Skip to main content

Advertisement

SpringerLink
Log in

Long Noncoding RNA MALAT-1 Can Predict Metastasis and a Poor Prognosis: a Meta-Analysis

  • Original Article
  • Published:
Pathology & Oncology Research

Abstract

Elevated expression of MALAT-1 was found in various cancers, and correlated with metastasis and prognostic. This meta-analysis collected all relevant articles and explored correlation of MALAT-1 with lymph node metastasis (LNM), distant metastasis (DM), and overall survival (OS). A quantitative meta-analysis was performed through a systematic search in PubMed, Web of Science, Medline, CNKI, CBM, and the Cochrane Library. The odds ratios (OR) of LNM and DM and hazard ratio (HR) of OS were calculated to assess the association strength. Eight studies with a total of 845 patients were included in the meta-analysis. Six different types of cancer were evaluated, with 2 non-small cell lung cancer (NSCLC), 1 colorectal cancer (CRC), 1 gastric cancer (GC), 2 pancreatic cancer (PC), 1 clear cell renal cell carcinoma (ccRCC), and 1 osteosarcoma (OSA). Compared with low MALAT-1 expression, high MALAT-1 expression correlated with more LNM (OR = 2.08, 95 %CI: 1.00-4.32, p = 0.05) by a random-effects model (I 2 = 71 %, p = 0.004). A similar result was seen between MALAT-1 expression and DM, the OR was 3.52 (95 %CI: 1.06–11.71, p = 0.04) adopting a random-effects model (I 2 = 59 %, p = 0.04). Additionally, our analysis showed a poorer OS in patients with high MALAT-1 expression than those with low MALAT-1 expression (HR = 2.12, 95 %CI: 1.60–2.82, p < 0.001) adopting a random-effects model (I 2 = 56 %, p = 0.04). MALAT-1 may serve as a molecular marker for cancer metastasis and prognosis.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

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

Similar content being viewed by others

References

  1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2014) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. doi:10.1002/ijc.29210

    PubMed  Google Scholar 

  2. Pereira A, Perez-Medina T, Magrina JF, Magtibay PM, Rodriguez-Tapia A, de Leon J, Peregrin I, Ortiz-Quintana L (2014) Correlation between the extent of intraperitoneal disease and nodal metastasis in node-positive ovarian cancer patients. Eur J Surg Oncol 40(8):917–924. doi:10.1016/j.ejso.2014.04.001

    Article  CAS  PubMed  Google Scholar 

  3. Lee T, Tanaka H, Ohira M, Okita Y, Yoshii M, Sakurai K, Toyokawa T, Kubo N, Muguruma K, Tanaka S, Ohsawa M, Hirakawa K (2014) Clinical impact of the extent of lymph node micrometastasis in undifferentiated-type early gastric cancer. Oncology 86(4):244–252. doi:10.1159/000358803

    Article  PubMed  Google Scholar 

  4. Treilleux I, Arnedos M, Cropet C, Wang Q, Ferrero JM, Abadie-Lacourtoisie S, Levy C, Legouffe E, Lortholary A, Pujade-Lauraine E, Bourcier AV, Eymard JC, Spaeth D, Bachelot T (2014) Translational studies within the TAMRAD randomized GINECO trial: evidence for mTORC1 activation marker as a predictive factor for everolimus efficacy in advanced breast cancer. Ann Oncol. doi:10.1093/annonc/mdu497

    Google Scholar 

  5. Hu A, Huang JJ, Xu WH, Jin XJ, Li JP, Tang YJ, Huang XF, Cui HJ, Sun GB (2014) miR-21 and miR-375 microRNAs as candidate diagnostic biomarkers in squamous cell carcinoma of the larynx: association with patient survival. Am J Transl Res 6(5):604–613

    PubMed Central  CAS  PubMed  Google Scholar 

  6. Ponting CP, Oliver PL, Reik W (2009) Evolution and functions of long noncoding RNAs. Cell 136(4):629–641. doi:10.1016/j.cell.2009.02.006

