Organized proteomic heterogeneity in colorectal cancer liver metastases and implications for therapies

• DOI: 10.1002/hep.26608
• Publication Date: 2013-07-06T04:57:04Z
• Authors: Andrei Turtoi; Arnaud Blomme; Delphine Debois; Joan Somja; David Delvaux; Georgios Patsos; Emmanuel Di Valentin; Olivier Peulen; Eugène Nzaramba M...; Edwin De Pauw; Philippe Delvenne; Olivier Detry; Vincent Castronovo
• Keywords: Proteome; Liver Cancer

Tumor heterogeneity is a major obstacle for developing effective anticancer treatments. Recent studies have pointed to large stochastic genetic within cancer lesions, where no pattern seems exist that would enable more structured targeted therapy approach. Because date similar information available at the protein (phenotype) level, we employed matrix assisted laser desorption ionization (MALDI) image-guided proteomics and explored of extracellular membrane subproteome in unique collection eight fresh human colorectal carcinoma (CRC) liver metastases. Monitoring spatial distribution over 1,000 proteins, found unexpectedly all metastasis lesions displayed reproducible, zonally delineated functional therapeutic biomarker heterogeneity. The peritumoral region featured elevated lipid metabolism synthesis, rim increased cellular growth, movement, drug metabolism, whereas center lesion was characterized by carbohydrate DNA-repair activity. From aspect targeting, zonal expression known novel biomarkers evident, reinforcing need select several targets order achieve optimal coverage lesion. Finally, highlight two antigens, LTBP2 TGFBI, whose consistent feature CRC metastasis. We demonstrate their vivo antibody-based targeting potential usefulness clinical applications.The proteome metastases has distinct, organized pattern. This particular hallmark can now be used as part strategy rational therapies based on multiple sets targetable antigens.