Pancreatic Cancer (PC) is a lethal disease with the worst prognosis of all the major malignancies. Due to the lack of early symptoms and appropriate methods to detect pancreatic carcinoma at an early stage as well as its aggressive progression, the disease is often quite advanced by the time a definite diagnosis is established. The 5-year relative survival rate for all stages is approximately 6%. Therefore, detection of PC at an early, surgically resectable stage is the key to decrease mortality and to improve survival. The goal of this research project is to explore a fast, simple and sensitive approach for the early diagnosis of PC. Our preliminary results for the lateral-flow nucleic acid biosensors, quantitative immunochromatographic strip biosensors, and the integrated nucleic-acid and protein biosensors provide the proof-of-concept for the contemplated methodology. We hypothesize that simultaneous detection of miRNAs and protein biomarkers with a nanoparticle-powered chemiluminescent lateral-flow biosensor (NCLFB) array will offer a simple and fast tool for early PC diagnosis with improved specificity. The miR-196a (reported to be a potential miRNA biomarker for a PC diagnosis) and CA 19-9 (an approved biomarker for prognosis and following the course of PC) will be used as model targets to optimize the experimental conditions. The approach will initially develop an ultrasensitive NCLFB based on alkaline phosphatase (ALP)/DNA (or ALP/antibody)-functionalized silica nanoparticle (Si-NP) probes for detecting miR-196a (without polymerase chain reaction (PCR) amplification) and CA 19-9 in plasma, respectively; and subsequently develop an integrated chemiluminescent biosensor for simultaneous detection of miR-196a and CA 19-9 in a single platform. Finally, the NCLFB array will be fabricated and used for the detection of a miRNA panel (miR-16, miR-196a, and miR-210) and protein biomarker panel (CA 19-9, ICAM-1, and OPG).The biosensor array will be tested with plasma samples from PC patients and control groups (healthy donors, liver-disease patients, as well as pancreatitis, pancreatic-cyst, and other cancer [breast, colon, and lung] patients), and the results will be validated with qRT-PCR and enzyme-linked immunosorbent assay. The long-term goal of this project is to develop a simple and fast tool for PC early diagnosis. The project provides a translational component to the COBRE center at North Dakota State University. This platform has the potential to be extended for detecting other biomarkers, monitoring the response to therapy, and providing real-time prognostic information for PC patients.
Pancreatic Cancer is the fourth-leading cause of cancer death in the United States. The high mortality for Pancreatic Cancer is largely attributed to the lack of early detection and screening methods, diagnosis at advanced stage of disease, and ineffective medical treatment. We propose to develop a fast, simple and sensitive approach for the early diagnosis of Pancreatic Cancer by simultaneously identifying microRNA (miRNA) and protein biomarker signatures in plasma using nanoparticle-powered chemiluminescent lateral-flow biosensor technology.
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