Skip to main content

Advertisement

SpringerLink
Log in

The prognostic significance of HOTAIR for predicting clinical outcome in patients with digestive system tumors

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Although some studies have assessed the prognostic value of HOTAIR in patients with digestive system tumors, the relationship between the HOTAIR and outcome of digestive system tumors remains unknown.

Methods

The PubMed was searched to identify the eligible studies. Here, we performed a meta-analysis with 11 studies, including a total of 903 cases. Pooled hazard ratios (HRs) and 95 % confidence interval (CI) of HOTAIR for cancer survival were calculated.

Results

We found that the pooled HR elevated HOTAIR expression in tumor tissues was 2.36 (95 % CI 1.88–2.97) compared with patients with low HOTAIR expression. Moreover, subgroup analysis revealed that HOTAIR overexpression was also markedly associated with short survival for esophageal squamous cell carcinoma (HR 2.19, 95 % CI 1.62–2.94) and gastric cancer (HR 1.66, 95 % CI 1.02–2.68). In addition, up-regulated HOTAIR was significantly related to survival of digestive system cancer among the studies with more follow-up time (follow time ≥ 5 years) (HR 2.51, 95 % CI 1.99–3.17). When stratified by HR resource and number of patients, the result indicated consistent results with the overall analysis. Subgroup analysis on ethnicities did not change the prognostic influence of elevated HOTAIR expression. Additionally, we conducted an independent validation cohort including 71 gastric cancer cases, in which patients with up-regulated HOTAIR expression had an unfavorable outcome with HR of 2.10 (95 % CI 1.10–4.03).

Conclusion

The results suggest that aberrant HOTAIR expression may serve as a candidate positive marker to predict the prognosis of patients with carcinoma of digestive system.

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

  • Arita T, Ichikawa D, Konishi H, Komatsu S, Shiozaki A, Shoda K, Kawaguchi T, Hirajima S, Nagata H, Kubota T, Fujiwara H, Okamoto K, Otsuji E (2013) Circulating long non-coding RNAs in plasma of patients with gastric cancer. Anticancer Res 33(8):3185–3193

    CAS  PubMed  Google Scholar 

  • Chen FJ, Sun M, Li SQ, Wu QQ, Ji L, Liu ZL, Zhou GZ, Cao G, Jin L, Xie HW, Wang CM, Lv J, De W, Wu M, Cao XF (2013) Upregulation of the long non-coding RNA HOTAIR promotes esophageal squamous cell carcinoma metastasis and poor prognosis. Mol Carcinog 52(11):908–915. doi:10.1002/mc.21944

    Article  CAS  PubMed  Google Scholar 

  • Crea F, Watahiki A, Quagliata L, Xue H, Pikor L, Parolia A, Wang Y, Lin D, Lam WL, Farrar WL, Isogai T, Morant R, Castori-Eppenberger S, Chi KN, Helgason CD (2014) Identification of a long non-coding RNA as a novel biomarker and potential therapeutic target for metastatic prostate cancer. Oncotarget 5(3):764–774

    Article  PubMed Central  PubMed  Google Scholar 

  • de Graeff P, Crijns AP, de Jong S, Boezen M, Post WJ, de Vries EG, van der Zee AG, de Bock GH (2009) Modest effect of p53, EGFR and HER-2/neu on prognosis in epithelial ovarian cancer: a meta-analysis. Br J Cancer 101(1):149–159. doi:10.1038/sj.bjc.6605112

    Article  PubMed Central  PubMed  Google Scholar 

  • Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Endo H, Shiroki T, Nakagawa T, Yokoyama M, Tamai K, Yamanami H, Fujiya T, Sato I, Yamaguchi K, Tanaka N, Iijima K, Shimosegawa T, Sugamura K, Satoh K (2013) Enhanced expression of long non-coding RNA HOTAIR is associated with the development of gastric cancer. PLoS One 8(10):e77070. doi:10.1371/journal.pone.0077070

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fu X, Han Y, Wu Y, Zhu X, Lu X, Mao F, Wang X, He X, Zhao Y (2011) Prognostic role of microRNA-21 in various carcinomas: a systematic review and meta-analysis. Eur J Clin Invest 41(11):1245–1253. doi:10.1111/j.1365-2362.2011.02535.x

    Article  CAS  PubMed  Google Scholar 

  • Ge XS, Ma HJ, Zheng XH, Ruan HL, Liao XY, Xue WQ, Chen YB, Zhang Y, Jia WH (2013) HOTAIR, a prognostic factor in esophageal squamous cell carcinoma, inhibits WIF-1 expression and activates Wnt pathway. Cancer Sci 104(12):1675–1682. doi:10.1111/cas.12296