    Article  CAS  PubMed  Google Scholar 

  7. Kaneko S, Li G, Son J, Xu CF, Margueron R, Neubert TA, Reinberg D (2010) Phosphorylation of the PRC2 component Ezh2 is cell cycle-regulated and up-regulates its binding to ncRNA. Genes Dev 24(23):2615–2620. doi:10.1101/gad.1983810

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, Shi Y, Segal E, Chang HY (2010) Long noncoding RNA as modular scaffold of histone modification complexes. Science 329(5992):689–693. doi:10.1126/science.1192002

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Wilusz JE, Sunwoo H, Spector DL (2009) Long noncoding RNAs: functional surprises from the RNA world. Genes Dev 23(13):1494–1504. doi:10.1101/gad.1800909

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Wang X, Song X, Glass CK, Rosenfeld MG (2011) The long arm of long noncoding RNAs: roles as sensors regulating gene transcriptional programs. Cold Spring Harb Perspect Biol 3(1):a003756. doi:10.1101/cshperspect.a003756

    Article  PubMed Central  PubMed  Google Scholar 

  11. Ji Q, Zhang L, Liu X, Zhou L, Wang W, Han Z, Sui H, Tang Y, Wang Y, Liu N, Ren J, Hou F, Li Q (2014) Long non-coding RNA MALAT1 promotes tumour growth and metastasis in colorectal cancer through binding to SFPQ and releasing oncogene PTBP2 from SFPQ/PTBP2 complex. Br J Cancer 111(4):736–748. doi:10.1038/bjc.2014.383

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Shen L, Chen L, Wang Y, Jiang X, Xia H, Zhuang Z (2014) Long noncoding RNA MALAT1 promotes brain metastasis by inducing epithelial-mesenchymal transition in lung cancer. J Neurooncol. doi:10.1007/s11060-014-1613-0

    Google Scholar 

  13. Cai B, Wu Z, Liao K, Zhang S (2014) Long noncoding RNA HOTAIR can serve as a common molecular marker for lymph node metastasis: a meta-analysis. Tumour Biol 35(9):8445–8450. doi:10.1007/s13277-014-2311-4

    Article  CAS  PubMed  Google Scholar 

  14. Akhbari P, Whitehouse A, Boyne JR (2014) Long noncoding RNAs drive metastatic progression in melanoma (Review). Int J Oncol 45(6):2181–2186. doi:10.3892/ijo.2014.2691

    PubMed  Google Scholar 

  15. Ji P, Diederichs S, Wang W, Boing S, Metzger R, Schneider PM, Tidow N, Brandt B, Buerger H, Bulk E, Thomas M, Berdel WE, Serve H, Muller-Tidow C (2003) MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene 22(39):8031–8041. doi:10.1038/sj.onc.1206928

    Article  PubMed  Google Scholar 

  16. Liu JH, Chen G, Dang YW, Li CJ, Luo DZ (2014) Expression and prognostic significance of lncRNA MALAT1 in pancreatic cancer tissues. Asian Pac J Cancer Prev 15(7):2971–2977

    Article  PubMed  Google Scholar 

  17. Xu C, Yang M, Tian J, Wang X, Li Z (2011) MALAT-1: a long non-coding RNA and its important 3′ end functional motif in colorectal cancer metastasis. Int J Oncol 39(1):169–175. doi:10.3892/ijo.2011.1007

    PubMed  Google Scholar 

  18. Tano K, Akimitsu N (2012) Long non-coding RNAs in cancer progression. Front Genet 3:219. doi:10.3389/fgene.2012.00219

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Eissmann M, Gutschner T, Hammerle M, Gunther S, Caudron-Herger M, Gross M, Schirmacher P, Rippe K, Braun T, Zornig M, Diederichs S (2012) Loss of the abundant nuclear non-coding RNA MALAT1 is compatible with life and development. RNA Biol 9(8):1076–1087. doi:10.4161/rna.21089

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. 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. doi:10.1186/1745-6215-8-16

    Article  PubMed Central  PubMed  Google Scholar 

  21. Zheng HT, Shi DB, Wang YW, Li XX, Xu Y, Tripathi P, Gu WL, Cai GX, Cai SJ (2014) High expression of lncRNA MALAT1 suggests a biomarker of poor prognosis in colorectal cancer. Int J Clin Exp Pathol 7(6):3174–3181

