A Plasma-Derived Protein-Metabolite Multiplexed Panel for Early-Stage Pancreatic Cancer
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
Authors: Fahrmann, Johannes F.; Bantis, Leonidas E.; Capello, Michela; Scelo, Ghislaine; Dennison, Jennifer B.; Patel, Nikul; Murage, Eunice; Vykoukal, Jody; Kundnani, Deepali L.; Foretova, Lenka; Fabianova, Eleonora; Holcatova, Ivana; Janout, Vladimir; Feng, Ziding; Yip-Schneider, Michele; Zhang, Jianjun; Brand, Randall; Taguchi, Ayumu; Maitra, Anirban; Brennan, Paul; Schmidt, C. Max; Hanash, Samir
Abstract
Background: We applied a training and testing approach to develop and validate a plasma metabolite panel for the detection of early-stage pancreatic ductal adenocarcinoma (PDAC) alone and in combination with a previously validated protein panel for early-stage PDAC. Methods: A comprehensive metabolomics platform was initially applied to plasmas collected from 20 PDAC cases and 80 controls. Candidate markers were filtered based on a second independent cohort that included nine invasive intraductal papillary mucinous neoplasm cases and 51 benign pancreatic cysts. Blinded validation of the resulting metabolite panel was performed in an independent test cohort consisting of 39 resectable PDAC cases and 82 matched healthy controls. The additive value of combining the metabolite panel with a previously validated protein panel was evaluated. Results: Five metabolites (acetylspermidine, diacetylspermine, an indole-derivative, and two lysophosphatidylcholines) were selected as a panel based on filtering criteria. A combination rule was developed for distinguishing between PDAC and healthy controls using the Training Set. In the blinded validation study with early-stage PDAC samples and controls, the five metabolites yielded areas under the curve (AUCs) ranging from 0.726 to 0.842, and the combined metabolite model yielded an AUC of 0.892 (95% confidence interval [CI] = 0.828 to 0.956). Performance was further statistically significantly improved by combining the metabolite panel with a previously validated protein marker panel consisting of CA 19-9, LRG1, and TIMP1 (AUC = 0.924, 95% CI = 0.864 to 0.983, comparison DeLong test one-sided P = .02). Conclusions: A metabolite panel in combination with CA19-9, TIMP1, and LRG1 exhibited substantially improved performance in the detection of early-stage PDAC compared with a protein panel alone.
Urinary Proteomics Identifying Novel Biomarkers for the Diagnosis of Adult-Onset Still's Disease
FRONTIERS IN IMMUNOLOGY
Authors: Sun, Yue; Wang, Fan; Zhou, Zhuochao; Teng, Jialin; Su, Yutong; Chi, Huihui; Wang, Zhihong; Hu, Qiongyi; Jia, Jinchao; Liu, Tingting; Liu, Honglei; Cheng, Xiaobing; Shi, Hui; Tan, Yun; Yang, Chengde; Ye, Junna
Abstract
Adult-onset Still's disease (AOSD) is a systemic, multigenic autoinflammatory disease, and the diagnosis of AOSD must rule out neoplasms, infections, and other autoimmune diseases. Development of a rapid and efficient but non-invasive diagnosis method is urgently needed for improving AOSD therapy. In this study, we first performed a urinary proteomic study using isobaric tags for relative and absolute quantification (iTRAQ) labeling combined with liquid chromatography-tandem mass spectrometry analysis in patients with AOSD and healthy control (HC) subjects. The urinary proteins were enriched in pathways of the innate immune system and neutrophil degranulation, and we identified that the alpha-1-acid glycoprotein 1 (LRG1), orosomucoid 1 (ORM1), and ORM2 proteins were highly expressed in patients with AOSD. The elevated urine levels of LRG1, ORM1, and ORM2 were further validated by enzyme-linked immunosorbent assay in active patients with AOSD, disease controls, and HC subjects. Receiver operating characteristic curves showed that the areas under the curve of LRG1, ORM1, and ORM2 were 0.700, 0.837, and 0.736, respectively (allp< 0.05). Furthermore, we found that the urine levels of LRG1, ORM1, and ORM2 were positively correlated with the systemic score and erythrocyte sedimentation rate and that the urine levels of LRG1 were positively correlated with interleukin 1 beta (IL-1 beta), IL-6, and IL-18 levels, whereas the urine levels of ORM1 were positively correlated with the IL-1 beta level. Together, our study identified novel urinary markers for non-invasive and simple screening of AOSD.