期刊
CANCER PREVENTION RESEARCH
卷 14, 期 7, 页码 729-739出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1940-6207.CAPR-20-0303
关键词
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类别
资金
- University of Texas MD Anderson Cancer Center Pancreatic Cancer Moonshot Program
- Cancer Prevention Research Institute of Texas [RP180392]
- NCI at the NIH [1 U01 CA214263, P50CA221707, U01CA196403, U01CA200468, U01 CA200466]
- John J. Kopchick Fellowship from the University Of Texas MD Anderson UT Health Graduate School of Biomedical Sciences
- National Institutes of Health Translational Genomics and Precision Medicine in Cancer T32 Training Program from the NCI [5T32CA217789-03]
- Cancer Prevention Institute of Texas (CPRIT) [RP170005]
- NIEHS [1P30ES030285, 1P42ES0327725]
- NIH [CA125123]
The study identified miR-34a-5p, miR-130a-3p, and miR-222-3p as significantly differentially abundant in plasma from stage II PDAC cases, and when combined with CA19-9, improved the diagnostic accuracy for PDAC. Further analysis of larger cohorts is needed to develop an effective early detection biomarker assay for clinical settings.
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 mu L 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.
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