    PubMed Central  CAS  PubMed  Google Scholar 

  22. Zhang HM, Yang FQ, Chen SJ, Che J, Zheng JH (2014) Upregulation of long non-coding RNA MALAT1 correlates with tumor progression and poor prognosis in clear cell renal cell carcinoma. Tumour Biol. doi:10.1007/s13277-014-2925-6

    Google Scholar 

  23. Pang EJ, Yang R, Fu XB, Liu YF (2014) Overexpression of long non-coding RNA MALAT1 is correlated with clinical progression and unfavorable prognosis in pancreatic cancer. Tumour Biol. doi:10.1007/s13277-014-2850-8

    Google Scholar 

  24. Okugawa Y, Toiyama Y, Hur K, Toden S, Saigusa S, Tanaka K, Inoue Y, Mohri Y, Kusunoki M, Boland CR, Goel A (2014) Metastasis-associated long non-coding RNA drives gastric cancer development and promotes peritoneal metastasis. Carcinogenesis. doi:10.1093/carcin/bgu200

    PubMed  Google Scholar 

  25. Dong Y, Liang G, Yuan B, Yang C, Gao R, Zhou X (2014) MALAT1 promotes the proliferation and metastasis of osteosarcoma cells by activating the PI3K/Akt pathway. Tumour Biol. doi:10.1007/s13277-014-2631-4

    PubMed Central  Google Scholar 

  26. Schmidt LH, Spieker T, Koschmieder S, Schaffers S, Humberg J, Jungen D, Bulk E, Hascher A, Wittmer D, Marra A, Hillejan L, Wiebe K, Berdel WE, Wiewrodt R, Muller-Tidow C (2011) The long noncoding MALAT-1 RNA indicates a poor prognosis in non-small cell lung cancer and induces migration and tumor growth. J Thorac Oncol 6(12):1984–1992. doi:10.1097/JTO.0b013e3182307eac

    Article  PubMed  Google Scholar 

  27. Tripathi V, Ellis JD, Shen Z, Song DY, Pan Q, Watt AT, Freier SM, Bennett CF, Sharma A, Bubulya PA, Blencowe BJ, Prasanth SG, Prasanth KV (2010) The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol Cell 39(6):925–938. doi:10.1016/j.molcel.2010.08.011

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Yang L, Lin C, Liu W, Zhang J, Ohgi KA, Grinstein JD, Dorrestein PC, Rosenfeld MG (2011) ncRNA- and Pc2 methylation-dependent gene relocation between nuclear structures mediates gene activation programs. Cell 147(4):773–788. doi:10.1016/j.cell.2011.08.054

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Gutschner T, Hammerle M, Eissmann M, Hsu J, Kim Y, Hung G, Revenko A, Arun G, Stentrup M, Gross M, Zornig M, MacLeod AR, Spector DL, Diederichs S (2013) The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res 73(3):1180–1189. doi:10.1158/0008-5472.can-12-2850

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Hellerbrand C, Amann T, Schlegel J, Wild P, Bataille F, Spruss T, Hartmann A, Bosserhoff AK (2008) The novel gene MIA2 acts as a tumour suppressor in hepatocellular carcinoma. Gut 57(2):243–251. doi:10.1136/gut.2007.129544

    Article  CAS  PubMed  Google Scholar 

  31. Xu Y, Li WL, Fu L, Gu F, Ma YJ (2010) Slit2/Robo1 signaling in glioma migration and invasion. Neurosci Bull 26(6):474–478

    Article  PubMed  Google Scholar 

  32. Legg JA, Herbert JM, Clissold P, Bicknell R (2008) Slits and Roundabouts in cancer, tumour angiogenesis and endothelial cell migration. Angiogenesis 11(1):13–21. doi:10.1007/s10456-008-9100-x

    Article  PubMed  Google Scholar 

  33. Yiu GK, Kaunisto A, Chin YR, Toker A (2011) NFAT promotes carcinoma invasive migration through glypican-6. Biochem J 440(1):157–166. doi:10.1042/bj20110530

