Evaluation of serum exosomal LncRNA-based biomarker panel for diagnosis and recurrence prediction of bladder cancer

J Cell Mol Med. 2019 Feb;23(2):1396-1405. doi: 10.1111/jcmm.14042. Epub 2018 Nov 23.

Abstract

Exosomes are small membrane vesicles released by many cells. These vesicles can mediate cellular communications by transmitting active molecules including long non-coding RNAs (lncRNAs). In this study, our aim was to identify a panel of lncRNAs in serum exosomes for the diagnosis and recurrence prediction of bladder cancer (BC). The expressions of 11 candidate lncRNAs in exosome were investigated in training set (n = 200) and an independent validation set (n = 320) via quantitative real-time PCR. A three-lncRNA panel (PCAT-1, UBC1 and SNHG16) was finally identified by multivariate logistic regression model to provide high diagnostic accuracy for BC with an area under the receiver-operating characteristic curve (AUC) of 0.857 and 0.826 in training set and validation set, respectively, which was significantly higher than that of urine cytology. The corresponding AUCs of this panel for patients with Ta, T1 and T2-T4 were 0.760, 0.827 and 0.878, respectively. In addition, Kaplan-Meier analysis showed that non-muscle-invasive BC (NMIBC) patients with high UBC1 expression had significantly lower recurrence-free survival (P = 0.01). Multivariate Cox analysis demonstrated that UBC1 was independently associated with tumour recurrence of NMIBC (P = 0.018). Our study suggested that lncRNAs in serum exosomes may serve as considerable diagnostic and prognostic biomarkers of BC.

Keywords: biomarkers; bladder cancer; diagnosis; long non-coding RNA; recurrence; serum exosomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Case-Control Studies
  • Exosomes / genetics*
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / blood
  • Neoplasm Recurrence, Local / diagnosis*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / surgery
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • ROC Curve
  • Urinary Bladder Neoplasms / blood
  • Urinary Bladder Neoplasms / diagnosis*
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / surgery

Substances

  • Biomarkers, Tumor
  • RNA, Long Noncoding
  • SNHG16 lncRNA, human
  • long non-coding RNA PCAT1, human