Park Jiyoung, Choi Yonghwan, Namkung Junghyun, Yi Sung Gon, Kim Hyunsoo, Yu Jiyoung, Kim Yongkang, Kwon Min-Seok, Kwon Wooil, Oh Do-Youn, Kim Sun-Whe, Jeong Seung-Yong, Han Wonshik, Lee Kyu Eun, Heo Jin Seok, Park Joon Oh, Park Joo Kyung, Kim Song Cheol, Kang Chang Moo, Lee Woo Jin, Lee Seungyeoun, Han Sangjo, Park Taesung, Jang Jin-Young, Kim Youngsoo
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul, Korea.
Oncotarget. 2017 Oct 16;8(54):93117-93130. doi: 10.18632/oncotarget.21861. eCollection 2017 Nov 3.
Due to its high mortality rate and asymptomatic nature, early detection rates of pancreatic ductal adenocarcinoma (PDAC) remain poor. We measured 1000 biomarker candidates in 134 clinical plasma samples by multiple reaction monitoring-mass spectrometry (MRM-MS). Differentially abundant proteins were assembled into a multimarker panel from a training set (n=684) and validated in independent set (n=318) from five centers. The level of panel proteins was also confirmed by immunoassays. The panel including leucine-rich alpha-2 glycoprotein (LRG1), transthyretin (TTR), and CA19-9 had a sensitivity of 82.5% and a specificity of 92.1%. The triple-marker panel exceeded the diagnostic performance of CA19-9 by more than 10% (AUC = 0.826, AUC= 0.931, P < 0.01) in all PDAC samples and by more than 30% (AUC = 0.520, AUC = 0.830, P < 0.001) in patients with normal range of CA19-9 (<37U/mL). Further, it differentiated PDAC from benign pancreatic disease (AUC = 0.812, AUC = 0.892, P < 0.01) and other cancers (AUC = 0.796, AUC = 0.899, P < 0.001). Overall, the multimarker panel that we have developed and validated in large-scale samples by MRM-MS and immunoassay has clinical applicability in the early detection of PDAC.
由于胰腺导管腺癌（PDAC）死亡率高且具有无症状性，其早期检测率仍然很低。我们通过多反应监测质谱（MRM-MS）在134份临床血浆样本中检测了1000种生物标志物候选物。将差异丰富的蛋白质从训练集（n = 684）组装成多标志物组合，并在来自五个中心的独立集（n = 318）中进行验证。组合蛋白的水平也通过免疫测定得到确认。包括富含亮氨酸的α-2糖蛋白（LRG1）、甲状腺素转运蛋白（TTR）和CA19-9的组合具有82.5%的灵敏度和92.1%的特异性。在所有PDAC样本中，三标志物组合的诊断性能比CA19-9高出10%以上（AUC = 0.826，AUC = 0.931，P < 0.01），在CA19-9正常范围（<37U/mL）的患者中高出30%以上（AUC = 0.520，AUC = 0.830，P < 0.001）。此外，它还能将PDAC与良性胰腺疾病（AUC = 0.812，AUC = 0.892，P < 0.01）和其他癌症（AUC = 0.796，AUC = 0.899，P < 0.001）区分开来。总体而言，我们通过MRM-MS和免疫测定在大规模样本中开发并验证的多标志物组合在PDAC的早期检测中具有临床适用性。
