Serum microRNA expression signatures as novel noninvasive biomarkers for prediction and prognosis of muscle-invasive bladder cancer

Oncotarget. 2016 Jun 14;7(24):36733-36742. doi: 10.18632/oncotarget.9166.

Abstract

Noninvasive biomarkers for predicting the risk of muscle-invasive bladder cancer (MIBC) may expedite appropriate therapy and reduce morbidity and cost. Genome-wide miRNA analysis by Miseq sequencing followed by two phases of reverse transcription quantitative real-time PCR (RT-qPCR) assays were performed on serum from 207 MIBC patients, 285 nonmuscle-invasive bladder cancer (NMIBC) patients and 193 controls. A four-miRNA panel (miR-422a-3p, miR-486-3p, miR-103a-3p and miR-27a-3p) was developed for MIBC prediction with an area under the receiver operating characteristic curve (AUC) of 0.894 (95% CI, 0.846-0.931) for training set. Prospective evaluation of the miRNA panel revealed an AUC of 0.880 (95% CI, 0.834 to 0.917) in validation set, which was significantly higher than those of grade and urine cytology (both p < 0.05). Moreover, Kaplan-Meier analysis showed that MIBC patients with low miR-486-3p and miR-103a-3p levels had worse overall survival (p = 0.002 and p = 0.034, respectively). Cox analysis indicated miR-486-3p and miR-103a-3p were independently associated with overall survival of MIBC (p = 0.042 and p = 0.021, respectively). In conclusion, serum miRNA signatures might have considerable clinical values in predicting and providing prognostic information for MIBC.

Keywords: microRNA; muscle-invasive bladder cancer; prediction; prognosis; serum.

MeSH terms

  • Aged
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Female
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • Middle Aged
  • Muscles / pathology
  • Neoplasm Invasiveness
  • Prognosis
  • Prospective Studies
  • Urinary Bladder Neoplasms / blood
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • MIRN103 microRNA, human
  • MIRN486 microRNA, human
  • MicroRNAs