Identification and confirmation of increased fibrinopeptide A serum protein levels in gastric cancer sera by magnet bead assisted MALDI-TOF mass spectrometry

Identification and confirmation of increased fibrinopeptide A serum protein levels in gastric cancer sera by magnet bead assisted MALDI-TOF mass spectrometry
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DOI:
10.1021/pr060011c
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发表时间:
2006-09-01
影响因子:
4.4
通讯作者:
Rocken, Christoph
Rocken, Christoph
中科院分区:
生物学2区
文献类型:
--
作者:
Ebert, Matthias P. A.;Niemeyer, Dagmar;Rocken, Christoph

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胃癌是第二常见的恶性肿瘤,预后仍然很差。预后不良的原因是缺乏敏感的血清标志物来早期发现和筛查高危个体,以及癌症晚期的治疗选择有限。采用MALDI-TOF质谱法对14例胃癌患者和14例健康对照者的血清进行磁疏水C8包被珠预分离后,生成质谱。为了证实胃癌血清的蛋白质组学分析,我们筛选了更多的胃癌患者(n = 99)、高危人群(n = 13)和正常对照(n = 111)的血清纤维蛋白肽A水平。有趣的是,与正常对照(平均3.303 +/- 0.4012)相比,癌症患者(平均3.636 +/- 0.3738;p < 0.0001)和高危人群(平均3.569 +/- 0.4722;p < 0.05)的血清纤维蛋白肽A水平的平均对数浓度显著更高。相反,我们观察到纤维蛋白肽A水平与肿瘤分期、肿瘤位置、是否存在局部或远处转移以及胃癌的劳伦类型无关。总之,预分离胃癌血清的MALDI-TOF质谱法可以识别潜在的生物标志物,这可能导致基于血清的筛查高风险个体的测试的发展。
Gastric cancer is the second most common malignancy and prognosis remains dismal. The reasons for the poor prognosis are the lack of sensitive serum markers for early detection and screening of high-risk individuals as well as the limited treatment options in advanced cancer stages. Using MALDI-TOF mass spectrometry after prefractionation of sera with magnet hydrophobic C8 coated beads sera from 14 patients with gastric cancer and 14 healthy controls mass spectra were generated. A peptide fragment was found to be highly elevated in cancer sera and was identified as fibrinopeptide A. To confirm proteome analysis of gastric cancer sera, we then screened a larger series of patients with gastric cancer (n = 99), high-risk individuals (n = 13) and normal controls (n = 111) for fibrinopeptide A serum levels. Interestingly, the mean logarithmic concentrations of serum fibrinopeptide A levels were significantly higher in cancer patients (mean 3.636 +/- 0.3738; p < 0.0001) and high-risk individuals (mean 3.569 +/- 0.4722; p < 0.05) compared to normal controls (mean 3.303 +/- 0.4012). In contrast, we observed no association of fibrinopeptide A levels with tumor stage, tumor location, presence of regional or distant metastasis, and Lauren type of gastric cancer. In conclusion, MALDI-TOF mass spectrometry of prefractionated gastric cancer sera allows the identification of potential biomarkers that may lead to the development of serum based tests for screening of high-risk individuals.