Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Prognostic and clinicopathological significance of long non-coding RNA in glioma


Growing evidence from recent studies have revealed that long non-coding RNA (lncRNA) might be a useful prognostic biomarker for glioma; we therefore conducted the current meta-analysis to evaluate prognostic and clinicopathological predictive value of lncRNA expression for glioma patients. Eligible studies were identified through multiple research strategies in PubMed, EMBASE, Web of Science, and Cochrane Library up to May 2017. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were utilized to calculate patient’s survival. Fourteen eligible studies with 1415 patients were ultimately included in this meta-analysis. Our meta-analysis showed a significant association between high lncRNA expression level and OS in glioma patients (HR 2.09, 95% CI 1.68–2.58, P < 0.001). Subgroup analysis was conducted to explore the potential heterogeneity. As for clinicopathological parameters, lncRNA expression was significantly associated with tumor diameter (< 3 vs ≥ 3 cm, OR 0.39, 95% CI 0.27–0.56, P < 0.001; < 5 vs ≥ 5 cm, OR 0.56, 95% CI 0.34–0.92, P = 0.02), tumor grade (OR 0.21, 95% CI 0.13–0.34, P < 0.001), and Karnofsky Performance Status Scale (OR 2.52, 95% CI 1.54–4.11, P < 0.001). LncRNA may serve as a biomarker for prognosis and clinicopathological features in glioma patients.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4


  1. 1.

    Jiang C, Li X, Zhao H, Liu H (2016) Long non-coding RNAs: potential new biomarkers for predicting tumor invasion and metastasis. Mol Cancer 15:62. https://doi.org/10.1186/s12943-016-0545-z

  2. 2.

    Reon BJ, Anaya J, Zhang Y, Mandell J (2016) Expression of lncRNAs in low-grade gliomas and glioblastoma multiforme: an in silico analysis. 13:e1002192. https://doi.org/10.1371/journal.pmed.1002192

  3. 3.

    Li CH, Chen Y (2013) Targeting long non-coding RNAs in cancers: progress and prospects. Int J Biochem Cell Biol 45:1895–1910. https://doi.org/10.1016/j.biocel.2013.05.030

  4. 4.

    Pan Y, Li C, Chen J, Zhang K, Chu X, Wang R, Chen L (2016) The emerging roles of long noncoding RNA ROR (lincRNA-ROR) and its possible mechanisms in human cancers. Cell Physiol Biochem 40:219–229. https://doi.org/10.1159/000452539

  5. 5.

    Qin X, Yao J, Geng P, Fu X, Xue J, Zhang Z (2014) LncRNA TSLC1-AS1 is a novel tumor suppressor in glioma. Int J Clin Exp Pathol 7:3065–3072

  6. 6.

    Liu S, Mitra R, Zhao MM, Fan W, Eischen CM, Yin F, Zhao Z (2016) The potential roles of long noncoding RNAs (lncRNA) in glioblastoma development. Mol Cancer Ther 15:2977–2986. https://doi.org/10.1158/1535-7163.MCT-16-0320

  7. 7.

    Shi Y, Wang Y, Luan W, Wang P, Tao T, Zhang J, Qian J, Liu N, You Y (2014) Long non-coding RNA H19 promotes glioma cell invasion by deriving miR-675. PLoS One 9:e86295. https://doi.org/10.1371/journal.pone.0086295

  8. 8.

    Yu X, Li Z (2015) Long non-coding RNA HOTAIR: a novel oncogene (review). Mol Med Rep 12:5611–5618. https://doi.org/10.3892/mmr.2015.4161

  9. 9.

    Guo H, Hu G, Yang Q, Zhang P, Kuang W, Zhu X, Wu L (2016) Knockdown of long non-coding RNA CCAT2 suppressed proliferation and migration of glioma cells. Oncotarget 7:81806–81814. https://doi.org/10.18632/oncotarget.13242

  10. 10.

    Bian EB, Li J, Xie YS, Zong G, Li J, Zhao B (2015) LncRNAs: new players in gliomas, with special emphasis on the interaction of lncRNAs with EZH2. J Cell Physiol 230:496–503. https://doi.org/10.1002/jcp.24549

  11. 11.

    Han L, Zhang K, Shi Z, Zhang J, Zhu J, Zhu S, Zhang A, Jia Z, Wang G, Yu S, Pu P, Dong L, Kang C (2012) LncRNA profile of glioblastoma reveals the potential role of lncRNAs in contributing to glioblastoma pathogenesis. Int J Oncol 40:2004–2012. https://doi.org/10.3892/ijo.2012.1413

  12. 12.

    Meseure D, Alsibai KD, Nicolas A, Bieche I, Morillon A (2015) Long noncoding RNAs as new architects in cancer epigenetics, prognostic biomarkers, and potential therapeutic targets. Biomed Res Int 2015:1–14. https://doi.org/10.1155/2015/320214

  13. 13.

