Comparative proteomic analysis of differentially expressed proteins in primary retinoblastoma tumors

• Published in: Proteomics. Clinical applications Vol. 4; no. 4; pp. 449 - 463
• Main Authors: Mallikarjuna, Kandalam, Sundaram, Curam Sreenivasacharlu, Sharma, Yogendra, Deepa, Perinkulam Ravi, Khetan, Vikas, Gopal, Lingam, Biswas, Jyotirmay, Sharma, Tarun, Krishnakumar, Subramanian
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01-04-2010; WILEY‐VCH Verlag; Wiley
• Subjects: Aged; Aged, 80 and over; Biological and medical sciences; Biomarkers, Tumor - blood; Differential expression; Diverse techniques; Electrophoresis, Gel, Two-Dimensional; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Male; Medical sciences; Middle Aged; Molecular and cellular biology; Ophthalmology; Proteomics; Retina; Retinoblastoma; Retinoblastoma - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tumors and pseudotumors of the eye, orbit, eyelid, lacrimal apparatus; Analysis; Proteomics; Retina; Tumor; Gene expression; Retinoblastoma; Differential expression; Protein
• ISSN: 1862-8346; 1862-8354
• DOI: 10.1002/prca.200900069

Purpose: To understand the disease mechanism and to identify the potential tumor markers that would help in therapeutics, comparative proteomic analysis of 29 retinoblastoma (RB) tumors was performed using 14 non‐neoplastic retinas (age ranged from 45 to 89 years) as control tissues.
Experimental design: 2‐DE and MALDI‐TOF‐TOF MS/MS were used to identify differentially expressed proteins.
Results: Twenty‐seven distinct differentially expressed proteins were identified, including 16 upregulated 11 downregulated proteins. Significantly, higher mRNA levels of apolipoprotein A1 (p<0.001), transferrin (TF; p<0.001), CRABP2 (p<0.001), α‐crystallin A (CRYAA; p<0.001) were observed in RBs when compared with normal retinas and hence are consistent with the proteomic data. Immunohistochemistry was also performed for selected proteins on paraffin RB blocks to confirm protein expression. RB with invasion showed significantly higher expression by 2‐DE‐MS/MS analysis of CRABP2 (p<0.001), peroxiredoxin 6 (p=0.025), apolipoprotein A1 (p<0.001), recoverin (p<0.001).
Conclusions and clinical relevance: Thus, this study provides a dynamic protein profile of RB tumors, which could provide clues to study the mechanisms of RB oncogenesis and possibly be developed as potential biomarkers for prognosis and therapy.