Protein biomarkers for early detection of diseases: The decisive contribution of combinatorial peptide ligand libraries.

The present review deals with biomarker discovery, especially in regard to sample treatment via combinatorial peptide ligand libraries, perhaps the only technique at present allowing deep exploration of biological fluids and tissue extracts in search for low- to very-low-abundance proteins, which could possibly mark the onset of most pathologies. Early-stage biomarkers, in fact, might be the only way to detect the beginning of most diseases thus permitting proper intervention and care. The following cancers are reviewed, with lists of potential biomarkers suggested in various reports: hepatocellular carcinoma, ovarian cancer, breast cancer and pancreatic cancer, together with some other interesting applications. Although panels of proteins have been presented, with robust evidence, as potential early-stage biomarkers in these different pathologies, their approval by FDA as novel biomarkers in routine clinical chemistry settings would require plenty of additional work and efforts from the pharma industry. The science environment in universities could simply not afford such heavy monetary investments.

SIGNIFICANCE: After more than 16years of search for novel biomarkers, to be used in a clinical chemistry set-up, via proteomic analysis (mostly in biological fluids) it was felt a critical review was due. In the present report, though, only papers reporting biomarker discovery via combinatorial peptide ligand libraries are listed and assessed, since this methodology seems to be the most advanced one for digging in depth into low-to very-low-abundance proteins, which might represent important biomarkers for the onset of pathologies. In particular, a large survey has been made for the following diseases, since they appear to have a large incidence on human population and/or represent fatal diseases: ovarian cancer, breast cancer, pancreatic cancer and hepatocellular carcinoma.