Proteomics Identification of Desmin as a Potential Oncofetal Diagnostic and Prognostic Biomarker in Colorectal Cancer

Proteomics Identification of Desmin as a Potential Oncofetal Diagnostic and Prognostic Biomarker in Colorectal Cancer
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DOI:
10.1074/mcp.m800541-mcp200
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发表时间:
2009-08-01
影响因子:
7
通讯作者:
Qin, Huanlong
Qin, Huanlong
中科院分区:
生物学1区
文献类型:
--
作者:
Ma, Yanlei;Peng, Jiayuan;Qin, Huanlong

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结直肠癌(CRC)是全球第三大常见癌症,预后较差。为了鉴定参与 CRC 癌变的癌胎儿蛋白,通过二维凝胶电泳和基于 MALDI-TOF/TOF 的蛋白质组学方法研究了胎儿结直肠组织、CRC 以及配对的肿瘤邻近正常结直肠组织之间的差异表达蛋白。这些组织中有42个差异表达的蛋白点,通过MS分析鉴定出22个蛋白。与正常结直肠组织相比,结蛋白和锌指蛋白 829 在 CRC 组织和胎儿结直肠组织中被发现升高。 RT-PCR和Western blot分析证实结蛋白在结直肠癌组织和胎儿结肠不同发育阶段的表达升高。免疫组织化学分析显示,desmin表达升高与CRC的严重程度和分化程度相关,并降低CRC患者的生存率。最后,通过开发一种高度灵敏的免疫测定法,可以在人血清中检测到结蛋白,并且与健康志愿者相比,结蛋白在结直肠癌患者中显着升高。我们建议将 desmin 视为 CRC 的潜在癌胎血清肿瘤标志物,可能对 CRC 患者的检测具有重要意义。分子与细胞蛋白质组学 8:1878-1890,2009。
Colorectal cancer (CRC) is the third most common cancer worldwide and has poor prognosis. To identify the oncofetal proteins involved in CRC carcinogenesis, differentially expressed proteins among fetal colorectal tissues, CRC, and the paired tumor-adjacent normal colorectal tissues were investigated by a two-dimensional gel electrophoresis and MALDI-TOF/TOF-based proteomics approach. 42 protein spots were differentially expressed among these tissues, and 22 proteins were identified by MS analysis. Desmin and zinc finger protein 829 were found to be elevated in CRC tissue and fetal colorectal tissue compared with normal colorectal tissue. The elevated expression of desmin in CRC tissue and different developmental stages of fetus colon was confirmed by RT-PCR and Western blot analysis. Immunohistochemical analysis showed that the elevated expression of desmin was correlated with the severity and differentiation of CRC and decreased survival rate of CRC patients. Finally by developing a highly sensitive immunoassay, desmin could be detected in human serum and was significantly elevated in CRC patients compared with healthy volunteers. We propose that desmin be considered a potential oncofetal serum tumor marker for CRC that may have significance in the detection of patients with CRC. Molecular & Cellular Proteomics 8: 1878-1890, 2009.