Analysis of MALDI-TOF mass spectrometry data for discovery of peptide and glycan biomarkers of hepatocellular carcinoma
Analysis of MALDI-TOF mass spectrometry data for discovery of peptide and glycan biomarkers of hepatocellular carcinoma
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DOI：
10.1021/pr0705237
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发表时间：
2008-02-01
影响因子：
4.4
通讯作者：
Goldman, Radoslav
中科院分区：
文献类型：
--
作者：
Ressom, Habtorn W.;Varghese, Rency S.;Goldman, Radoslav
本文提出了分析 MALDI-TOF 质谱数据的计算方法，以定量比较血清中的肽和聚糖。该方法用于鉴定 203 名埃及参与者血清样本中的候选生物标志物； 73 例肝细胞癌 (HCC) 病例、52 例慢性肝病 (CLD) 患者（包括肝硬化和纤维化病例）以及 78 例人群对照。在生成质谱之前应用两种互补的样品制备方法：(1) 对每个血清样品进行低分子量 (LMW) 富集，以进行肽的 MALDI-TOF 定量；(2) 从每个血清样品中的蛋白质中酶促释放聚糖，并进行全甲基化，以进行聚糖的 MALDI-TOF 定量。应用峰选择算法来识别最有用的肽和聚糖峰，以准确检测来自 CLD 高危人群的 HCC 病例。除了通过基于整个群体的方法选择的全局峰（其中相同标记的患者被视为单个组）之外，通过搜索仅在患者亚组中丰度存在差异的峰来识别亚组特异性峰。峰选择过程之前是峰筛选，我们根据群体对照的肽和聚糖光谱消除了与年龄、性别和病毒感染等协变量显着相关的峰。所选肽和聚糖峰的性能根据其在盲法验证集中和交叉验证方法中检测 CLD 患者 HCC 病例的能力进行了评估。最后，我们研究了在一组中使用肽和聚糖以增强这些候选标记物的诊断能力的可能性。需要进一步评估以检查本研究中确定的候选肽和聚糖标记物的潜在临床效用。
This paper presents computational methods to analyze MALDI-TOF mass spectrometry data for quantitative comparison of peptides and glycans in serum. The methods are applied to identify candidate biomarkers in serum samples of 203 participants from Egypt; 73 hepatocellular carcinoma (HCC) cases, 52 patients with chronic liver disease (CLD) consisting of cirrhosis and fibrosis cases, and 78 population controls. Two complementary sample preparation methods were applied prior to generating mass spectra: (1) low molecular weight (LMW) enrichment of each serum sample was carried out for MALDI-TOF quantification of peptides, and (2) glycans were enzymatically released from proteins in each serum sample and permethylated for MALDI-TOF quantification of glycans. A peak selection algorithm was applied to identify the most useful peptide and glycan peaks for accurate detection of HCC cases from high-risk population of patients with CLD. In addition to global peaks selected by the whole population based approach, where identically labeled patients are treated as a single group, subgroup-specific peaks were identified by searching for peaks that are differentially abundant in a subgroup of patients only. The peak selection process was preceded by peak screening, where we eliminated peaks that have significant association with covariates such as age, gender, and viral infection based on the peptide and glycan spectra from population controls. The performance of the selected peptide and glycan peaks was evaluated in terms of their ability in detecting HCC cases from patients with CLD in a blinded validation set and through the cross-validation method. Finally, we investigated the possibility of using both peptides and glycans in a panel to enhance the diagnostic capability of these candidate markers. Further evaluation is needed to examine the potential clinical utility of the candidate peptide and glycan markers identified in this study.