Challenges for biomarker discovery in body fluids using SELDI-TOF-MS

Abstract

Protein profiling using SELDI-TOF-MS has gained over the past few years an increasing interest in the field of biomarker discovery. The technology presents great potential if some parameters, such as sample handling, SELDI settings, and data analysis, are strictly controlled. Practical considerations to set up a robust and sensitive strategy for biomarker discovery are presented. This paper also reviews biological fluids generally available including a description of their peculiar properties and the preanalytical challenges inherent to sample collection and storage. Finally, some new insights for biomarker identification and validation challenges are provided.

Figure 1

Effects of different ProteinChip array surfaces and wash conditions. The combination of ProteinChip array surface types and wash conditions maximize the potential for protein biomarker discovery.

Figure 2

Experimental variables that can affect proteomics data. Most of the steps shown are involved in all proteomics workflows, but SELDI technology performs many of them on a single platform.

Figure 3

Protein mass spectra collected on CM10 and IMAC-Cu²⁺ ProteinChip arrays with serum samples provided by five patients with arthritidies (including rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis) and five noninflammatory controls (NIC) (including osteoarthritis). (a) The inflammatory-related proteins S100A8, S100A12, S100A9, and one of its variant S100A9* are arthritis biomarkers detected on CM10 arrays. (b) On IMAC-Cu²⁺ ProteinChip arrays, SAA and its 2 variants (SAA-R and SAA-RS) are illustrated, reproduced from [19].

Figure 4

Modified transthyretin forms observed in ovarian cancer sample, adapted from [123].