Loss of expression of the adipocyte-type fatty acid-binding protein (A-FABP) is associated with progression of human urothelial carcinomas

TY - JOUR

T1 - Loss of expression of the adipocyte-type fatty acid-binding protein (A-FABP) is associated with progression of human urothelial carcinomas

AU - Ohlsson, G.

AU - Gromov, P.

AU - Sauter, G.

AU - Celis, J.E.

AU - Moreira, José

PY - 2005

Y1 - 2005

N2 - 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 non-malignant 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 immuno-histochemical 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 γ (PPARγ), 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.

AB - 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 non-malignant 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 immuno-histochemical 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 γ (PPARγ), 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.

U2 - 10.1074/mcp.M500017-MCP200

DO - 10.1074/mcp.M500017-MCP200

M3 - Journal article

C2 - 15734831

AN - SCOPUS:17844396227

SN - 1535-9476

VL - 4

SP - 570

EP - 581

JO - Molecular and Cellular Proteomics

JF - Molecular and Cellular Proteomics

IS - 4

ER -