Proteins That Underlie Neoplastic Progression of Ulcerative Colitis.
Proteins That Underlie Neoplastic Progression of Ulcerative Colitis.
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DOI：
10.1002/prca.200900061
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发表时间：
2009-09-14
影响因子：
2
通讯作者：
Chen, Ru
中科院分区：
文献类型：
--
作者：
Brentnall, Teresa A.;Pan, Sheng;Bronner, Mary P.;Crispin, David A.;Mirzaei, Hamid;Cooke, Kelly;Tamura, Yasuko;Nikolskaya, Tatiana;JeBailey, Lellean;Goodlett, David R.;McIntosh, Martin;Aebersold, Ruedi;Rabinovitch, Peter S.;Chen, Ru
溃疡性结肠炎（UC）患者患结直肠癌的风险增加。因为 UC 肿瘤发生与基因组缺陷有关，这些缺陷可以延伸到整个结肠，包括非发育不良的粘膜；我们假设相同的场缺陷将包括异常表达的蛋白质。在这里，我们应用蛋白质组学来研究 UC 肿瘤进展的蛋白质表达。比较 1) 无发育不良的 UC 患者（非进展者）的结肠上皮蛋白质谱； 2)来自患有高度不典型增生或癌症的UC患者（进展者）的非不典型增生结肠组织； 3) 来自 UC 进展者的高度发育不良组织和 4) 正常结肠。我们鉴定了与 UC 肿瘤进展相关的蛋白质差异表达。与线粒体、氧化活性、钙结合蛋白相关的蛋白质是这些蛋白质中一些有趣的类别。网络分析发现，Sp1 和 c-myc 蛋白可能分别在 UC 肿瘤进展的早期和晚期阶段发挥作用。 IHC 分析进一步证实了 UC 进展者非发育不良组织中两种过度表达的蛋白 CPS1 和 S100P。我们的研究深入了解了与 UC 肿瘤进展相关的分子事件，可用于开发非发育不良粘膜领域的蛋白质生物标志物，以识别患者患 UC 发育不良的风险。
Patients with ulcerative colitis (UC) have an increased risk for developing colorectal cancer. Because UC tumorigenesis is associated with genomic field defects that can extend throughout the entire colon, including the non-dysplastic mucosa; we hypothesized that the same field defect will include abnormally expressed proteins. Here we applied proteomics to study the protein expression of UC neoplastic progression. The protein profiles of colonic epithelium were compared from 1) UC patients without dysplasia (non-progressors); 2) none-dysplastic colonic tissue from UC patient with high-grade dysplasia or cancer (progressors); 3) high-grade dysplastic tissue from UC progressors and 4) normal colon. We identified protein differential expression associated with UC neoplastic progression. Proteins relating to mitochondria, oxidative activity, calcium-binding proteins were some of interesting classes of these proteins. Network analysis discovered that Sp1 and c-myc proteins may play roles in UC early and late stages of neoplastic progression, respectively. Two over-expressed proteins in the non-dysplastic tissue of UC progressors, CPS1 and S100P, were further confirmed by IHC analysis. Our study provides insight into the molecular events associated with UC neoplastic progression, which could be exploited for the development of protein biomarkers in fields of non-dysplastic mucosa that identify a patient’s risk for UC dysplasia.
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影响因子：
13.5
作者：
Kinoshita, M;Miyata, M
通讯作者：
Miyata, M
影响因子：
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作者：
MACPHERSON, AJS;CHESTER, KA;PETERS, TJ
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影响因子：
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作者：
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通讯作者：
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影响因子：
3.4
作者：
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通讯作者：
Lee, Ying-Shiung