Dataset Information

Development of a panel of DNA Aptamers with High Affinity for Pancreatic Ductal Adenocarcinoma.

ABSTRACT: Pancreatic cancer costs nearly 40,000 lives in the U.S. each year and has one of the lowest survival rates among cancers. Effective treatment of pancreatic ductal adenocarcinoma is hindered by lack of a reliable biomarker. To address this challenge, aptamers were selected by cell-SELEX (Systematic Evolution of Ligands by EXponential enrichment) targeting human pancreatic ductal adenocarcinoma (PL45). Five promising aptamers presenting low Kd values and good specificity were generated. Among these five aptamers, one was tailored into a nanostructure carrying a high drug payload for specific drug delivery. The results show a viability of almost 80% for negative cells while only 50% of the target cells remained alive after 48 h incubation. These results lead to the conclusion that further research could reveal protein biomarkers specific to pancreatic adenocarcinoma, with probes available for early detection.

SUBMITTER: Champanhac C

PROVIDER: S-EPMC4658478 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Development of a panel of DNA Aptamers with High Affinity for Pancreatic Ductal Adenocarcinoma.

Champanhac Carole C Teng I-Ting IT Cansiz Sena S Zhang Liqin L Wu Xiaoqiu X Zhoa Zilong Z Fu Ting T Tan Weihong W

Scientific reports 20151125

Pancreatic cancer costs nearly 40,000 lives in the U.S. each year and has one of the lowest survival rates among cancers. Effective treatment of pancreatic ductal adenocarcinoma is hindered by lack of a reliable biomarker. To address this challenge, aptamers were selected by cell-SELEX (Systematic Evolution of Ligands by EXponential enrichment) targeting human pancreatic ductal adenocarcinoma (PL45). Five promising aptamers presenting low Kd values and good specificity were generated. Among thes ...[more]

PMID: 26603187

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Project description:Pancreatic ductal adenocarcinoma (PDAC) suffers from lack of an effective diagnostic method, limiting improvement in patient survival. Although the FDA-approved biomarker CA19-9 has been used for detection and surveillance of PDAC, its clinical utility is generally regarded to be limited due to its suboptimal diagnostic performance. Liquid chromatography-mass spectrometry (LC-MS) has emerged as a burgeoning technology in clinical proteomics, and identified a plethora of protein biomarker candidates for PDAC. Yet few if any has successfully transitioned into clinical practice. This translational standstill is owed partly to the limited considerations of practical needs and perspectives of clinical implementation in the course of a biomarker pipeline, such as demonstrating analytical validity of proposed biomarkers, which is critical to turning research-grade assays to clinical-grade tests. Here, we developed a fit-for-purpose multi-marker panel for PDAC diagnosis by consolidating analytically robust biomarkers as well as employing a relatively simple LC-MS method. In the discovery phase, we systematically collected putative biomarkers from both in-house proteomics data and the large volume of literature documenting PDAC biomarkers. In the verification phase, we developed a multiple-reaction monitoring (MRM)-MS-based proteomic assay using surrogate peptides that passed stringent analytical validation criteria. Given the intended use of our panel (i.e., primary screening), we adopted a high-throughput protocol including short gradient (<10 min) and simple sample preparation (no depletion or enrichment steps). To further facilitate clinical implementation, we performed verification of our panel on serum samples, which are usually the preferred biospecimen available in clinical settings. We developed a stacking ensemble model based on our final panel of 12 protein biomarkers combined with CA19-9, which showed improved diagnostic performance compared to using CA19-9 alone (AUC 0.919 and 0.830, respectively). A large-scale clinical validation study is underway to demonstrate the clinical validity of our panel.

Dataset Information

Development of a panel of DNA Aptamers with High Affinity for Pancreatic Ductal Adenocarcinoma.

Publications

Development of a panel of DNA Aptamers with High Affinity for Pancreatic Ductal Adenocarcinoma.

Similar Datasets

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