TY - JOUR
T1 - Plasma miRNA biomarkers in limited volume samples for detection of early-stage pancreatic cancer
AU - Dittmar, Rachel L.
AU - Liu, Suyu
AU - Tai, Mei Chee
AU - Rajapakshe, Kimal
AU - Huang, Ying
AU - Longton, Gary
AU - DeCapite, Christine
AU - Hurd, Mark W.
AU - Paris, Pamela L.
AU - Kirkwood, Kimberly S.
AU - Coarfa, Cristian
AU - Maitra, Anirban
AU - Brand, Randall E.
AU - Killary, Ann M.
AU - Sen, Subrata
N1 - Publisher Copyright:
© 2021 American Association for Cancer Research.
PY - 2021/7
Y1 - 2021/7
N2 - 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 mL 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 ¼ 0.77; 95% confidence interval (CI), 0.66–0.87], miR-130a-3p (AUC ¼ 0.74; 95% CI, 0.63–0.84), and miR-222-3p (AUC ¼ 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.
AB - 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 mL 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 ¼ 0.77; 95% confidence interval (CI), 0.66–0.87], miR-130a-3p (AUC ¼ 0.74; 95% CI, 0.63–0.84), and miR-222-3p (AUC ¼ 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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U2 - 10.1158/1940-6207.CAPR-20-0303
DO - 10.1158/1940-6207.CAPR-20-0303
M3 - Article
C2 - 33893071
AN - SCOPUS:85109163561
SN - 1940-6207
VL - 14
SP - 729
EP - 740
JO - Cancer Prevention Research
JF - Cancer Prevention Research
IS - 7
ER -