    Sun Y, Wang Z, Zhou D (2013) Long non-coding RNAs as potential biomarkers and therapeutic targets for gliomas. Med Hypotheses 81:319–321. https://doi.org/10.1016/j.mehy.2013.04.010

  14. 14.

    Wang L, Yu Z, Sun S, Peng J, Xiao R, Chen S, Zuo X, Cheng Q, Xia Y (2017) Long non-coding RNAs: potential molecular biomarkers for gliomas diagnosis and prognosis. Rev Neurosci 28:375–380. https://doi.org/10.1515/revneuro-2016-0066

  15. 15.

    Parmar MK, Torri V, Stewart L (1998) Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med 17:2815–2834

  16. 16.

    Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR (2007) Practical methods for incorporating summary time-to-event data into meta-analysis. Trials 8:16. https://doi.org/10.1186/1745-6215-8-16

  17. 17.

    Lau J, Ioannidis JP, Schmid CH (1997) Quantitative synthesis in systematic reviews. Ann Intern Med 127:820–826

  18. 18.

    Zhao W, Sun C, Cui Z (2017) A long noncoding RNA UCA1 promotes proliferation and predicts poor prognosis in glioma. Clin Transl Oncol. https://doi.org/10.1007/s12094-016-1597-7

  19. 19.

    Lv QL, Hu L, Chen SH, Sun B, Fu ML, Qin CZ, Qu Q, Wang GH, He CJ, Zhou HH (2016) A long noncoding RNA ZEB1-AS1 promotes tumorigenesis and predicts poor prognosis in glioma. Int J Mol Sci 17. https://doi.org/10.3390/ijms17091431

  20. 20.

    Wang Q, Zhang J, Liu Y, Zhang W, Zhou J, Duan R, Pu P, Kang C, Han L (2016) A novel cell cycle-associated lncRNA, HOXA11-AS, is transcribed from the 5-prime end of the HOXA transcript and is a biomarker of progression in glioma. Cancer Lett 373:251–259. https://doi.org/10.1016/j.canlet.2016.01.039

  21. 21.

    He C, Jiang B, Ma J, Li Q (2016) Aberrant NEAT1 expression is associated with clinical outcome in high grade glioma patients. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 124:169–174. https://doi.org/10.1111/apm.12480

  22. 22.

    Liu C, Sun Y, She X, Tu C, Cheng X, Wang L, Yu Z, Li P, Liu Q, Yang H, Li G, Wu M (2017) CASC2c as an unfavorable prognosis factor interacts with miR-101 to mediate astrocytoma tumorigenesis. Cell Death Dis 8:e2639. https://doi.org/10.1038/cddis.2017.11

  23. 23.

    Chen ZH, Hu HK, Zhang CR, Lu CY, Bao Y, Cai Z, Zou YX, Hu GH, Jiang L (2016) Down-regulation of long non-coding RNA FOXD3 antisense RNA 1 (FOXD3-AS1) inhibits cell proliferation, migration, and invasion in malignant glioma cells. Am J Transl Res 8:4106–4119

  24. 24.

    Jing SY, Lu YY, Yang JK, Deng WY, Zhou Q, Jiao BH (2016) Expression of long non-coding RNA CRNDE in glioma and its correlation with tumor progression and patient survival. Eur Rev Medical Pharmacol Sci 20:3992–3996

  25. 25.

    Yan H, Tian R, Zhang M, Wu J, Ding M, He J (2017) High expression of long noncoding RNA HULC is a poor predictor of prognosis and regulates cell proliferation in glioma. OncoTargets Therapy 10:113–120. https://doi.org/10.2147/ott.s124614

  26. 26.

    Zhang JX, Han L, Bao ZS, Wang YY, Chen LY, Yan W, Yu SZ, Pu PY, Liu N, You YP, Jiang T, Kang CS (2013) HOTAIR, a cell cycle-associated long noncoding RNA and a strong predictor of survival, is preferentially expressed in classical and mesenchymal glioma. Neuro-Oncology 15:1595–1603. https://doi.org/10.1093/neuonc/not131

  27. 27.

    Zhang T, Wang YR, Zeng F, Cao HY, Zhou HD, Wang YJ (2016) LncRNA H19 is overexpressed in glioma tissue, is negatively associated with patient survival, and promotes tumor growth through its derivative miR-675. Eur Rev Medical Pharmacol Sci 20:4891–4897

  28. 28.

    Ma KX, Wang HJ, Li XR, Li T, Su G, Yang P, Wu JW (2015) Long noncoding RNA MALAT1 associates with the malignant status and poor prognosis in glioma. Tumour Biol 36:3355–3359. https://doi.org/10.1007/s13277-014-2969-7

  29. 29.

    Zhuang JJ, Yue M, Zheng YH, Li JP, Dong XY (2016) Long non-coding RNA MVIH acts as a prognostic marker in glioma and its role in cell migration and invasion. Eur Rev Medical Pharmacol Sci 20:4898–4904

  30. 30.

