Rapid protein display profiling of cancer progression directly from human tissue using a protein biochip

The complicated, changing pattern of protein expression should contain impo rtant information about the pathologic process taking place in the cells of actual tissue. Utilization of this information for the selection of drugga ble targets could be possible if a means existed to rapidly analyze and dis play changes in protein expression in defined microscopic cellular subpopul ations. As a demonstration of feasibility, we show the generation of sensit ive, rapid, and reproducible molecular weight protein profiles of patient-m atched normal, premalignant, malignant, and metastatic microdissected cell populations from stained human esophageal, prostate, breast, ovary, colon, and hepatic tissue sections through the application of an affinity-based bi ochip. Reproducible, discriminatory protein biomarker profiles can be obtai ned from as few as 25 cells in less than 5 min from dissection to the gener ation of the protein fingerprint. Furthermore, these protein pattern profil es reveal reproducible changes in expression as cells undergo malignant tra nsformation, and are discriminatory for different tumor types. Consistent p rotein changes were identified in the microdissected cells from patient-mat ched tumor and normal epithelium from eight out of eight different malignan t esophageal tissue sets and three out of three malignant prostate tissue s ets. A means to rapidly generate a display of expressed proteins from micro scopic cellular populations sampled from tissue could be an important enabl ing technology for pharmacoproteomics, molecular pathology, drug interventi on strategies, therapeutic assessment of drug entities, disease diagnosis, toxicity, and gene therapy monitoring. Published 2000 Wiley-Liss, Inc.(+)