Table V

Some open questions related to diagnostic SELDI-TOF technologya

1.Identity and serum concentration of discriminating molecules not known. Mass spectrometry is a largely qualitative technique. Relationship between peak height and molecule abundance is not linear and could be very complex.
2.Discriminating peaks identified by different investigators for the same disease are different.
3.Data not easily reproducible between laboratories, making validation difficult.
4.Optimal sample preparation for the same disease differs between investigators. Sample handling and preparation may be a critical issue.
5.Validated serum cancer markers (e.g. PSA, CA125, etc.) that could serve as positive controls are not identified by this technology.
6.Nonspecific absorbtion matrices favor extraction of high-abundance proteins/peptides at the expense of low-abundance proteins/peptides. Unknown recovery of “informative” molecules versus “uninformative” molecules. Analytical sensitivity of mass spectrometry in the context of these experiments is not known.
7.Technique likely measures peptides or other molecules present in high abundance in serum (e.g. mg/liter to g/liter range). Such molecules are unlikely to originate from cancer tissue. More likely, they represent cancer epiphenomena.
8.No known relationship between discriminatory molecules and cancer biology.
  • a This table is reproduced from Ref. 46 with permission from the copyright owners.