    Zhou Y, Wang DL, Pang Q (2016) Long noncoding RNA SPRY4-IT1 is a prognostic factor for poor overall survival and has an oncogenic role in glioma. Eur Rev Med Pharmacol Sci 20:3035–3039. https://doi.org/10.1016/j.canlet.2016.08.009

  31. 31.

    Hu L, Lv QL, Chen SH, Sun B, Qu Q, Cheng L, Guo Y, Zhou HH, Fan L (2016) Up-regulation of long non-coding RNA AB073614 predicts a poor prognosis in patients with glioma. Int J Environ Res Public Health 13:433. https://doi.org/10.1186/s13041-016-0226-2 10.3390/ijerph13040433

  32. 32.

    Ramos AD, Attenello FJ, Lim DA (2016) Uncovering the roles of long noncoding RNAs in neural development and glioma progression. Neurosci Lett 625:70–79. https://doi.org/10.1016/j.neulet.2015.12.025

  33. 33.

    Zhang XQ, Leung GK (2014) Long non-coding RNAs in glioma: functional roles and clinical perspectives. Neurochem Int 77:78–85. https://doi.org/10.1016/j.neuint.2014.05.008

  34. 34.

    Qureshi IA, Mehler MF (2013) Long non-coding RNAs: novel targets for nervous system disease diagnosis and therapy. Neurotherapeutics 10:632–646. https://doi.org/10.1007/s13311-013-0199-0

  35. 35.

    Kiang KM, Zhang XQ, Leung GK (2015) Long non-coding RNAs: the key players in glioma pathogenesis. Cancers (Basel) 7:1406–1424. https://doi.org/10.3390/cancers7030843

  36. 36.

    Hu GW, Wu L, Kuang W, Chen Y, Zhu XG, Guo H, Lang HL (2017) Knockdown of linc-OIP5 inhibits proliferation and migration of glioma cells through down-regulation of YAP-NOTCH signaling pathway. Gene 610:24–31. https://doi.org/10.1016/j.gene.2017.02.006

  37. 37.

    Li J, Wang YM, Song YL (2016) Knockdown of long noncoding RNA AB073614 inhibits glioma cell proliferation and migration via affecting epithelial-mesenchymal transition. Eur Rev Medical Pharmacol Sci 20:3997–4002

  38. 38.

    Zeng J, Du T, Song Y, Gao Y, Li F, Wu R, Chen Y, Li W, Zhou H, Yang Y, Pei Z (2016) Knockdown of long noncoding RNA CCAT2 inhibits cellular proliferation, invasion, and EMT in glioma cells. Oncol Res 25:913–921. https://doi.org/10.3727/096504016x14792098307036

  39. 39.

    Ke J, Yao YL, Zheng J, Wang P, Liu YH, Ma J, Li Z, Liu XB, Li ZQ, Wang ZH, Xue YX (2015) Knockdown of long non-coding RNA HOTAIR inhibits malignant biological behaviors of human glioma cells via modulation of miR-326. Oncotarget 6:21934–21949. https://doi.org/10.18632/oncotarget.4290

  40. 40.

    Liu H, Lv Z, Guo E (2015) Knockdown of long noncoding RNA SPRY4-IT1 suppresses glioma cell proliferation, metastasis and epithelial-mesenchymal transition. Int J Clin Exp Pathol 8:9140–9146

  41. 41.

    Yao Y, Ma J, Xue Y, Wang P, Li Z, Liu J, Chen L, Xi Z, Teng H, Wang Z, Li Z, Liu Y (2015) Knockdown of long non-coding RNA XIST exerts tumor-suppressive functions in human glioblastoma stem cells by up-regulating miR-152. Cancer Lett 359:75–86. https://doi.org/10.1016/j.canlet.2014.12.051

Download references


This study was supported by the Key Research and Development Project from the Department of Science and Technology of Sichuan Province, China (grant number 2017SZ0006). The sponsor had no role in the design or conduct of this research.

Author information

Study design: Yanhui Liu, Junhong Li, Ruofei Liang.

Literature search: Ruofei Liang, Chen Song, Yufan Xiang.

Data collection: Junhong Li, Ruofei Liang.

Statistical analysis: Junhong Li, Yufan Xiang.

Result interpretation: Yanhui Liu, Junhong Li, Ruofei Liang.

Manuscript preparation: Junhong Li, Ruofei Liang.

Correspondence to Yanhui Liu.

Ethics declarations

Conflicts of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Li, J., Liang, R., Song, C. et al. Prognostic and clinicopathological significance of long non-coding RNA in glioma. Neurosurg Rev 43, 1–8 (2020). https://doi.org/10.1007/s10143-018-0965-x

Download citation


  • Long non-coding RNA
  • Glioma
  • Prognosis
  • Characteristic features