    Article  CAS  PubMed  Google Scholar 

  • Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL, Wang Y, Brzoska P, Kong B, Li R, West RB, van de Vijver MJ, Sukumar S, Chang HY (2010) Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464(7291):1071–1076. doi:10.1038/nature08975

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, Cabili MN, Jaenisch R, Mikkelsen TS, Jacks T, Hacohen N, Bernstein BE, Kellis M, Regev A, Rinn JL, Lander ES (2009) Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458(7235):223–227. doi:10.1038/nature07672

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hayes DF, Bast RC, Desch CE, Fritsche H Jr, Kemeny NE, Jessup JM, Locker GY, Macdonald JS, Mennel RG, Norton L, Ravdin P, Taube S, Winn RJ (1996) Tumor marker utility grading system: a framework to evaluate clinical utility of tumor markers. J Natl Cancer Inst 88(20):1456–1466

    Article  CAS  PubMed  Google Scholar 

  • Ishibashi M, Kogo R, Shibata K, Sawada G, Takahashi Y, Kurashige J, Akiyoshi S, Sasaki S, Iwaya T, Sudo T, Sugimachi K, Mimori K, Wakabayashi G, Mori M (2013) Clinical significance of the expression of long non-coding RNA HOTAIR in primary hepatocellular carcinoma. Oncol Rep 29(3):946–950. doi:10.3892/or.2012.2219

    CAS  PubMed  Google Scholar 

  • Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ (2008) Cancer statistics, 2008. CA Cancer J Clin 58(2):71–96. doi:10.3322/CA.2007.0010

    Article  PubMed  Google Scholar 

  • Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D, Thomas K, Presser A, Bernstein BE, van Oudenaarden A, Regev A, Lander ES, Rinn JL (2009) Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci USA 106(28):11667–11672. doi:10.1073/pnas.0904715106

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kim K, Jutooru I, Chadalapaka G, Johnson G, Frank J, Burghardt R, Kim S, Safe S (2013) HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer. Oncogene 32(13):1616–1625. doi:10.1038/onc.2012.193

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kogo R, Shimamura T, Mimori K, Kawahara K, Imoto S, Sudo T, Tanaka F, Shibata K, Suzuki A, Komune S, Miyano S, Mori M (2011) Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res 71(20):6320–6326. doi:10.1158/0008-5472.CAN-11-1021

    Article  CAS  PubMed  Google Scholar 

  • Li X, Zhang Y, Ding J, Wu K, Fan D (2010) Survival prediction of gastric cancer by a seven-microRNA signature. Gut 59(5):579–585. doi:10.1136/gut.2008.175497

    Article  CAS  PubMed  Google Scholar 

  • Li X, Wu Z, Mei Q, Guo M, Fu X, Han W (2013) Long non-coding RNA HOTAIR, a driver of malignancy, predicts negative prognosis and exhibits oncogenic activity in oesophageal squamous cell carcinoma. Br J Cancer 109(8):2266–2278. doi:10.1038/bjc.2013.548

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Liu XH, Sun M, Nie FQ, Ge YB, Zhang EB, Yin DD, Kong R, Xia R, Lu KH, Li JH, De W, Wang KM, Wang ZX (2014) Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer. Mol cancer 13:92. doi:10.1186/1476-4598-13-92

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lv XB, Lian GY, Wang HR, Song E, Yao H, Wang MH (2013) Long noncoding RNA HOTAIR is a prognostic marker for esophageal squamous cell carcinoma progression and survival. PLoS One 8(5):e63516. doi:10.1371/journal.pone.0063516

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM (2005) REporting recommendations for tumour MARKer prognostic studies (REMARK). Br J Cancer 93(4):387–391. doi:10.1038/sj.bjc.6602678

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nagini S (2012) Carcinoma of the stomach: a review of epidemiology, pathogenesis, molecular genetics and chemoprevention. World J Gastrointest Oncol 4(7):156–169. doi:10.4251/wjgo.v4.i7.156

    Article  PubMed Central  PubMed  Google Scholar 

  • 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 

  • Qi YJ, Chao WX, Chiu JF (2012) An overview of esophageal squamous cell carcinoma proteomics. J Proteom 75(11):3129–3137. doi:10.1016/j.jprot.2012.04.025

