Monday, September 1, 2008

JBNI Lung Cancer Early Detection and Biomarker Identification Technology

Background: Symptoms of lung cancer (LC) often do not appear until the disease is advanced; only 15% of LC cases are discovered while the tumor is in the early stages of development. Carcinogen exposure, asthma and smoking have been identified as risk factors for the development of LC. Early detection of LC will likely have a major impact on the natural history of the disease and facilitate curative treatment. The objective of the study was to apply mass spectrometric (MS) methods to identify a panel of biomarkers for early detection of LC.

Methods: Normal serum controls (NO; n = 30) from healthy volunteers and lung cancer patients (LC; n = 30) were acquired from a commercial vendor. Baseline pre-treatment) serum specimens from individuals with asthma (AST; n = 28) and lung cancer risk (LCR; n = 73) were available from clinical trials of two novel agents that are being developed by JBNI Inc. Serum proteins were analyzed using liquid chromatography electrospray ionization mass spectrometry (LC-ESIMS MS) to identify biomarkers that are expressed in a significantly different manner in individuals with LC, LCR, or AST in comparison with NO subjects. Specimens were digested with trypsin and analyzed by LC-ESIMS. Data were analyzed using Mascot search software.

Results: We have identified a number of heretofore unrecognized differentially expressed proteins in LC, LCR and AST samples relative to NO samples. The identified proteins include putative expressed proteins identified in prior genetic sequencing efforts, several patented proteins having functions that have not been described in the literature, a protein involved in intracytoplasmic protein membrane anchorage, a proteasome component, cellular immune response, as well as several MHC associated proteins.

Conclusions: Our results support an extended MS analysis of serum biomarker profiles as a supplementary tool in the identification of target molecules and systems for the subsequent application of quantitative validation techniques for the identification and molecular characterization of the condition and development of novel agents for prevention, early detection and treatment of LC.