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

组织 MicroRNA 谱作为可切除胰腺导管腺癌和壶腹部癌患者的诊断和预后生物标志物

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作者:Dan Calatayud, Christian Dehlendorff, Mogens K Boisen, Jane Preuss Hasselby, Nicolai Aagaard Schultz, Jens Werner, Heike Immervoll, Anders Molven, Carsten Palnæs Hansen, Julia S Johansen

Background

The

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.

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, -222-5p, 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).

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