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Published in: Tumor Biology 5/2016

01-05-2016 | Original Article

Circulating long noncoding RNA GAS5 as a potential biomarker in breast cancer for assessing the surgical effects

Authors: Lu Han, Pei Ma, Song-Mei Liu, Xin Zhou

Published in: Tumor Biology | Issue 5/2016

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Abstract

Long noncoding RNAs (lncRNAs) play a vital role in tumorigenesis. Until now, the value of circulating lncRNAs in the diagnosis of breast cancer (BC) has remained unknown. Here, we have explored the clinical significance of lncRNAs GAS5 and H19 in BC patients. Total RNA in the plasma was extracted from 90 preoperative BC patients, 39 postoperative BC patients, and 76 healthy controls. The expression levels were measured by quantitative real-time PCR. The potential associations between GAS5, H19 levels, and patients’ clinical characteristics were analyzed. No significant differences were found between the BC patients and the healthy controls in the expression levels of GAS5 (P = 0.441) and H19 (P = 0.554), normalized by GAPDH. Plasma GAS5 exhibited correlations with the Ki67 proliferation index in 90 preoperative BC patients (P = 0.012). Compared with paired preoperative plasma, the postoperative levels of GAS5 and H19 significantly decreased in 71.8 % of BC patients (28/39) and 82.1 % of BC patients (32/39), respectively. Analysis in the 39 paired preoperative and postoperative plasma samples showed that lower GAS5 levels appeared in the patients with a high Ki67 proliferation index before surgery (P = 0.012) and the patients with a positive lymph node metastasis state after surgery (P = 0.029). Plasma lncRNA GAS5 may have the potential to assess the surgical effects and prognosis for BC patients.
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Literature
1.
go back to reference Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–86.CrossRefPubMed Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–86.CrossRefPubMed
2.
go back to reference Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009;151:716–726, 236. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009;151:716–726, 236.
3.
go back to reference Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–8.CrossRefPubMed Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–8.CrossRefPubMed
5.
go back to reference Li P, Xie XB, Chen Q, Pang GL, Luo W, Tu JC, et al. MiRNA-15a mediates cell cycle arrest and potentiates apoptosis in breast cancer cells by targeting synuclein-gamma. Asian Pac J Cancer Prev. 2014;15:6949–54.CrossRefPubMed Li P, Xie XB, Chen Q, Pang GL, Luo W, Tu JC, et al. MiRNA-15a mediates cell cycle arrest and potentiates apoptosis in breast cancer cells by targeting synuclein-gamma. Asian Pac J Cancer Prev. 2014;15:6949–54.CrossRefPubMed
6.
go back to reference Qi JH, Wang J, Chen J, Shen F, Huang JT, Sen S, et al. High-resolution melting analysis reveals genetic polymorphisms in microRNAs confer hepatocellular carcinoma risk in Chinese patients. BMC Cancer. 2014;14:643.CrossRefPubMedPubMedCentral Qi JH, Wang J, Chen J, Shen F, Huang JT, Sen S, et al. High-resolution melting analysis reveals genetic polymorphisms in microRNAs confer hepatocellular carcinoma risk in Chinese patients. BMC Cancer. 2014;14:643.CrossRefPubMedPubMedCentral
7.
go back to reference Wang J, Zhang KY, Liu SM, Sen S. Tumor-associated circulating microRNAs as biomarkers of cancer. Molecules. 2014;19:1912–38.CrossRefPubMed Wang J, Zhang KY, Liu SM, Sen S. Tumor-associated circulating microRNAs as biomarkers of cancer. Molecules. 2014;19:1912–38.CrossRefPubMed
8.
