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Proteomic Biomarkers For CNS Lymphoma

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Researchers from the University of California, San Francisco, and biomarker-discovery firm PPD have used a liquid chromatography-mass spectrometry based method to identify a battery of proteins differentially expressed in cerebrospinal fluid, in what they say is the first study in which a proteomic analysis of CSF yielded biomarkers with greater sensitivity than cytology.

The researchers combined high-resolution LC/MS data for profiling differential quantification without isotope labeling with LC/MS/MS for protein identification, and found 76 proteins in CSF associated with central nervous system lymphoma, including a majority that had not been previously identified.

The study, which appears in the Jan. 1 edition of the Journal of Clinical Oncology, demonstrates that "the CSF proteome contains a wealth of potential diagnostic and prognostic information," the authors report.

The researchers say trying to pinpoint the cause of focal brain lesions in patients with unexplained neurological symptoms is a clinical challenge. Diagnostic methods for CNS lymphoma include flow cytometry and, in some cases, measuring beta-human chorionic gonadotropin or alpha-fetoprotein levels.

James Rubenstein, senior author of the study and an assistant professor of hematology and oncology at UCSF, says that among approaches using CSF, cytology is the "gold standard" in diagnosing brain cancer. However, the sensitivity of the method to diagnose lymphoma and other cancers is less than 50 percent.

The diagnostic method of last resort is brain biopsy, but in addition to a risk for brain hemorrhaging, the method carriers a failure rate as high as 35 percent.

Earlier research suggests that the elevation of total CSF proteins may be associated with adverse prognosis in CNS lymphoma, although the identity of specific proteins and peptides had not been known. In addition, mass spectrometry has been shown to be able to detect such proteins to help diagnose certain cancers early in their development.

Tony Fong

Proteomics Notes

Plexera has exclusive access to Auguron Biosciences' Nucleic Acid Programmable Protein Array technology for one year, with an option for a one-year extension. Plexera will be testing and developing NAPPA as a content source for its own label-free Kx Array platform.

Fluorotechnics, an Australian biotech firm, announced a partnership with Japan's Wako Pure Chemical Industries. Under their agreement, Wako will sell Fluorotechnics' fluorescence-based kits as well as its protease monitoring and live-cell intracellular imaging technologies.

Nacalai Tesque and Nacalai USA will distribute Olink Bioscience's Duolink products in Japan. Duolink uses Olink's in situ Proximity Ligation Assay technology.

Datapoint

$6.25 million
CS-Keys, a proteomics firm that is developing technology for cancer biomarker detection, raised $6.25 million in Series A financing.

Funded grants

$58,886/FY2007
A proteomics approach to study the mechanisms of Fas-induced lung fibrosis
Grantee: Dong Chang, University of Washington
Began: Aug. 3, 2007; Ends: Aug. 8, 2008
To study acute respiratory distress syndrome and the Fas pathway involved in lung injury, the researchers will use mice with Fas on their myeloid or non-myeloid cells to study how alveolar epithelium and alveolar macrophages contribute to lung fibrosis. Through proteomic analysis, they will look at mouse bronchoalveolar lavage fluid and determine how MMP-12 modifies profibrotic proteins.

$229,500/FY2007
Plasma Proteome Profiling of Insulin Resistance
Grantee: Nana Gletsu, Emory University
Began: Apr. 1, 2007; Ends: Mar. 31, 2009
Under this grant, researchers will perform a proteomic analysis of insulin resistance to find biomarkers. They will study intravenous glucose tolerance tests and oxidative stress and inflammation of patients as they undergo a gastric bypass or are on a low-calorie, liquid formula diet. Also, using LC/MS/MS, they will identify proteins associated with differences in insulin resistance in obese patients who lose weight.

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