Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
F1000Res. 2021 Jun 28;10:509. doi: 10.12688/f1000research.53364.1. eCollection 2021.
In this pilot study, we perform a preliminary comparison of two targeted multiplex proteomics technologies for discerning serum protein concentration changes that may correlate to tumor burden in ovarian cancer (OC) patients. : Using the proximity extension assay (PEA) and Quantibody® Kiloplex Array (QKA), we measured >1,000 proteins in the pre-surgical and post-surgical serum from nine OC patients (N=18 samples). We expect that proteins that have decreased significantly in the post-surgical serum concentration may correlate to tumor burden in each patient. Duplicate sera from two healthy individuals were used as controls (N=4 samples). We employed in-house ELISAs to measure five proteins with large serum concentration changes in pre- and post-surgical sera, from four of the original nine patients and the two original controls. Both platforms showed a weak correlation with clinical cancer antigen 125 (CA125) data. The two multiplexed platforms showed a significant correlation with each other for >400 overlapping proteins. PEA uncovered 15 proteins, while QKA revealed 11 proteins, with more than a two-fold post-surgical decrease in at least six of the nine patients. Validation using single enzyme-linked immunosorbent assays (ELISAs) showed at least a two-fold post-surgical decrease in serum concentration of the same patients, as indicated by the two multiplex assays. Both methods identified proteins that had significantly decreased in post-surgical serum concentration, as well as recognizing proteins that had been implicated in OC patients. Our findings from a limited sample size suggest that novel targeted proteomics platforms are promising tools for identifying candidate serological tumor-related proteins. However further studies are essential for the improvement of accuracy and avoidance of false results.
在这项初步研究中，我们对两种靶向多重蛋白质组学技术进行了初步比较，以辨别可能与卵巢癌 (OC) 患者肿瘤负担相关的血清蛋白浓度变化。我们使用邻近延伸分析 (PEA) 和 Quantibody®Kiloplex 阵列 (QKA) 测量了 9 名 OC 患者术前和术后血清中的 >1000 种蛋白质 (N=18 个样本)。我们预计，术后血清浓度显著降低的蛋白质可能与每个患者的肿瘤负担相关。两名健康个体的重复血清用作对照 (N=4 个样本)。我们使用内部 ELISA 测量了来自最初的 9 名患者中的 4 名和最初的 2 名对照患者的术前和术后血清中 5 种具有较大血清浓度变化的蛋白质。两种平台与临床癌症抗原 125 (CA125) 数据均显示出弱相关性。两种多重化平台之间对于 >400 个重叠蛋白质显示出显著相关性。PEA 发现了 15 种蛋白质，而 QKA 则发现了 11 种蛋白质，在至少 9 名患者中的 6 名以上患者中，术后血清浓度下降了两倍以上。使用单一酶联免疫吸附测定 (ELISA) 进行验证显示，与两种多重检测法相同，至少有 9 名患者中的 6 名患者的血清浓度在术后下降了两倍以上。两种方法均识别出了在术后血清浓度中显著下降的蛋白质，并识别出了与 OC 患者相关的蛋白质。我们从有限的样本量中得出的发现表明，新型靶向蛋白质组学平台是识别候选血清肿瘤相关蛋白质的有前途的工具。然而，进一步的研究对于提高准确性和避免假结果是必不可少的。
