@article{178f16978a074145929626d5d103a15b,
title = "Nanotrap-enabled quantification of KRAS-induced peptide hydroxylation in blood for cancer early detection",
abstract = "Circulating peptide is a potential source of biomarkers for cancer detection. However, the existence of large molecular weight proteins in plasma have a disastrous effect on circulating peptides isolating and detecting. Herein, nanotrap fractionation following by mass spectrometry have been applied to quantify the levels of bradykinin (BK) and hydroxylated bradykinin (Hyp-BK) as a relative measure of KRAS-regulated Prolyl-4-hydroxylase alpha-1 (P4HA1) which may serve as early diagnosis marker for pancreatic ductal adenocarcinoma (PDAC). We found that P4HA1 can be upregulated by KRASG12V, which is a PDAC driver mutation, using HPNE/KRAS and HPNE cells. And we revealed that P4HA1 is overexpressed in PDAC tumors, compared to normal and inflamed pancreatic tissues. RNA interference revealed that P4HA1 activity was primarily responsible for Hyp-BK production. Mass spectrometry analysis revealed that plasma Hyp-BK/BK ratio was higher in PDAC than pancreatitis patients and healthy controls, while the area under the receiver operating characteristic (ROC) curve (AUC) is 0.8209 (95%CI, 0.7269–0.9149). The Hyp-BK/BK association with PDAC was reproduced in another cohort, where this ratio was found to increase with advancing tumor stage. These novel findings paved the way for wider applications of Nanotrap coupled mass spectrometry as a powerful tool for revealing biosignatures from plasma.",
keywords = "bradykinin, hydroxylation level, nanotrap, pancreatic ductal adenocarcinoma",
author = "Zaian Deng and Zhen Zhao and Bo Ning and Jeffery Basilio and Karen Mann and Jie Fu and Yajun Gu and Yuanqing Ye and Xifeng Wu and Jia Fan and Paul Chiao and Ye Hu",
note = "Funding Information: 1 College of Health Science and Environmental Engineering, Shenzhen Technology University, Shenzhen 518118, China 2 Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030, USA 3 Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York 10065, USA 4 Center for Molecular Design and Biomimetics, The Biodesign Institute, Arizona State University, Tempe, Arizona 85287, USA 5 Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA 6 Department of Molecular Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida 33612, USA 7 Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA 8 School of Medical Laboratory, Tianjin Medical University, Tianjin 300203, China 9 Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA 10School of Biological and Health Systems Engineering, Virginia G. Piper Biodesign Center for Personalized Diagnostics, The Biodesign Institute, Arizona State University, Tempe, Arizona 85287, USA § Zaian Deng and Zhen Zhao contributed equally to this work. Funding Information: The work was primarily supported by research funding provided by Arizona Biomedical Research Commission (ABRC) young investigator award and ASU-Mayo seed funds. The authors would like to thank Dr. David Hawke in the Proteomics and Metabolomics Facility at the University of Texas M.D. Anderson Cancer Center for his help in operating the mass spectrometer. The authors would also like to thank Dr. Christopher Lyon in the Biodesign Institute at Arizona State University for editorial assistance. Publisher Copyright: {\textcopyright} 2019, Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature.",
year = "2019",
month = jun,
day = "1",
doi = "10.1007/s12274-019-2405-9",
language = "English (US)",
volume = "12",
pages = "1445--1452",
journal = "Nano Research",
issn = "1998-0124",
publisher = "Press of Tsinghua University",
number = "6",
}