Researchers at the Memorial Sloan-Kettering Cancer Center have found that the degradation products of relatively high-abundance blood proteins, which had previously been dismissed by some as waste products that serve no diagnostic purpose, may actually serve as good biomarkers for disease.
While the disease-specific proteases themselves are not abundant enough in blood to be seen by regular proteomics experiments, the serum peptidome, which contains disease-specific cleavage fragments of known proteins and peptides, could serve as a new type of biomarker, Tempst says.
“Basically, we were lucky to pick up this activity,” Tempst says. “There are a lot of low-concentration enzymes you can’t see, but if you give them enough time and enough substrate, you can get a catalytic product that’s measurable with MALDI-TOF.”
Lance Liotta and Emanuel Petricoin wrote in a commentary that accompanied the paper that while some researchers have dismissed the serum peptidome as “biological trash,” Tempst’s work shows that the peptidome may, in fact, contain “diagnostic gold.”
“The implications for the diagnostics arena are enormous,” wrote Liotta and Petricoin, both researchers at George Mason University. “Fingerprints of MS ions can be replaced with panels of named protein biomarkers.”
Benjamin Cravatt, a proponent of “activity-based proteomics” at the Scripps Research Institute, concurs. “This work is highly significant because it provides evidence that different tumor types secrete and/or shed distinct sets of proteases that, through their catalytic activity, generate unique serum peptide profiles,” according to Cravatt. “These peptide profiles can in turn be used as patterns to accurately predict the presence of a particular tumor type in patients.”
This patent protects an invention relating to “an LC/MS interface provided with structure that the end of a spray capillary is rarely damaged and the object is to provide the LC/MS interface which a general user can easily operate, which inhibits the extension of a separation band and the deterioration of detection sensitivity, and which enables high separation and sensitive analysis,” according to the abstract.
This patent deals with “a mass spectrometer having a matrix-assisted laser desorption ionization (MALDI) source which operates at ambient pressure” as well as with methods to operate the instrument, according to the abstract.