Proteomic Studies of Anaplasia in Wilms Tumor

Wilms tumor is the most common malignant tumor in the pediatric kidney. Anaplasia, focal or diffuse as defined by histological criteria, is the most important parameter to guide the clinical treatment plan. We sought to identify and characterize potential useful biomarkers associated with anaplasia and provide insight into the peculiar molecular biology of Wilms tumor with unfavorable histology.

Utilizing isobaric tagging technology for relative and absolute quantitation, coupled with tandem mass spectrometry, we identified proteins that are differently regulated in different Wilms tumor histologies. Four Wilms tumor specimens were selected, including two with classic favorable histology, one with focal anaplasia, and one with diffuse anaplasia. A total of 256 proteins with a Protein Score >1.0 are identified from all samples (proteins with >90% confidence).

Compared with classic favorable morphology: in the focal anaplasia group, we identified a total of 26 proteins of which six were underexpressed and 20 were overexpressed; in the diffuse anaplasia group, we identified a total of 20 proteins of which eight were underexpressed and 12 were overexpressed. With a total of 39 involved proteins, seven were common to both the focal and diffuse anaplasia cases, and clearly seemed to have a similar regulation. The newly identified potential markers for Wilms tumor with unfavorable histology include ENO1, GAPDH, ALDOA, SLC25A6, LDHA, PGAM1, MIF, RBP1, HBA, HP, COL1A1, CFL1, and FSCN1 etc.

In Wilms tumors, though there are unfavorable histology differences (focal or diffuse anaplasia), the protein expression seems to be similarly dysregulated compared with the favorable histology group. The newly identified potential markers may provide insights into the molecular biology of Wilms tumor and may have practical implications.