Identification of nicotinamide N-methyltransferase as a novel serum tumor marker for colorectal cancer
Identification of nicotinamide N-methyltransferase as a novel serum tumor marker for colorectal cancer
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DOI：
10.1158/1078-0432.ccr-05-0983
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发表时间：
2005-09-15
影响因子：
11.5
通讯作者：
Tacke, M
中科院分区：
文献类型：
--
作者：
Roessler, M;Rollinger, W;Tacke, M
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，作为早期结直肠癌无创检测的潜在候选物。实验设计：采用双向凝胶电泳和质谱技术，对16例匹配的结直肠癌和邻近正常组织样本进行分析。蛋白质被发现。通过产生用于组织样本免疫印迹和开发用于评估血清样本的高灵敏度免疫测定的抗体，进一步验证了癌症组织中Be的升高。结果:。在结肠组织中共鉴定出735种不同的蛋白质。免疫印迹分析证实，生长因子β诱导蛋白ig-h3 -(β ig-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）和甘露糖-6-磷酸受体结合蛋白1 （M6P1）对结直肠癌的转化有明显的促进作用。在结直肠癌患者的血清中发现了NNMT水平升高，NNMT是一种细胞质蛋白，预计不会分泌。1 .通过对109例结直肠癌患者和317例健康对照者的测量，我们得到了NNMT的曲线下面积为0.84，优于已建立的肿瘤标志物。致癌胚胎发生抗原，曲线下面积为0.78。结论：血清NNMT水平对结直肠癌患者的早期发现和治疗可能具有重要意义。
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 identifed in colon, tissue. Strong elevation in immunoblot analysis transforming, colorectal cancer for five proteins was confirmed by in growth factor-beta induced protein ig-h3 -(beta iG-H3) nicotinamide N-methyltransferase (NNMT), nucleoside, diphosphate kinase A (nm23-H1), purine nucleioside 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 proteins were found in serum from patients with colorectal cancer. I 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. carcinoembryogeniec antigon 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.