Enzymes, which play an important role in cellular homeostasis, are a group of proteins essential for vital activities such as digestion, absorption, and metabolism. Technologies to detect and analyze aberrant enzyme activities in relation to a specified disease in the blood are useful for the disease diagnosis. However, current technologies that use spectroscopic methods treat the protein molecules as a group of 106-109 molecules, and development of more sensitive methodologies are desired to develop a novel biomarker of pancreatic cancer, which is difficult to diagnose at an early stage.
A research group led by Assistant Professor Toru Komatsu of the Graduate School of Pharmaceutical Sciences at the University of Tokyo has established a methodology of detecting various proteases at the single-molecule level by combining fluorescent probe technology, which detects specific enzyme activities by fluorescent signals, with microdevice-based high-precision measurement technology. This methodology enabled the detection of enzyme activity in blood at ultra-high sensitivity and was able to detect the weaker enzyme activities that were hardly detectable in the conventional methodology.
Using this methodology, the research group analyzed plasma samples from patients with early-stage pancreatic cancer and found differences in single-molecule level activities of enzymes, such as DPP4, elastase, and CD13, from those of healthy controls. These abnormalities were confirmed by measurement using different sets of samples under blind conditions.
Pancreatic cancer is one of the cancers with the lowest five-year survival rate due to the difficulty of early detection. Currently, social implementation research for practical use of the methodology is ongoing. In addition, the extended research is led by the research group to discover further single-molecule enzyme activity biomarkers.
Courtesy of the University of Tokyo, RIKEN, and Nippon Medical School