Plasma microRNA profiles: identification of miR-744 as a novel diagnostic and prognostic biomarker in pancreatic cancer

Br J Cancer. 2015 Nov 17;113(10):1467-76. doi: 10.1038/bjc.2015.366. Epub 2015 Oct 27.

Abstract

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 terms

  • 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
  • Gemcitabine
  • 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

Substances

  • Biomarkers, Tumor
  • MIRN744 microRNA, human
  • MicroRNAs
  • Deoxycytidine
  • Gemcitabine