title: Loss of expression of the adipocyte-type fatty acid-binding protein (A-FABP) is associated with progression of human urothelial carcinomas.
abstract: Bladder cancer is the fifth most common malignancy in the world and represents the second most common cause of death among genitourinary tumors. Current prognostic parameters such as grade and stage cannot predict with certainty the long-term outcome of bladder cancer, and as a result there is a pressing need to identify markers that may predict tumor behavior. Earlier we identified the adipocyte fatty acid-binding protein (A-FABP), a small-molecular-mass fatty acid-binding protein that functions by facilitating the intracellular diffusion of fatty acids between cellular compartments as a putative marker of progression based on a limited study of fresh bladder urothelial carcinomas (UCs) (Celis, J. E., Ostergaard, M., Basse, B., Celis, A., Lauridsen, J. B., Ratz, G. P., Andersen, I., Hein, B., Wolf, H., Orntoft, T. F., and Rasmussen, H. H. (1996) Loss of adipocyte-type fatty acid binding protein and other protein biomarkers is associated with progression of human bladder transitional cell carcinomas. Cancer Res.56, 4782-4790). Here we have comprehensively examined the protein expression profiles of a much larger sample set consisting of 153 bladder specimens (46 nonmalignant biopsies, 11 pTa G1, 40 pTa G2, 10 pTa G3, 13 pT1 G3, 23 pT2-4 G3, and 10 pT2-4 G4) by gel-based proteomics in combination with immunohistochemistry (IHC) using a peptide-based rabbit polyclonal antibody that reacts specifically with this protein. Proteomic profiling showed a striking down-regulation of A-FABP in invasive lesions, a fact that correlated well with immunohistochemical analysis of the same samples. The IHC results were confirmed by using a tissue microarray (TMA) containing 2,317 samples derived from 1,849 bladder cancer patients. Moreover, we found that the altered expression of A-FABP in invasive UCs is not due to deregulated expression of peroxisome proliferator-activated receptor gamma (PPARgamma), a trans-activator of A-FABP. Taken together, these results provide evidence that deregulation of A-FABP may play a role in bladder cancer progression and suggest that A-FABP could have a significant prognostic value in combination with other biomarkers.
authors.affiliation: Department of Proteomics in Cancer, Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark DK-2100, USA. gio@cancer.dk
authors.forename: Gita
authors.initials: G
authors.lastname: Ohlsson
authors.forename: José M A
authors.initials: JM
authors.lastname: Moreira
authors.forename: Pavel
authors.initials: P
authors.lastname: Gromov
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Julio E
authors.initials: JE
authors.lastname: Celis
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D015153:Blotting, Western; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D002352:Carrier Proteins / Q000378:metabolism*; D018450:Disease Progression; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D050556:Fatty Acid-Binding Proteins; D019084:Fluorescent Antibody Technique, Indirect; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D020411:Oligonucleotide Array Sequence Analysis; D020543:Proteome / Q000032:analysis; D040901:Proteomics / Q000379:methods; D012189:Retrospective Studies; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D050556:Fatty Acid-Binding Proteins; D020543:Proteome