Kim Hongbeom, Kang Kyung Nam, Shin Yong Sung, Byun Yoonhyeong, Han Youngmin, Kwon Wooil, Kim Chul Woo, Jang Jin-Young
Departments of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
BIOINFRA Life Science Inc., Seoul 03127, Korea.
Cancers (Basel). 2020 Jun 1;12(6):1443. doi: 10.3390/cancers12061443.
A single tumor marker has a low diagnostic value in pancreatic cancer. Combinations of multiple biomarkers and unique analysis algorithms can be applied to overcome these limitations. This study sought to develop diagnostic algorithms using multiple biomarker panels and to validate their performance in the diagnosis of pancreatic ductal adenocarcinoma (PDAC). We used blood samples from 180 PDAC patients and 573 healthy controls. Candidate markers consisted of 11 markers that are commonly expressed in various cancers and which have previously demonstrated increased expression in pancreatic cancer. Samples were divided into training and validation sets. Five linear or non-linear classification methods were used to determine the optimal model. Differences were identified in 10 out of the 11 markers tested. We identified 2047 combinations, all of which were applied to 5 separate algorithms. The new biomarker combination consisted of 6 markers (ApoA1, CA125, CA19-9, CEA, ApoA2, and TTR). The area under the curve, specificity, and sensitivity were 0.992, 95%, and 96%, respectively, in the training set. Meanwhile, the measures were 0.993, 96%, and 93% in the validation set. This study demonstrated the utility of multiple biomarker combinations in the early detection of PDAC. A diagnostic panel of 6 biomarkers was developed and validated. These algorithms will assist in the early diagnosis of PDAC.
单一肿瘤标志物在胰腺癌诊断中的价值较低。可应用多种生物标志物组合及独特分析算法来克服这些局限性。本研究旨在开发使用多种生物标志物组合的诊断算法,并验证其在胰腺导管腺癌(PDAC)诊断中的性能。我们使用了180例PDAC患者和573例健康对照者的血样。候选标志物包括11种在多种癌症中普遍表达且先前已证实在胰腺癌中表达增加的标志物。样本被分为训练集和验证集。使用五种线性或非线性分类方法来确定最佳模型。在所测试的11种标志物中有10种存在差异。我们确定了2047种组合,并将所有组合应用于5种不同算法。新的生物标志物组合由6种标志物组成(载脂蛋白A1、癌抗原125、癌抗原19-9、癌胚抗原、载脂蛋白A2和甲状腺素运载蛋白)。在训练集中,曲线下面积、特异性和敏感性分别为0.992、95%和96%。同时,在验证集中,这些指标分别为0.993、96%和93%。本研究证明了多种生物标志物组合在PDAC早期检测中的效用。开发并验证了一个由6种生物标志物组成的诊断面板。这些算法将有助于PDAC的早期诊断。