摘要

PURPOSE:The goal of this study was to identify and validate novel serum markers of human colorectal cancer as potential candidates for noninvasive detection of early colorectal neoplasm.
EXPERIMENTAL DESIGN:Employing two-dimensional gel electrophoresis and mass spectrometry, we analyzed 16 matched colorectal cancer and adjacent normal tissue samples. Proteins found to be elevated in cancer tissue were further validated by generating antibodies which were used for immunoblotting of tissue samples and for the development of highly sensitive immunoassays for assessment of serum samples.
RESULTS:In total, 735 different proteins were identified in colon tissue. Strong elevation in colorectal cancer for five proteins was confirmed by immunoblot analysis: transforming growth factor-beta induced protein ig-h3 (betaIG-H3), nicotinamide N-methyltransferase (NNMT), nucleoside diphosphate kinase A (nm23-H1), purine nucleoside phosphorylase (PNPH), and mannose-6-phosphate receptor binding protein 1 (M6P1). Elevated levels of NNMT, which is not predicted to be secreted but is known as a cytoplasmic protein, were found in serum from patients with colorectal cancer. Employing a receiver-operating characteristic curve based on the measurement of 109 patients with colorectal cancer and 317 healthy controls, we obtained an area under the curve of 0.84 for NNMT, which was superior to the established tumor marker carcinoembryogenic antigen with an area under the curve of 0.78.
CONCLUSIONS:It is proposed that NNMT serum levels may have significance in the early detection and in the management of patients with colorectal cancer.

译文

目的: 本研究的目的是鉴定和验证人类结直肠癌的新型血清标志物,作为无创检测早期结直肠癌的潜在候选物。
实验设计: 采用双向凝胶电泳和质谱分析法,我们分析了 16 个匹配的结直肠癌和癌旁正常组织样本。发现在癌症组织中被提升的蛋白质通过产生抗体被进一步验证,这些抗体被用于组织样本的免疫印迹和用于评估血清样本的高灵敏度免疫试验的发展。
结果: 在结肠组织中总共发现了 735 种不同的蛋白质。通过免疫印迹分析证实了五种蛋白质在结直肠癌中的强烈升高: 转化生长因子-β 诱导蛋白 ig-h3 (betaIG-H3),烟酰胺 N-甲基转移酶 (NNMT), 核苷二磷酸激酶 A (nm23-H1) 、嘌呤核苷磷酸化酶 (PNPH) 和 mannose-6-phosphate 受体结合蛋白 1 (M6P1)。在结直肠癌患者的血清中发现了 NNMT 水平升高,该水平预计不会分泌,但被称为细胞质蛋白。基于对 109 名结直肠癌患者和 317 名健康对照组的测量,采用受试者工作特征曲线,我们获得了 NNMT 曲线下 0.84 的面积, 其优于已建立的肿瘤标记物癌胚抗原,曲线下面积为 0.78。
结论: NNMT 血清水平可能在结直肠癌患者的早期发现和管理中具有意义。

Nicotinamide N-Methyltransferase

肿瘤 甲基化酶 临床研究术语
概述  :  

烟酰胺N-甲基转移酶(NNMT)是由NNMT基因编码的,人体内重要的甲基化酶;该酶是一种S-腺苷-L-蛋氨酸(SAM)依赖性胞质酶,在多种药物以及异型物质的生物转化和解毒中起重要作用,参与这些物质在体内的生物转化。现有研究显示烟酰胺N-甲基转移酶在肥胖和糖尿病代谢相关疾病中发挥重要作用,同时该酶在多种肿瘤中也出现异常表达,可能与肿瘤的发生、发展以及放疗抵抗等密切相关。生物学特征上世纪90年代,Aksoy等最早应用cDNA克隆技术在人肝组织中鉴定出了烟酰胺N-甲基转移酶基因,发现其位于11号染

Nicotinamide   英 /,nɪkə'tɪnəmaɪd/   美 /,nɪkə'tɪnəmɪd/ 

释    义   n. [生化] 烟酰胺;烟碱;尼克酰胺

例   句   He used nicotinamide to tranquilize the animal.  他用烟酰胺使动物镇静。


Methyltransferase   /,meθil'trænsfəreis/

释    义   n. [生化] 甲基转移酶

例    句   DNA production independent of its methyltransferase activity.  DNA生产独立于其甲基转移酶活性。

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