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Sekine Y, Demosky SJ, Stonik JA, Furuya Y, Koike H, Suzuki K, Remaley AT (2010) High-density lipoprotein induces proliferation and migration of human prostate androgen-independent cancer cells by an ABCA1-dependent mechanism. Mol Cancer Res 8(9):1284–1294. doi:10.1158/1541-7786.mcr-10-0008

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Toh B, Wang X, Keeble J, Sim WJ, Khoo K, Wong WC, Kato M, Prevost-Blondel A, Thiery JP, Abastado JP (2011) Mesenchymal transition and dissemination of cancer cells is driven by myeloid-derived suppressor cells infiltrating the primary tumor. PLoS Biol 9(9):e1001162. doi:10.1371/journal.pbio.1001162

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Gutschner T, Hammerle M, Diederichs S (2013) MALAT1—a paradigm for long noncoding RNA function in cancer. J Mol Med (Berl) 91(7):791–801. doi:10.1007/s00109-013-1028-y

    Article  CAS  Google Scholar 

  37. Wu XS, Wang XA, Wu WG, Hu YP, Li ML, Ding Q, Weng H, Shu YJ, Liu TY, Jiang L, Cao Y, Bao RF, Mu JS, Tan ZJ, Tao F, Liu YB (2014) MALAT1 promotes the proliferation and metastasis of gallbladder cancer cells by activating the ERK/MAPK pathway. Cancer Biol Ther 15(6):806–814. doi:10.4161/cbt.28584

    Article  PubMed Central  PubMed  Google Scholar 

  38. Li N, Wang HX, Zhang J, Ye YP, He GY (2012) KISS-1 inhibits the proliferation and invasion of gastric carcinoma cells. World J Gastroenterol 18(15):1827–1833. doi:10.3748/wjg.v18.i15.1827

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Hong SK, Yoon S, Moelling C, Arthan D, Park JI (2009) Noncatalytic function of ERK1/2 can promote Raf/MEK/ERK-mediated growth arrest signaling. J Biol Chem 284(48):33006–33018. doi:10.1074/jbc.M109.012591

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Xander P, Brito RR, Perez EC, Pozzibon JM, de Souza CF, Pellegrino R, Bernardo V, Jasiulionis MG, Mariano M, Lopes JD (2013) Crosstalk between B16 melanoma cells and B-1 lymphocytes induces global changes in tumor cell gene expression. Immunobiology 218(10):1293–1303. doi:10.1016/j.imbio.2013.04.017

    Article  CAS  PubMed  Google Scholar 

  41. Fan Y, Shen B, Tan M, Mu X, Qin Y, Zhang F, Liu Y (2014) TGF-beta-induced upregulation of malat1 promotes bladder cancer metastasis by associating with suz12. Clin Cancer Res 20(6):1531–1541. doi:10.1158/1078-0432.ccr-13-1455

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by grants from National Natural Science Foundation of China (grant no. 81272611). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Compliance with Ethical Standards

ᅟ

Conflict of Interests

All authors declare that there is no conflict of interests.

Author information

Authors and Affiliations

  1. Department of Oncology, Affiliated Hangzhou Hospital of Nanjing Medical University, No.261, huansha Road, shangcheng District, Hangzhou, 310006, People’s Republic of China

    Lucheng Zhu, Jihong Liu & Shenglin MA

  2. Department of Oncology, Hangzhou First People’s Hospital, No.261, huansha Road, shangcheng District, Hangzhou, 310006, People’s Republic of China

    Lucheng Zhu, Jihong Liu, Shenglin MA & Shirong Zhang

Authors
  1. Lucheng Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jihong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shenglin MA
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shirong Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Shenglin MA or Shirong Zhang.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhu, L., Liu, J., MA, S. et al. Long Noncoding RNA MALAT-1 Can Predict Metastasis and a Poor Prognosis: a Meta-Analysis. Pathol. Oncol. Res. 21, 1259–1264 (2015). https://doi.org/10.1007/s12253-015-9960-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12253-015-9960-5

Keywords

Search

Navigation