go back to reference Inns J., James V. Circulating microRNAs for the prediction of metastasis in breast cancer patients diagnosed with early stage disease. Breast. 2015. Inns J., James V. Circulating microRNAs for the prediction of metastasis in breast cancer patients diagnosed with early stage disease. Breast. 2015.
9.
go back to reference Wozniak MB, Scelo G, Muller DC, Mukeria A, Zaridze D, Brennan P. Circulating microRNAs as non-invasive biomarkers for early detection of non-small-cell lung cancer. PLoS One. 2015;10, e125026.CrossRef Wozniak MB, Scelo G, Muller DC, Mukeria A, Zaridze D, Brennan P. Circulating microRNAs as non-invasive biomarkers for early detection of non-small-cell lung cancer. PLoS One. 2015;10, e125026.CrossRef
10.
go back to reference Qi J, Wang J, Katayama H, Sen S, Liu SM. Circulating microRNAs (cmiRNAs) as novel potential biomarkers for hepatocellular carcinoma. Neoplasma. 2013;60:135–42.CrossRefPubMedPubMedCentral Qi J, Wang J, Katayama H, Sen S, Liu SM. Circulating microRNAs (cmiRNAs) as novel potential biomarkers for hepatocellular carcinoma. Neoplasma. 2013;60:135–42.CrossRefPubMedPubMedCentral
11.
go back to reference Huang JT, Liu SM, Ma H, Yang Y, Zhang X, Sun H, et al. Systematic review and meta-analysis: circulating miRNAs for diagnosis of hepatocellular carcinoma. J Cell Physiol. 2015. Huang JT, Liu SM, Ma H, Yang Y, Zhang X, Sun H, et al. Systematic review and meta-analysis: circulating miRNAs for diagnosis of hepatocellular carcinoma. J Cell Physiol. 2015.
12.
go back to reference Brunner AL, Beck AH, Edris B, Sweeney RT, Zhu SX, Li R, et al. Transcriptional profiling of long non-coding RNAs and novel transcribed regions across a diverse panel of archived human cancers. Genome Biol. 2012;13:R75.CrossRefPubMedPubMedCentral Brunner AL, Beck AH, Edris B, Sweeney RT, Zhu SX, Li R, et al. Transcriptional profiling of long non-coding RNAs and novel transcribed regions across a diverse panel of archived human cancers. Genome Biol. 2012;13:R75.CrossRefPubMedPubMedCentral
13.
15.
go back to reference Crea F, Watahiki A, Quagliata L, Xue H, Pikor L, Parolia A, et al. Identification of a long non-coding RNA as a novel biomarker and potential therapeutic target for metastatic prostate cancer. Oncotarget. 2014;5:764–74.CrossRefPubMedPubMedCentral Crea F, Watahiki A, Quagliata L, Xue H, Pikor L, Parolia A, et al. Identification of a long non-coding RNA as a novel biomarker and potential therapeutic target for metastatic prostate cancer. Oncotarget. 2014;5:764–74.CrossRefPubMedPubMedCentral
16.
go back to reference Dong L, Qi P, Xu MD, Ni SJ, Huang D, Xu QH, et al. Circulating CUDR, LSINCT-5 and PTENP1 long noncoding RNAs in sera distinguish patients with gastric cancer from healthy controls. Int J Cancer. 2015. Dong L, Qi P, Xu MD, Ni SJ, Huang D, Xu QH, et al. Circulating CUDR, LSINCT-5 and PTENP1 long noncoding RNAs in sera distinguish patients with gastric cancer from healthy controls. Int J Cancer. 2015.
17.
go back to reference Tong YS, Wang XW, Zhou XL, Liu ZH, Yang TX, Shi WH, et al. Identification of the long non-coding RNA POU3F3 in plasma as a novel biomarker for diagnosis of esophageal squamous cell carcinoma. Mol Cancer. 2015;14:3.CrossRefPubMedPubMedCentral Tong YS, Wang XW, Zhou XL, Liu ZH, Yang TX, Shi WH, et al. Identification of the long non-coding RNA POU3F3 in plasma as a novel biomarker for diagnosis of esophageal squamous cell carcinoma. Mol Cancer. 2015;14:3.CrossRefPubMedPubMedCentral
18.
go back to reference Zhou X, Yin C, Dang Y, Ye F, Zhang G. Identification of the long non-coding RNA H19 in plasma as a novel biomarker for diagnosis of gastric cancer. Sci Rep. 2015;5:11516.CrossRefPubMedPubMedCentral Zhou X, Yin C, Dang Y, Ye F, Zhang G. Identification of the long non-coding RNA H19 in plasma as a novel biomarker for diagnosis of gastric cancer. Sci Rep. 2015;5:11516.CrossRefPubMedPubMedCentral
