Comparative Proteomics of Retinoblastoma Reveals Cellular Retinoic AcidBinding Protein (CRABP) I and II as Potential Targets

Abstract

Purpose: : To understand the disease mechanism and to investigate the potential tumor markers that would help in therapeutics, comparative proteomic analysis of retinoblastoma was performed.

Methods: : The total protein samples of the donor retina ( controls) and tumor was subjected to two dimensional gel electrophoresis (2DE) and the differential proteins were identified by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry (MALDI-TOF-TOF). Real time quantitative PCR was performed to validate the proteomic data. Immunohistochemistry was performed for highly upregulated proteins on retinoblastoma paraffin Sections

Results: : There was 23 distinct, differentially expressed proteins in tumor samples in comparison with normal retina, belonging to various functional groups such as energy metabolism enzymes, transport proteins, cytoskeleton,chaperons, and regulatory proteins. Interestingly, Cellular retinoic acid binding protein II (CRABP-II), Apolipoprotein A1 (Apo A1) were highly upregulated in retinoblastoma. In contrary, CRABP-I was significantly downregulated in retinoblastoma compared to normal retina. The results of real time PCR quantification were consistent with the proteomics data. We observed strong cytoplasmic positivity for CRABPII and Apolipoprotein A1 in tumor cells

Conclusions: : Interestingly, CRABP-II and CRABP-I are differentially regulated in retinoblastoma and epigenetics has been shown to be the cause for differential regulation by earlier studies in various cancers. Our findings suggest that CRABP-II and CRABP-I may be potential therapeutic targets for retinoblastoma.

Keywords: retinoblastoma • proteomics • tumors