An Exosome-based Transcriptomic Signature for Noninvasive, Early Detection of Patients With Pancreatic Ductal Adenocarcinoma: A Multicenter Cohort Study.

Autor:	Nakamura K; Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Monrovia, California., Zhu Z; Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Monrovia, California; Department of Surgery, The Chinese University of Hong Kong. Prince of Wales Hospital, Shatin, N.T., Hong Kong, SAR, China; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, China., Roy S; Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Monrovia, California., Jun E; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Ulsan University College of Medicine and Asan Medical Center, Seoul, Korea., Han H; The Translational Genomics Research Institute, Phoenix, Arizona., Munoz RM; The Translational Genomics Research Institute, Phoenix, Arizona., Nishiwada S; Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Monrovia, California., Sharma G; Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Monrovia, California., Cridebring D; The Translational Genomics Research Institute, Phoenix, Arizona., Zenhausern F; Center for Applied NanoBioscience and Medicine, University of Arizona College of Medicine-Phoenix, Phoenix, Arizona., Kim S; Department of Electrical and Computer Engineering, Roy G. Perry College of Engineering, Prairie View A&M University, Prairie View, Texas., Roe DJ; Department of Epidemiology and Biostatistics, The University of Arizona, Tucson, Arizona., Darabi S; Hoag Family Center Institute, Newport Beach, California., Han IW; Division of Hepato-Biliary Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea., Evans DB; Department of Surgery, The Medical College of Wisconsin, Milwaukee, Wisconsin., Yamada S; Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan., Demeure MJ; The Translational Genomics Research Institute, Phoenix, Arizona; Hoag Family Center Institute, Newport Beach, California., Becerra C; Baylor Scott and White Research Institute, Baylor University Medical Center, Dallas, Texas., Celinski SA; Baylor Scott and White Research Institute, Baylor University Medical Center, Dallas, Texas., Borazanci E; HonorHealth Research Institute, Scottsdale, Arizona., Tsai S; Department of Surgery, The Medical College of Wisconsin, Milwaukee, Wisconsin., Kodera Y; Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan., Park JO; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea., Bolton JS; Department of Surgery, Ochsner Clinic Foundation, New Orleans, Louisiana., Wang X; Department of Surgery, The Chinese University of Hong Kong. Prince of Wales Hospital, Shatin, N.T., Hong Kong, SAR, China. Electronic address: xinwang@cuhk.edu.hk., Kim SC; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Ulsan University College of Medicine and Asan Medical Center, Seoul, Korea. Electronic address: drksc@amc.seoul.kr., Von Hoff D; The Translational Genomics Research Institute, Phoenix, Arizona. Electronic address: dvh@Tgen.org., Goel A; Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Monrovia, California; City of Hope Comprehensive Cancer Center, Duarte, California. Electronic address: ajgoel@coh.org.
Jazyk:	angličtina
Zdroj:	Gastroenterology [Gastroenterology] 2022 Nov; Vol. 163 (5), pp. 1252-1266.e2. Date of Electronic Publication: 2022 Jul 16.
DOI:	10.1053/j.gastro.2022.06.090
Abstrakt:	Background & Aims: Pancreatic ductal adenocarcinoma (PDAC) incidence is rising worldwide, and most patients present with an unresectable disease at initial diagnosis. Measurement of carbohydrate antigen 19-9 (CA19-9) levels lacks adequate sensitivity and specificity for early detection; hence, there is an unmet need to develop alternate molecular diagnostic biomarkers for PDAC. Emerging evidence suggests that tumor-derived exosomal cargo, particularly micro RNAs (miRNAs), offer an attractive platform for the development of cancer-specific biomarkers. Herein, genomewide profiling in blood specimens was performed to develop an exosome-based transcriptomic signature for noninvasive and early detection of PDAC. Methods: Small RNA sequencing was undertaken in a cohort of 44 patients with an early-stage PDAC and 57 nondisease controls. Using machine-learning algorithms, a panel of cell-free (cf) and exosomal (exo) miRNAs were prioritized that discriminated patients with PDAC from control subjects. Subsequently, the performance of the biomarkers was trained and validated in independent cohorts (n = 191) using quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. Results: The sequencing analysis initially identified a panel of 30 overexpressed miRNAs in PDAC. Subsequently using qRT-PCR assays, the panel was reduced to 13 markers (5 cf- and 8 exo-miRNAs), which successfully identified patients with all stages of PDAC (area under the curve [AUC] = 0.98 training cohort; AUC = 0.93 validation cohort); but more importantly, was equally robust for the identification of early-stage PDAC (stages I and II; AUC = 0.93). Furthermore, this transcriptomic signature successfully identified CA19-9 negative cases (<37 U/mL; AUC = 0.96), when analyzed in combination with CA19-9 levels, significantly improved the overall diagnostic accuracy (AUC = 0.99 vs AUC = 0.86 for CA19-9 alone). Conclusions: In this study, an exosome-based liquid biopsy signature for the noninvasive and robust detection of patients with PDAC was developed. (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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