Reference - Detail
|Author||Miyamae M, Komatsu S, Ichikawa D, Kawaguchi T, Hirajima S, Okajima W, Ohashi T, Imamura T, Konishi H, Shiozaki A, Morimura R, Ikoma H, Ochiai T, Okamoto K, Taniguchi H, Otsuji E.|
|Title||Plasma microRNA profiles: identification of miR-744 as a novel diagnostic and prognostic biomarker in pancreatic cancer.|
|Journal||Br. J. Cancer|
BACKGROUND:This study aims to explore novel microRNAs in plasma for screening cancer and predicting clinical outcomes in pancreatic cancer (PCa) patients using a microRNA array-based approach.
METHODS:We used the Toray 3D-Gene microRNA array-based approach to compare plasma levels between PCa patients and healthy volunteers.
RESULTS:(1) Six oncogenic microRNAs (miR-615-5p, -744, -575, -557, -675, and -550a) with high expression in plasma were selected. (2) By quantitative RT-PCR using plasma samples from 94 PCa patients and 68 healthy volunteers, a significantly higher level of plasma miR-744 in PCa patients than in healthy volunteers was validated in small-scale analysis (P=0.0038), two independent cohort analyses, and large-scale analysis (P<0.0001, AUC 0.8307). (3) miR-744 expression was significantly higher in PCa tissues (P=0.0069) and PCa cell lines (P=0.0074) than in normal tissues and fibroblasts, respectively. Preoperative plasma level of miR-744 was significantly reduced in postoperative samples (P=0.0063). (4) A high level of plasma miR-744, which was correlated with lymph node metastasis (P=0.0407) and recurrences (P=0.0376), was an independent poor prognostic factor of PCa patients after pancreatectomy (P=0.0007, HR 21.2 (3.17-436)). Furthermore, a high level of plasma miR-744 contributed to poorer progression-free survival of non-operable PCa patients who underwent gemcitabine-based chemotherapy (P=0.0533). Overexpression of miR-744 in PCa cells induced significant chemoresistance to gemcitabine in vitro.
CONCLUSIONS:Plasma miR-744 might be useful biomarker for screening PCa, monitoring, and predicting poor prognosis and chemoresistance in PCa patients.
|MeSH||Aged Biomarkers, Tumor / blood* Biomarkers, Tumor / genetics* Cell Line, Tumor Cell Proliferation / drug effects Deoxycytidine / administration & dosage Deoxycytidine / analogs & derivatives Deoxycytidine / pharmacology Drug Resistance, Neoplasm Female Humans Lymph Nodes / pathology Lymphatic Metastasis Male MicroRNAs / blood* Middle Aged Oligonucleotide Array Sequence Analysis Pancreatic Neoplasms / blood Pancreatic Neoplasms / genetics* Pancreatic Neoplasms / pathology* Pancreatic Neoplasms / surgery Prognosis Sequence Analysis, RNA Up-Regulation|
|Human and Animal Cells||PK-45H(RCB1973) PANC-1(RCB2095) PK-59(RCB1901) KP4-1(RCB1006) PK-1(RCB1972)|