19.
go back to reference Chen G, Wang Z, Wang D, Qiu C, Liu M, Chen X, et al. LncRNADisease: a database for long-non-coding RNA-associated diseases. Nucleic Acids Res. 2013;41:D983–6.CrossRefPubMed Chen G, Wang Z, Wang D, Qiu C, Liu M, Chen X, et al. LncRNADisease: a database for long-non-coding RNA-associated diseases. Nucleic Acids Res. 2013;41:D983–6.CrossRefPubMed
20.
go back to reference Shao Y, Ye M, Jiang X, Sun W, Ding X, Liu Z, et al. Gastric juice long noncoding RNA used as a tumor marker for screening gastric cancer. Cancer. 2014;120:3320–8.CrossRefPubMed Shao Y, Ye M, Jiang X, Sun W, Ding X, Liu Z, et al. Gastric juice long noncoding RNA used as a tumor marker for screening gastric cancer. Cancer. 2014;120:3320–8.CrossRefPubMed
21.
22.
go back to reference Ng SY, Lin L, Soh BS, Stanton LW. Long noncoding RNAs in development and disease of the central nervous system. Trends Genet. 2013;29:461–8.CrossRefPubMed Ng SY, Lin L, Soh BS, Stanton LW. Long noncoding RNAs in development and disease of the central nervous system. Trends Genet. 2013;29:461–8.CrossRefPubMed
24.
go back to reference Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464:1071–6.CrossRefPubMedPubMedCentral Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464:1071–6.CrossRefPubMedPubMedCentral
25.
go back to reference Pickard MR, Williams GT. Regulation of apoptosis by long non-coding RNA GAS5 in breast cancer cells: implications for chemotherapy. Breast Cancer Res Treat. 2014;145:359–70.CrossRefPubMed Pickard MR, Williams GT. Regulation of apoptosis by long non-coding RNA GAS5 in breast cancer cells: implications for chemotherapy. Breast Cancer Res Treat. 2014;145:359–70.CrossRefPubMed
26.
go back to reference Lottin S, Adriaenssens E, Dupressoir T, Berteaux N, Montpellier C, Coll J, et al. Overexpression of an ectopic H19 gene enhances the tumorigenic properties of breast cancer cells. Carcinogenesis. 2002;23:1885–95.CrossRefPubMed Lottin S, Adriaenssens E, Dupressoir T, Berteaux N, Montpellier C, Coll J, et al. Overexpression of an ectopic H19 gene enhances the tumorigenic properties of breast cancer cells. Carcinogenesis. 2002;23:1885–95.CrossRefPubMed
27.
go back to reference Silva JM, Boczek NJ, Berres MW, Ma X, Smith DI. LSINCT5 is over expressed in breast and ovarian cancer and affects cellular proliferation. RNA Biol. 2011;8:496–505.CrossRefPubMed Silva JM, Boczek NJ, Berres MW, Ma X, Smith DI. LSINCT5 is over expressed in breast and ovarian cancer and affects cellular proliferation. RNA Biol. 2011;8:496–505.CrossRefPubMed
28.
go back to reference Shi Y, Lu J, Zhou J, Tan X, He Y, Ding J, et al. Long non-coding RNA Loc554202 regulates proliferation and migration in breast cancer cells. Biochem Biophys Res Commun. 2014;446:448–53.CrossRefPubMed Shi Y, Lu J, Zhou J, Tan X, He Y, Ding J, et al. Long non-coding RNA Loc554202 regulates proliferation and migration in breast cancer cells. Biochem Biophys Res Commun. 2014;446:448–53.CrossRefPubMed
29.
go back to reference Godinho MF, Sieuwerts AM, Look MP, Meijer D, Foekens JA, Dorssers LC, et al. Relevance of BCAR4 in tamoxifen resistance and tumour aggressiveness of human breast cancer. Br J Cancer. 2010;103:1284–91.CrossRefPubMedPubMedCentral Godinho MF, Sieuwerts AM, Look MP, Meijer D, Foekens JA, Dorssers LC, et al. Relevance of BCAR4 in tamoxifen resistance and tumour aggressiveness of human breast cancer. Br J Cancer. 2010;103:1284–91.CrossRefPubMedPubMedCentral
30.
go back to reference Mourtada-Maarabouni M, Pickard MR, Hedge VL, Farzaneh F, Williams GT. GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer. Oncogene. 2009;28:195–208.CrossRefPubMed Mourtada-Maarabouni M, Pickard MR, Hedge VL, Farzaneh F, Williams GT. GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer. Oncogene. 2009;28:195–208.CrossRefPubMed
