Tissue MicroRNA profiles as diagnostic and prognostic biomarkers in patients with resectable pancreatic ductal adenocarcinoma and periampullary cancers

被引:55
|
作者
Calatayud, Dan [1 ,11 ]
Dehlendorff, Christian [2 ]
Boisen, Mogens K. [3 ]
Hasselby, Jane Preuss [4 ]
Schultz, Nicolai Aagaard [1 ]
Werner, Jens [5 ]
Immervoll, Heike [6 ,7 ]
Molven, Anders [6 ,8 ]
Hansen, Carsten Palnaes [1 ]
Johansen, Julia S. [3 ,9 ,10 ]
机构
[1] Copenhagen Univ Hosp, Rigshosp, Dept Surg Gastroenterol & Transplantat, Copenhagen, Denmark
[2] Danish Canc Soc, Danish Canc Soc Res Ctr, Copenhagen, Denmark
[3] Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Oncol, Herlev, Denmark
[4] Copenhagen Univ Hosp, Dept Pathol, Rigshospitalet, Copenhagen, Denmark
[5] Univ Munich, LMU, Dept Gen Visceral & Transplant Surg, Munich, Germany
[6] Univ Bergen, Dept Clin Med, Gade Lab Pathol, Bergen, Norway
[7] Alesund Hosp, Dept Pathol, Alesund, Norway
[8] Haukeland Hosp, Dept Pathol, Bergen, Norway
[9] Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Med, Herlev, Denmark
[10] Univ Copenhagen, Fac Hlth & Med Sci, Inst Clin Med, Copenhagen, Denmark
[11] Herlev Univ Hosp, Dept Oncol, Herlev Ringvej 75, DK-2730 Herlev, Denmark
关键词
Ampullary cancer; Biomarkers; microRNA; Pancreatic ductal adenocarcinoma; Pancreatic cancer; EPITHELIAL-MESENCHYMAL TRANSITION; INHIBITS CELL-PROLIFERATION; HUMAN COLORECTAL-CANCER; TUMOR-SUPPRESSOR; LUNG-CANCER; EXPRESSION PATTERNS; MOLECULAR PROFILES; DOWN-REGULATION; BREAST-CANCER; SIGNATURE;
D O I
10.1186/s40364-017-0087-6
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: The aim of this study was to validate previously described diagnostic and prognostic microRNA expression profiles in tissue samples from patients with pancreatic cancer and other periampullary cancers. Methods: Expression of 46 selected microRNAs was studied in formalin-fixed paraffin-embedded tissue from patients with resected pancreatic ductal adenocarcinoma (n = 165), ampullary cancer (n= 59), duodenal cancer (n = 6), distal common bile duct cancer (n = 21), and gastric cancer (n = 20); chronic pancreatitis (n = 39); and normal pancreas (n = 35). The microRNAs were analyzed by PCR using the Fluidigm platform. Results: Twenty-two microRNAs were significantly differently expressed in patients with pancreatic cancer when compared to healthy controls and chronic pancreatitis patients; 17 miRNAs were upregulated (miR-21-5p, -23a-3p, -31-5p, -34c-5p, -93-3p, -135b-3p, -155-5p, -186-5p, -196b-5p, -203, -205-5p, -210, -222-3p, -451, -492, -614, and miR-622) and 5 were downregulated (miR-122-5p, -130b-3p, -216b, -217, and miR-375). MicroRNAs were grouped into diagnostic indices of varying complexity. Ten microRNAs associated with prognosis were identified (let-7 g, miR-29a-5p, -34a-5p, -125a-3p, -146a-5p, -187, -205-5p, -212-3p, -2225-p, and miR-450b-5p). Prognostic indices based on differences in expression of 2 different microRNAs were constructed for pancreatic and ampullary cancer combined and separately (30, 5, and 21 indices). Conclusion: The study confirms that pancreatic cancer tissue has a microRNA expression profile that is different from that of other periampullary cancers, chronic pancreatitis, and normal pancreas. We identified prognostic microRNAs and microRNA indices that were associated with shorter overall survival in patients with radically resected pancreatic cancer.
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页数:18
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