The themes of discovery and validation resonated throughout the conference. Dr. Schiess presented a two-stage strategy for discovery and initial validation of serum biomarkers corresponding to specific cancer-causing mutations that involved the use of mass spec assisted discovery, verification, and validation of disease biomarkers. “I take a systems approach and study the mechanisms of the disease by using a mouse model to study tumors with silent progression,” he said. “I used prostate cancer as a model, but I believe applications can be made to other cancers as well.”
Dr. Schiess integrated his study of mouse genetics with proteomics techniques for the diagnosis and stratification of patients with prostate cancer. “We identified a set of biomarkers predictive for the genetic status in human prostate cancer patients, thus identifying potential responders to cancer therapies targeting specific pathways.”
In the initial discovery phase, Dr. Schiess and his group detected and identified N-linked glycoproteins with distinguishable expression patterns in primary normal and diseased tissue. “The proteins identified in the initial phase will be subjected to targeted MS analysis in plasma samples using highly sensitive and specific selected reaction-monitoring technology. Since glycosylated proteins, such as those secreted or shed from the cell surface, are likely to reside and persist in blood, the two-stage strategy is focused on the quantification of tissue-derived glycoproteins in plasma.”
Dr. Schiess noted that the focus on N-glycoproteome not only reduces the complexity of the analytes, but also targets an information-rich subproteome—relevant for remote sensing of diseases in the plasma. “The discovery and validation workflow allows for the robust identification of protein candidate panels that can be selectively monitored in blood plasma at high sensitivity in a reliable, noninvasive, and quantitative fashion.
“We further discovered serum biomarkers for the prognosis of localized prostate cancer providing additional noninvasive prognostic markers for cancer aggressiveness, and thereby, supporting the decision of active surveillance or immediate surgical intervention.”