4.5 Article

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

Journal

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 23, Issue 2, Pages 1396-1405

Publisher

WILEY
DOI: 10.1111/jcmm.14042

Keywords

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

Funding

  1. Natural Science Foundation of Shandong Province [ZR2017ZB0419]
  2. Taishan Scholar Program of Shandong Province
  3. Fundamental Research Funds of Shandong University [2017BTS01, 2017JC031, 2018JC002]
  4. Science and Technology Development Plan Project of Jinan [201602154]
  5. National Natural Science Foundation of China [81472025, 81501822, 81772271, 81873977]
  6. Shandong Technological Development Project [2016CYJS01A02]

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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.

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