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Published in: Journal of Cancer Research and Clinical Oncology 12/2015

01-12-2015 | Original Article – Cancer Research

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

Authors: Gaoxiang Ma, Qiaoyan Wang, Chunye Lv, Fulin Qiang, Qiuhan Hua, Haiyan Chu, Mulong Du, Na Tong, Yejuan Jiang, Meilin Wang, Zhengdong Zhang, Jian Wang, Weida Gong

Published in: Journal of Cancer Research and Clinical Oncology | Issue 12/2015

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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.
Appendix
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Literature
go back to reference 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):3185–3193PubMed 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):3185–3193PubMed
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
go back to reference 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):764–774PubMedCentralCrossRefPubMed 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):764–774PubMedCentralCrossRefPubMed
go back to reference 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 PubMedCentralCrossRefPubMed 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 PubMedCentralCrossRefPubMed
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
go back to reference 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 PubMedCentralCrossRefPubMed 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 PubMedCentralCrossRefPubMed
go back to reference 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 PubMedCentralCrossRefPubMed 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 PubMedCentralCrossRefPubMed
go back to reference 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):1456–1466CrossRefPubMed 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):1456–1466CrossRefPubMed
go back to reference 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 PubMed 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 PubMed
go back to reference 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 PubMedCentralCrossRefPubMed 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 PubMedCentralCrossRefPubMed
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
go back to reference 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 PubMedCentralCrossRefPubMed 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 PubMedCentralCrossRefPubMed
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
go back to reference 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 PubMedCentralCrossRefPubMed 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 PubMedCentralCrossRefPubMed
Metadata
Title
The prognostic significance of HOTAIR for predicting clinical outcome in patients with digestive system tumors
Authors
Gaoxiang Ma
Qiaoyan Wang
Chunye Lv
Fulin Qiang
Qiuhan Hua
Haiyan Chu
Mulong Du
Na Tong
Yejuan Jiang
Meilin Wang
Zhengdong Zhang
Jian Wang
Weida Gong
Publication date
01-12-2015
Publisher
Springer Berlin Heidelberg
Published in
Journal of Cancer Research and Clinical Oncology / Issue 12/2015
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-015-1980-8

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