123rd General Meeting of the KCS

Type Symposium
Area Analytical Technologies to Improve Human Health
Room No. Room 202
Time FRI 14:30-14:55
Code ANAL2-1
Subject Reference Proteome-Based Subtyping of Liver Cancer
Authors J. Eugene Lee
Center for Bioanalysis, Korea Research Institute of Standards and Science, Korea
Abstract Classification of hepatocellular carcinoma (HCC) into clinical subtypes is in high demand for the selection of proper treatment. For patients with HCC who are not or no longer candidates for locoregional therapy, oral multikinase inhibitors are the only established systemic alternative. Yet, the response rate of these FDA-approved drugs against HCC are less than one percent. Here, we adopted quantitative proteomic approaches in an attempt to characterize HCC subtypes in proteome level, and link these subtypes to drug response. We developed a liver reference proteome, a mixture of equal amounts of total proteins from seven liver cancer cell lines metabolically labeled with stable isotopes. This labeled reference proteome was utilized to cross-compare protein abundances from ten liver cancer cell lines that are widely used in research. Shotgun proteomic analysis on a hybrid quadrupole-orbitrap mass spectrometer with high mass accuracy at the MS and MS/MS levels yielded a liver proteome composed of 8,999 identified proteins, spanning 7 orders of magnitude in signal intensity. High-accuracy quantification allowed robust differentiation of HCC subtypes by principal component analysis. Furthermore, our liver reference proteome is being applied to quantify proteomes from liver cancer tissues collected from patients. HCC characterization by proteome expression may facilitate the establishment of clinical guidelines for subtype-specific systemic therapy.
E-mail j.eugenelee@gmail.com