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用于预测人类患者从结直肠腺瘤进展为癌的蛋白质组学和细胞因子血浆生物标志物。

Proteomic and cytokine plasma biomarkers for predicting progression from colorectal adenoma to carcinoma in human patients.

机构信息

Department of Biotechnology, Daegu University, Kyungsan, Republic of Korea.

出版信息

Proteomics. 2013 Aug;13(15):2361-74. doi: 10.1002/pmic.201200550. Epub 2013 Jun 18.

Abstract

In the present study, we screened proteomic and cytokine biomarkers between patients with adenomatous polyps and colorectal cancer (CRC) in order to improve our understanding of the molecular mechanisms behind turmorigenesis and tumor progression in CRC. To this end, we performed comparative proteomic analysis of plasma proteins using a combination of 2DE and MS as well as profiled differentially regulated cytokines and chemokines by multiplex bead analysis. Proteomic analysis identified 11 upregulated and 13 downregulated plasma proteins showing significantly different regulation patterns with diagnostic potential for predicting progression from adenoma to carcinoma. Some of these proteins have not previously been implicated in CRC, including upregulated leucine-rich α-2-glycoprotein, hemoglobin subunit β, Ig α-2 chain C region, and complement factor B as well as downregulated afamin, zinc-α-2-glycoprotein, vitronectin, and α-1-antichymotrypsin. In addition, plasma levels of three cytokines/chemokines, including interleukin-8, interferon gamma-induced protein 10, and tumor necrosis factor α, were remarkably elevated in patients with CRC compared to those with adenomatous polyps. Although further clinical validation is required, these proteins and cytokines can be established as novel biomarkers for CRC and/or its progression from colon adenoma.

摘要

在本研究中,我们筛选了腺瘤性息肉和结直肠癌(CRC)患者之间的蛋白质组学和细胞因子生物标志物,以加深我们对 CRC 肿瘤发生和肿瘤进展背后分子机制的理解。为此,我们使用 2DE 和 MS 组合进行了血浆蛋白的比较蛋白质组学分析,并通过多重珠分析对差异调节的细胞因子和趋化因子进行了分析。蛋白质组学分析鉴定出 11 种上调和 13 种下调的血浆蛋白,这些蛋白具有不同的调节模式,具有预测从腺瘤进展为癌的诊断潜力。其中一些蛋白质以前未涉及 CRC,包括上调的亮氨酸丰富的α-2-糖蛋白、血红蛋白亚基β、Igα-2 链 C 区和补体因子 B 以及下调的 afamin、锌-α-2-糖蛋白、纤连蛋白和α-1-抗糜蛋白酶。此外,与腺瘤性息肉患者相比,CRC 患者血浆中三种细胞因子/趋化因子(包括白细胞介素 8、干扰素γ诱导蛋白 10 和肿瘤坏死因子α)的水平显著升高。尽管需要进一步的临床验证,但这些蛋白质和细胞因子可以作为 CRC 及其从结肠腺瘤进展的新型生物标志物。

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