TY - JOUR
T1 - MicroRNA-196a and -196b as potential biomarkers for the early detection of familial pancreatic cancer
AU - Slater, Emily P.
AU - Strauch, Konstantin
AU - Rospleszcz, Susanne
AU - Ramaswamy, Annette
AU - Esposito, Irene
AU - Klöppel, Günter
AU - Matthäi, Elvira
AU - Heeger, Kristin
AU - Fendrich, Volker
AU - Langer, Peter
AU - Bartsch, Detlef K.
N1 - Funding Information:
This work was supported by the Deutsche Krebshilfe (109126 to E.P.S., V.F., P.L., and D.K.B.). There exists no financial or other relationship that might lead to a conflict of interest. We thank Helena Honig and Aninja Baier for their excellent technical assistance. We express our appreciation to all patients who participated in the study.
PY - 2014/8
Y1 - 2014/8
N2 - Screening programs are recommended for individuals at risk (IAR) fromfamilies with familial pancreatic cancer (FPC). However, reliable imaging methods or biomarkers for early diagnosis of pancreatic ductal adenocarcinoma (PC) or its precursor lesions are still lacking. The ability of circulating microRNAs (miRNAs) to discriminate multifocal high-grade precursor lesions or PC from normal was examined. The presence of miRNA-21, -155, -196a, -196b and -210 was analyzed in the serumof transgenic KPCmice to test their ability to distinguish mice with different grades of pancreatic intraepithelial neoplasia (mPanIN1-3) or PC from control mice. Serum levels ofmiR-196a and -196b were significantly higher in mice with PanIN2/3 lesions (n = 10) or PC (n = 8) as compared to control mice (n = 10) or mice with PanIN1 lesions (n = 10; P =.01). In humans, miR-196a and -196b were also diagnostic. Patients with PC, sporadic (n = 9) or hereditary (n=10), and IARwithmultifocal PanIN2/3 lesions (n=5) had significantly higher serumlevels than patients with neuroendocrine pancreatic tumors (n = 10) or chronic pancreatitis (n = 10), IAR with PanIN1 or no PanIN lesions (n = 5), and healthy controls (n = 10). The combination of both miR-196a and -196b reached a sensitivity of 1 and specificity of 0.9 (area under the curve = 0.99) to diagnose PC or high-grade PanIN lesions. In addition, preoperative elevated serumlevels ofmiR-196a and -196b in patientswith PC ormultifocal PanIN2/3 lesions dropped to normal after potential curative resection. The combination of miR-196a and -196b may be a promising biomarker test for the screening of IAR for FPC.
AB - Screening programs are recommended for individuals at risk (IAR) fromfamilies with familial pancreatic cancer (FPC). However, reliable imaging methods or biomarkers for early diagnosis of pancreatic ductal adenocarcinoma (PC) or its precursor lesions are still lacking. The ability of circulating microRNAs (miRNAs) to discriminate multifocal high-grade precursor lesions or PC from normal was examined. The presence of miRNA-21, -155, -196a, -196b and -210 was analyzed in the serumof transgenic KPCmice to test their ability to distinguish mice with different grades of pancreatic intraepithelial neoplasia (mPanIN1-3) or PC from control mice. Serum levels ofmiR-196a and -196b were significantly higher in mice with PanIN2/3 lesions (n = 10) or PC (n = 8) as compared to control mice (n = 10) or mice with PanIN1 lesions (n = 10; P =.01). In humans, miR-196a and -196b were also diagnostic. Patients with PC, sporadic (n = 9) or hereditary (n=10), and IARwithmultifocal PanIN2/3 lesions (n=5) had significantly higher serumlevels than patients with neuroendocrine pancreatic tumors (n = 10) or chronic pancreatitis (n = 10), IAR with PanIN1 or no PanIN lesions (n = 5), and healthy controls (n = 10). The combination of both miR-196a and -196b reached a sensitivity of 1 and specificity of 0.9 (area under the curve = 0.99) to diagnose PC or high-grade PanIN lesions. In addition, preoperative elevated serumlevels ofmiR-196a and -196b in patientswith PC ormultifocal PanIN2/3 lesions dropped to normal after potential curative resection. The combination of miR-196a and -196b may be a promising biomarker test for the screening of IAR for FPC.
UR - http://www.scopus.com/inward/record.url?scp=84907332014&partnerID=8YFLogxK
U2 - 10.1016/j.tranon.2014.05.007
DO - 10.1016/j.tranon.2014.05.007
M3 - Article
AN - SCOPUS:84907332014
SN - 1936-5233
VL - 7
SP - 464
EP - 471
JO - Translational Oncology
JF - Translational Oncology
IS - 4
ER -