31.
go back to reference Matouk IJ, DeGroot N, Mezan S, Ayesh S, Abu-lail R, Hochberg A, et al. The H19 non-coding RNA is essential for human tumor growth. PLoS One. 2007;2, e845.CrossRefPubMedPubMedCentral Matouk IJ, DeGroot N, Mezan S, Ayesh S, Abu-lail R, Hochberg A, et al. The H19 non-coding RNA is essential for human tumor growth. PLoS One. 2007;2, e845.CrossRefPubMedPubMedCentral
32.
go back to reference Sun M, Jin FY, Xia R, Kong R, Li JH, Xu TP, et al. Decreased expression of long noncoding RNA GAS5 indicates a poor prognosis and promotes cell proliferation in gastric cancer. BMC Cancer. 2014;14:319.CrossRefPubMedPubMedCentral Sun M, Jin FY, Xia R, Kong R, Li JH, Xu TP, et al. Decreased expression of long noncoding RNA GAS5 indicates a poor prognosis and promotes cell proliferation in gastric cancer. BMC Cancer. 2014;14:319.CrossRefPubMedPubMedCentral
33.
go back to reference Shi X, Sun M, Liu H, Yao Y, Kong R, Chen F, et al. A critical role for the long non-coding RNA GAS5 in proliferation and apoptosis in non-small-cell lung cancer. Mol Carcinog. 2015;54 Suppl 1:E1–12.CrossRefPubMed Shi X, Sun M, Liu H, Yao Y, Kong R, Chen F, et al. A critical role for the long non-coding RNA GAS5 in proliferation and apoptosis in non-small-cell lung cancer. Mol Carcinog. 2015;54 Suppl 1:E1–12.CrossRefPubMed
34.
go back to reference Li H, Yu B, Li J, Su L, Yan M, Zhu Z, et al. Overexpression of lncRNA H19 enhances carcinogenesis and metastasis of gastric cancer. Oncotarget. 2014;5:2318–29.CrossRefPubMedPubMedCentral Li H, Yu B, Li J, Su L, Yan M, Zhu Z, et al. Overexpression of lncRNA H19 enhances carcinogenesis and metastasis of gastric cancer. Oncotarget. 2014;5:2318–29.CrossRefPubMedPubMedCentral
35.
go back to reference Quek XC, Thomson DW, Maag JL, Bartonicek N, Signal B, Clark MB, et al. LncRNAdb v2.0: expanding the reference database for functional long noncoding RNAs. Nucleic Acids Res. 2015;43:D168–73.CrossRefPubMed Quek XC, Thomson DW, Maag JL, Bartonicek N, Signal B, Clark MB, et al. LncRNAdb v2.0: expanding the reference database for functional long noncoding RNAs. Nucleic Acids Res. 2015;43:D168–73.CrossRefPubMed
36.
go back to reference Ahlin C, Aaltonen K, Amini RM, Nevanlinna H, Fjallskog ML, Blomqvist C. Ki67 and cyclin a as prognostic factors in early breast cancer. What are the optimal cut-off values? Histopathology. 2007;51:491–8.CrossRefPubMed Ahlin C, Aaltonen K, Amini RM, Nevanlinna H, Fjallskog ML, Blomqvist C. Ki67 and cyclin a as prognostic factors in early breast cancer. What are the optimal cut-off values? Histopathology. 2007;51:491–8.CrossRefPubMed
37.
go back to reference Mu K, Li L, Yang Q, Yun H, Kharaziha P, Ye DW, et al. A standardized method for quantifying proliferation by Ki-67 and cyclin A immunohistochemistry in breast cancer. Ann Diagn Pathol. 2015. Mu K, Li L, Yang Q, Yun H, Kharaziha P, Ye DW, et al. A standardized method for quantifying proliferation by Ki-67 and cyclin A immunohistochemistry in breast cancer. Ann Diagn Pathol. 2015.
38.
go back to reference Liu Z, Shao Y, Tan L, Shi H, Chen S, Guo J. Clinical significance of the low expression of FER1L4 in gastric cancer patients. Tumour Biol. 2014;35:9613–7.CrossRefPubMed Liu Z, Shao Y, Tan L, Shi H, Chen S, Guo J. Clinical significance of the low expression of FER1L4 in gastric cancer patients. Tumour Biol. 2014;35:9613–7.CrossRefPubMed
Metadata
Title
Circulating long noncoding RNA GAS5 as a potential biomarker in breast cancer for assessing the surgical effects
Authors
Lu Han
Pei Ma
Song-Mei Liu
Xin Zhou
Publication date
01-05-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 5/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4568-7

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