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

机译:蛋白质组学和细胞因子血浆生物标志物,用于预测人类患者从大肠腺瘤到癌的进展

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摘要

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.
机译: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,以增进我们对CRC致瘤性和肿瘤进展的分子机制的了解。为此,我们使用2DE和MS的组合以及通过多重磁珠分析进行的差异调节细胞因子和趋化因子的分析,对血浆蛋白进行了蛋白质组学比较分析。蛋白质组学分析确定了11种上调的血浆蛋白和13种下调的血浆蛋白,它们显示出明显不同的调节模式,具有预测从腺瘤发展为癌的诊断潜力。这些蛋白质中的一些以前未曾涉及CRC,包括上调的富含亮氨酸的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,玻连蛋白和α-1-抗胰凝乳蛋白酶。此外,与腺瘤性息肉相比,CRC患者的三种细胞因子/趋化因子(包括白介素8,干扰素γ诱导的蛋白10和肿瘤坏死因子α)的血浆水平显着升高。尽管需要进一步的临床验证,但是这些蛋白质和细胞因子可以被确立为CRC和/或结肠腺瘤进展的新型生物标志物。

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