum from patients with prostate,
colon, and lung cancer (see also Chapter 17, Volume 1) (28–30).
3.5. Conclusions
Proteomics has emerged recently and is making great progress very rapidly.
Proteomic-based approaches have already permitted screening and identification
of TAAs that were not obtained using classical approaches. These proteins
have a potential clinical utility and may serve as novel cancer markers in
screening, diagnosis, or prognosis. It is likely that proteomics will play an
important role in the discovery of new TAAs and perhaps in the development of
personalized medicines.
4. Notes
1. 2D-PAGE is a very high-resolution separation technique.
2. 2D-PAGE is not adapted for proteins having extreme molecular weight or for proteins
that are highly hydrophobic (e.g., membrane proteins).