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首页> 外文期刊>Acta biochimica Polonica >Pre-analytical-related variability influencing serum peptide profiles demonstrated in a mass spectrometry-based search for colorectal and prostate cancer biomarkers
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Pre-analytical-related variability influencing serum peptide profiles demonstrated in a mass spectrometry-based search for colorectal and prostate cancer biomarkers

机译：在基于质谱的大肠癌和前列腺癌生物标志物检索中证实了影响血清肽谱的分析前相关变异性

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Although the degradome, which comprises proteolytic fragments of blood proteins, presents a potential source of diagnostic biomarkers, studies on cancer peptide biomarkers have provided inconsistent conclusions. In the present study, we reevaluated the usefulness of serum degradome analyses for searching peptide cancer biomarker candidates. Particular attention was paid to pre-analytical factors influencing the variability of determined peptide levels, including clotting time and control group selection. Studies were conducted on 44 and 86 serum samples collected from cancer patients and healthy individuals, respectively, using liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS)-based analyses. We identified 1373 unique peptides, nearly 40% of which originated from five blood proteins: fibrinogen alpha chain, apolipoprotein A-IV (APOA4), complement C3, apolipoprotein A-I, and alpha-1-antitrypsin. A set of 118 and 88 peptides exhibited highly significant differences (adjusted p -value ≤ 0.01 and fold change ≥ 2) in pair-wise comparisons of control vs. prostate cancer and control vs . colorectal cancer, respectively, with 37 peptides displaying a consistent direction of change for these pair-wise comparisons. The levels of 67 peptides differed significantly in serum samples collected from healthy individuals immediately prior to colonoscopy and those who underwent colonoscopic examination at least four weeks earlier. Of them, 49 peptides originated from APOA4. Whereas earlier studies, including ours, have utilized fragments of fibrinopeptide A (FPA) to distinguish cancer from healthy cases, here we show that their absolute abundance is a sensitive indicator of clotting time. These observations may have implications for future serum peptidome studies since these issues have not previously been recognized.
机译：尽管包含血液蛋白蛋白水解片段的降解组提供了诊断生物标志物的潜在来源，但是对癌肽生物标志物的研究却得出了不一致的结论。在本研究中，我们重新评估了血清降解组分析对寻找肽癌生物标志物候选物的有用性。特别注意影响确定肽段水平变异性的分析前因素，包括凝血时间和对照组选择。使用基于液相色谱电喷雾电离质谱（LC-ESI-MS）的分析，分别对从癌症患者和健康个体收集的44和86个血清样本进行了研究。我们鉴定了1373个独特的肽，其中近40％来自五个血液蛋白：纤维蛋白原α链，载脂蛋白A-IV（APOA4），补体C3，载脂蛋白A-I和alpha-1-抗胰蛋白酶。在对照与前列腺癌和对照与前列腺癌的成对比较中，一组118和88个肽表现出极显着的差异（调整后的p值≤0.01，倍数变化≥2）。对于这些成对比较，分别具有37个肽段的大肠癌表现出一致的变化方向。在从刚进行结肠镜检查之前的健康个体和至少在四周前接受结肠镜检查的人的血清样本中，67种肽的水平差异显着。其中，有49种肽源于APOA4。尽管包括我们在内的早期研究已利用纤维蛋白肽A（FPA）片段将癌症与健康病例区分开来，但在这里我们表明它们的绝对丰度是凝血时间的敏感指标。这些观察结果可能对未来的血清肽组研究产生影响，因为这些问题以前尚未被认识到。

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