The Use of Three Long Non-Coding RNAs as Potential Prognostic Indicators of Astrocytoma

PLoS One. 2015 Aug 7;10(8):e0135242. doi: 10.1371/journal.pone.0135242. eCollection 2015.

Abstract

Long noncoding RNAs (lncRNAs) are pervasively transcribed and play a key role in tumorigenesis. The aim of the study was to determine the lncRNA expression profile in astrocytomas and to assess its potential clinical value. We performed a three-step analysis to establish the lncRNA profile for astrocytoma: a) the lncRNA expression was examined on 3 astrocytomas as well as 3 NATs (normal adjacent tissues) using the lncRNA microarray; b) the top-hits were validated in 40 astrocytomas (WHO grade II-IV) by quantitative real time-PCR (qRT-PCR); c) the hits with significant differences were re-evaluated using qRT-PCR in 90 astrocytomas. Finally, 7 lncRNAs were found to have a significantly different expression profile in astrocytoma samples compared to the NAT samples. Unsupervised clustering analysis further revealed the potential of the 7-lncRNA profile to differentiate between tumors and NAT samples. The upregulation of ENST00000545440 and NR_002809 was associated with advanced clinical stages of astrocytoma. Using Kaplan-Meier survival analysis, we showed that the low expression of BC002811 or XLOC_010967, or the high expression of NR_002809 was significantly associated with poor patient survival. Moreover, Cox proportional hazard regression analysis revealed that this prognostic impact was independent of other clinicopathological factors. Our results indicate that the lncRNA profile may be a potential prognostic biomarker for the prediction of post-surgical outcomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aquaporin 1 / metabolism
  • Astrocytoma / diagnosis*
  • Astrocytoma / genetics
  • Astrocytoma / metabolism*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Brain / metabolism*
  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Case-Control Studies
  • Cluster Analysis
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • Protein Phosphatase 2 / metabolism
  • RNA, Long Noncoding / genetics*
  • ROC Curve
  • Real-Time Polymerase Chain Reaction
  • Tenascin / metabolism
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • Extracellular Matrix Proteins
  • HAPLN4 protein, human
  • Nerve Tissue Proteins
  • PPP2R2C protein, human
  • RNA, Long Noncoding
  • Tenascin
  • Aquaporin 1
  • Protein Phosphatase 2

Associated data

  • GEO/GSE58276

Grants and funding

This work was supported by National Natural Science Foundation of China: 31071046 (YLY), 81302197 (FZ); Changzhou Social Development Project: CS20102010 (SNW); Changzhou Health Bureau Project: ZD201007 (SNW); Changzhou Science Technology Bureau Guiding Project: CY20119004 (FZ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.