    Article  CAS  Google Scholar 

  • Ren S, Wang F, Shen J, Sun Y, Xu W, Lu J, Wei M, Xu C, Wu C, Zhang Z, Gao X, Liu Z, Hou J, Huang J (2013) Long non-coding RNA metastasis associated in lung adenocarcinoma transcript 1 derived miniRNA as a novel plasma-based biomarker for diagnosing prostate cancer. Eur J Cancer 49(13):2949–2959. doi:10.1016/j.ejca.2013.04.026

    Article  CAS  PubMed  Google Scholar 

  • Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, Goodnough LH, Helms JA, Farnham PJ, Segal E, Chang HY (2007) Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129(7):1311–1323. doi:10.1016/j.cell.2007.05.022

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Spizzo R, Almeida MI, Colombatti A, Calin GA (2012) Long non-coding RNAs and cancer: a new frontier of translational research? Oncogene 31(43):4577–4587. doi:10.1038/onc.2011.621

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Xia X, Yang B, Zhai X, Liu X, Shen K, Wu Z, Cai J (2013) Prognostic role of microRNA-21 in colorectal cancer: a meta-analysis. PLoS One 8(11):e80426. doi:10.1371/journal.pone.0080426

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Xie H, Ma H, Zhou D (2013) Plasma HULC as a promising novel biomarker for the detection of hepatocellular carcinoma. BioMed Res Int 2013:136106. doi:10.1155/2013/136106

    PubMed Central  PubMed  Google Scholar 

  • Xu ZY, Yu QM, Du YA, Yang LT, Dong RZ, Huang L, Yu PF, Cheng XD (2013) Knockdown of long non-coding RNA HOTAIR suppresses tumor invasion and reverses epithelial–mesenchymal transition in gastric cancer. Int J Biol Sci 9(6):587–597. doi:10.7150/ijbs.6339

    Article  PubMed Central  PubMed  Google Scholar 

  • Zhang S, Chen S, Yang G, Gu F, Li M, Zhong B, Hu J, Hoffman A, Chen M (2014) Long noncoding RNA HOTAIR as an independent prognostic marker in cancer: a meta-analysis. PLoS One 9(8):e105538. doi:10.1371/journal.pone.0105538

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This study was partly supported by National Natural Science Foundation of China (81473050, 81473049 and 81230068), the Key Program for Basic Research of Jiangsu Provincial Department of Education (12KJA330002), Jiangsu Provincial Science and Technology Innovation Team, Collaborative Innovation Center For Cancer Personalized Medicine, and the Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine).

Conflict of interest

None.

Author information

Author notes

    Authors and Affiliations

    1. Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, 818 East Tianyuan Road, Jiangning District, Nanjing, 211166, China

      Gaoxiang Ma, Qiaoyan Wang, Qiuhan Hua, Haiyan Chu, Mulong Du, Na Tong, Meilin Wang & Zhengdong Zhang

    2. Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China

      Gaoxiang Ma, Qiaoyan Wang, Qiuhan Hua, Haiyan Chu, Mulong Du, Na Tong, Meilin Wang & Zhengdong Zhang

    3. Department of General Surgery, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China

      Chunye Lv

    4. Core Laboratory, Nantong Tumor Hospital, Nantong, China

      Fulin Qiang

    5. Department of General Surgery, Yixing Tumor Hospital, 45 East Dongshan Road, Yixing, Jiangsu Province, China

      Yejuan Jiang & Weida Gong

    6. Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Road 300, Nanjing, 210029, Jiangsu Province, China

      Jian Wang

    Authors
    1. Gaoxiang Ma
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Qiaoyan Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Chunye Lv
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Fulin Qiang
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Qiuhan Hua
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Haiyan Chu
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Mulong Du
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Na Tong
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Yejuan Jiang
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Meilin Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    11. Zhengdong Zhang
      View author publications

      You can also search for this author in PubMed Google Scholar

    12. Jian Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    13. Weida Gong
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Zhengdong Zhang, Jian Wang or Weida Gong.

    Additional information

    Gaoxiang Ma, Qiaoyan Wang and Chunye Lv have contributed equally to this work.

    Electronic supplementary material

    Below is the link to the electronic supplementary material.

    Supplementary material 1 (DOC 62 kb)

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Ma, G., Wang, Q., Lv, C. et al. The prognostic significance of HOTAIR for predicting clinical outcome in patients with digestive system tumors. J Cancer Res Clin Oncol 141, 2139–2145 (2015). https://doi.org/10.1007/s00432-015-1980-8

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s00432-015-1980-8

    Keywords

    Search

    Navigation