Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany.
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Int J Mol Sci. 2021 Jan 26;22(3):1189. doi: 10.3390/ijms22031189.
Blood-based protein biomarkers are increasingly being explored as supplementary or efficient alternatives for population-based screening of colorectal cancer (CRC). The objective of the current study was to compare the diagnostic potential of proteins measured with different proteomic technologies. The concentrations of protein biomarkers were measured using proximity extension assays (PEAs), liquid chromatography/multiple reaction monitoring-mass spectrometry (LC/MRM-MS) and quantibody microarrays (QMAs) in plasma samples of 56 CRC patients and 99 participants free of neoplasms. In another approach, proteins were measured in serum samples of 30 CRC cases and 30 participants free of neoplasm using immunome full-length functional protein arrays (IpAs). From all the measurements, 9, 6, 35 and 14 protein biomarkers overlapped for comparative evaluation of (a) PEA and LC/MRM-MS, (b) PEA and QMA, (c) PEA and IpA, and (d) LC/MRM-MS and IpA measurements, respectively. Correlation analysis was performed, along with calculation of the area under the curve (AUC) for assessing the diagnostic potential of each biomarker. DeLong's test was performed to assess the differences in AUC. Evaluation of the nine biomarkers measured with PEA and LC/MRM-MS displayed correlation coefficients >+0.6, similar AUCs and DeLong's -values indicating no differences in AUCs for biomarkers like insulin-like growth factor binding protein 2 (IGFBP2), matrix metalloproteinase 9 (MMP9) and serum paraoxonase lactonase 3 (PON3). Comparing six proteins measured with PEA and QMA showed good correlation and similar diagnostic performance for only one protein, growth differentiation factor 15 (GDF15). The comparison of 35 proteins measured with IpA and PEA and 14 proteins analyzed with IpA and LC/MRM-MS revealed poor concordance and comparatively better AUCs when measured with PEA and LC/MRM-MS. The comparison of different proteomic technologies suggests the superior performance of novel technologies like PEA and LC/MRM-MS over the assessed array-based technologies in blood-protein-based early detection of CRC.
基于血液的蛋白质生物标志物正被越来越多地探索作为结直肠癌（CRC）人群筛查的补充或有效替代方法。本研究的目的是比较不同蛋白质组学技术测量的蛋白质的诊断潜力。在 56 例 CRC 患者和 99 例无肿瘤参与者的血浆样本中，使用邻近延伸分析（PEA）、液相色谱/多重反应监测-质谱（LC/MRM-MS）和定量抗体微阵列（QMA）测量蛋白质生物标志物的浓度。在另一种方法中，使用免疫组全长功能蛋白阵列（IpA）在 30 例 CRC 病例和 30 例无肿瘤参与者的血清样本中测量蛋白质。在所有测量中，（a）PEA 和 LC/MRM-MS、（b）PEA 和 QMA、（c）PEA 和 IpA 以及（d）LC/MRM-MS 和 IpA 测量的比较评估中，有 9、6、35 和 14 个蛋白质生物标志物重叠。进行了相关性分析，并计算了曲线下面积（AUC）以评估每个生物标志物的诊断潜力。进行了 DeLong 检验以评估 AUC 之间的差异。对用 PEA 和 LC/MRM-MS 测量的九个生物标志物的评估显示相关系数>+0.6，AUC 相似，DeLong 值表明胰岛素样生长因子结合蛋白 2（IGFBP2）、基质金属蛋白酶 9（MMP9）和血清对氧磷酶内酯酶 3（PON3）等生物标志物的 AUC 无差异。用 PEA 和 QMA 测量的六个蛋白质的比较显示出良好的相关性，只有一个蛋白质（生长分化因子 15（GDF15））的诊断性能相似。用 IpA 和 PEA 测量的 35 个蛋白质和用 IpA 和 LC/MRM-MS 分析的 14 个蛋白质的比较显示，当用 PEA 和 LC/MRM-MS 测量时，一致性较差，但 AUC 较好。不同蛋白质组学技术的比较表明，新型技术（如 PEA 和 LC/MRM-MS）的性能优于评估的基于阵列的技术，可用于 CRC 的血液蛋白质早期检测。
