Plasma miRNA Biomarkers in Limited Volume Samples for Detection of Early-stage Pancreatic Cancer.


Journal

Cancer prevention research (Philadelphia, Pa.)
ISSN: 1940-6215
Titre abrégé: Cancer Prev Res (Phila)
Pays: United States
ID NLM: 101479409

Informations de publication

Date de publication:
07 2021
Historique:
received: 11 06 2020
revised: 11 12 2020
accepted: 21 04 2021
pubmed: 25 4 2021
medline: 11 3 2022
entrez: 24 4 2021
Statut: ppublish

Résumé

Early detection of pancreatic ductal adenocarcinoma (PDAC) is key to improving patient outcomes; however, PDAC is usually diagnosed late. Therefore, blood-based minimally invasive biomarker assays for limited volume clinical samples are urgently needed. A novel miRNA profiling platform (Abcam Fireplex-Oncology Panel) was used to investigate the feasibility of developing early detection miRNA biomarkers with 20 μL plasma from a training set (58 stage II PDAC cases and 30 controls) and two validation sets (34 stage II PDAC cases and 25 controls; 44 stage II PDAC cases and 18 controls). miR-34a-5p [AUC = 0.77; 95% confidence interval (CI), 0.66-0.87], miR-130a-3p (AUC = 0.74; 95% CI, 0.63-0.84), and miR-222-3p (AUC = 0.70; 95% CI, 0.58-0.81) were identified as significantly differentially abundant in plasma from stage II PDAC versus controls. Although none of the miRNAs individually outperformed the currently used serologic biomarker for PDAC, carbohydrate antigen 19-9 (CA19-9), combining the miRNAs with CA 19-9 improved AUCs from 0.89 (95% CI, 0.81-0.95) for CA 19-9 alone to 0.92 (95% CI, 0.86-0.97), 0.94 (95% CI, 0.89-0.98), and 0.92 (95% CI, 0.87-0.97), respectively. Gene set enrichment analyses of transcripts correlated with high and low expression of the three miRNAs in The Cancer Genome Atlas PDAC sample set. These miRNA biomarkers, assayed in limited volume plasma together with CA19-9, discriminate stage II PDAC from controls with good sensitivity and specificity. Unbiased profiling of larger cohorts should help develop an informative early detection biomarker assay for diagnostic settings. PREVENTION RELEVANCE: Development of minimally invasive biomarker assays for detection of premalignant disease and early-stage pancreatic cancer is key to improving patient survival. This study describes a limited volume plasma miRNA biomarker assay that can detect early-stage resectable pancreatic cancer in clinical samples necessary for effective prevention and clinical intervention.

Identifiants

pubmed: 33893071
pii: 1940-6207.CAPR-20-0303
doi: 10.1158/1940-6207.CAPR-20-0303
pmc: PMC8818322
mid: NIHMS1699021
doi:

Substances chimiques

CA-19-9 Antigen 0
MicroRNAs 0

Types de publication

Journal Article Observational Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

729-740

Subventions

Organisme : NCI NIH HHS
ID : U01 CA200468
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA200466
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA252965
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA196403
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA217789
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA221707
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA214263
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES030285
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA125123
Pays : United States

Informations de copyright

©2021 American Association for Cancer Research.

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Auteurs

Rachel L Dittmar (RL)

Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas.
University of Texas MD Anderson Cancer Center UT Health Graduate School of Biomedical Sciences, Houston, Texas.

Suyu Liu (S)

University of Texas MD Anderson Cancer Center UT Health Graduate School of Biomedical Sciences, Houston, Texas.
Department of Biostatistics, Division of Science, University of Texas MD Anderson Cancer Center, Houston, Texas.

Mei Chee Tai (MC)

Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas.

Kimal Rajapakshe (K)

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas.

Ying Huang (Y)

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Department of Biostatistics University of Washington, Seattle, Washington.

Gary Longton (G)

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.

Christine DeCapite (C)

Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Mark W Hurd (MW)

Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas.

Pamela L Paris (PL)

Department of Urology and Division of Hematology Oncology, UCSF Helen Diller Cancer Research Center, San Francisco, California.

Kimberly S Kirkwood (KS)

Department of Surgery, Division of General Surgery, UCSF Helen Diller Cancer Research Center, San Francisco, California.

Cristian Coarfa (C)

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas.
Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas.

Anirban Maitra (A)

Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas.
University of Texas MD Anderson Cancer Center UT Health Graduate School of Biomedical Sciences, Houston, Texas.

Randall E Brand (RE)

Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Ann M Killary (AM)

Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas.
University of Texas MD Anderson Cancer Center UT Health Graduate School of Biomedical Sciences, Houston, Texas.

Subrata Sen (S)

Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas. ssen@mdanderson.org.
University of Texas MD Anderson Cancer Center UT Health Graduate School of Biomedical Sciences, Houston, Texas.

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