Department of Ocular Pathology, Vision Research Foundation, Sankara Nethralaya, Chennai, India.
Proteomics Clin Appl. 2010 Apr;4(4):449-63. doi: 10.1002/prca.200900069. Epub 2010 Jan 4.
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.
2-DE and MALDI-TOF-TOF MS/MS were used to identify differentially expressed proteins.
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).
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.
为了了解疾病的机制，并确定潜在的肿瘤标志物，以帮助治疗，我们对 29 例视网膜母细胞瘤（RB）肿瘤进行了比较蛋白质组学分析，使用 14 例非肿瘤性视网膜（年龄在 45 岁至 89 岁之间）作为对照组织。
使用 2-DE 和 MALDI-TOF-TOF MS/MS 来鉴定差异表达的蛋白质。
鉴定出 27 种明显差异表达的蛋白质，包括 16 种上调和 11 种下调的蛋白质。值得注意的是，与正常视网膜相比，RB 中的载脂蛋白 A1（apolipoprotein A1，ApoA1；p<0.001）、转铁蛋白（transferrin，TF；p<0.001）、细胞视黄醇结合蛋白 2（cellular retinol binding protein 2，CRABP2；p<0.001）和α-晶状体蛋白 A（α-crystallin A，CRYAA；p<0.001）的 mRNA 水平明显升高，与蛋白质组学数据一致。还对石蜡 RB 块上的选定蛋白质进行了免疫组织化学染色，以确认蛋白质表达。有侵袭性的 RB 通过 CRABP2（p<0.001）、过氧化物还原酶 6（peroxiredoxin 6，PRDX6；p=0.025）、载脂蛋白 A1（p<0.001）和恢复蛋白（recoverin，p<0.001）的 2-DE-MS/MS 分析显示出显著更高的表达。
因此，本研究提供了 RB 肿瘤的动态蛋白质谱，这可能为研究 RB 致癌机制提供线索，并可能作为预后和治疗的潜在生物标志物。
