期刊论文详细信息
Journal of Experimental & Clinical Cancer Research
A four-long non-coding RNA signature in predicting breast cancer survival
Shen Fu2  Zhangru Yang1  Qing Zhang2  Ping Li1  Jin Meng1 
[1] Department of Radiation Oncology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yi Shan Rd, Shanghai 200233, China;Radiation Oncology Department, Shanghai Proton and Heavy Ion Center (SPHIC), 4365 Kang Xin Rd, Shanghai 201321, Pudong New District, China
关键词: Survival;    Gene signature;    Expression;    Biomarker;    Prognostic;    Breast cancer;    lncRNA;    Long non coding RNA;   
Others  :  1136113
DOI  :  10.1186/s13046-014-0084-7
 received in 2014-04-27, accepted in 2014-09-24,  发布年份 2014
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【 摘 要 】

Background

Many long non-coding RNAs(lncRNAs) have been found to be a good marker for several tumors. Using lncRNA-mining approach, we aimed to identify lncRNA expression signature that can predict breast cancer patient survival.

Methods

We performed LncRNA expression profiling in 887 breast cancer patients from Gene Expression Omnibus (GEO) datasets. The association between lncRNA signature and clinical survival was analyzed using the training set(n = 327, from GSE 20685). The validation for the association was performed in another three independent testing sets(252 from GSE21653, 204 from GSE12276, and 104 from GSE42568).

Results

A set of four lncRNA genes (U79277, AK024118, BC040204, AK000974) have been identified by the random survival forest algorithm. Using a risk score based on the expression signature of these lncRNAs, we separated the patients into low-risk and high-risk groups with significantly different survival times in the training set. This signature was validated in the other three cohorts. Further study revealed that the four-lncRNA expression signature was independent of age and subtype. Gene Set Enrichment Analysis (GSEA) suggested that gene sets were involved in several cancer metastasis related pathways.

Conclusions

These findings indicate that lncRNAs may be implicated in breast cancer pathogenesis. The four-lncRNA signature may have clinical implications in the selection of high-risk patients for adjuvant therapy.

【 授权许可】

   
2014 Meng et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Wahlestedt C: Targeting long non-coding RNA to therapeutically upregulate gene expression. Nat Rev Drug Discov 2013, 12:433-446.
  • [2]Beltran M, Puig I, Pena C, Garcia JM, Alvarez AB, Pena R, Bonilla F, de Herreros AG: A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition. Genes Dev 2008, 22:756-769.
  • [3]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: Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 2010, 464:1071-1076.
  • [4]Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, Goodnough LH, Helms JA, Farnham PJ, Segal E, Chang HY: Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 2007, 129:1311-1323.
  • [5]Viny AD, Clemente MJ, Jasek M, Askar M, Ishwaran H, Nowacki A, Zhang A, Maciejewski JP: MICA polymorphism identified by whole genome array associated with NKG2D-mediated cytotoxicity in T-cell large granular lymphocyte leukemia. Haematologica 2010, 95:1713-1721.
  • [6]Huarte M, Rinn JL: Large non-coding RNAs: missing links in cancer? Hum Mol Genet 2010, 19:R152-R161.
  • [7]Wapinski O, Chang HY: Long noncoding RNAs and human disease. Trends Cell Biol 2011, 21:354-361.
  • [8]Li L, Sun R, Liang Y, Pan X, Li Z, Bai P, Zeng X, Zhang D, Zhang L, Gao L: Association between polymorphisms in long non-coding RNA PRNCR1 in 8q24 and risk of colorectal cancer. J Exper Clin Can Res 2013, 32:104. BioMed Central Full Text
  • [9]Comprehensive molecular portraits of human breast tumours Nature 2012, 490:61-70.
  • [10]Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lønning PE, Børresen-Dale AL, Brown PO, Botstein D: Molecular portraits of human breast tumours. Nature 2000, 406:747-752.
  • [11]Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Lønning PE, Børresen-Dale AL: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 2001, 98:10869-10874.
  • [12]Paik S: Development and clinical utility of a 21-gene recurrence score prognostic assay in patients with early breast cancer treated with tamoxifen. Oncologist 2007, 12:631-635.
  • [13]Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, Baehner FL, Walker MG, Watson D, Park T, Hiller W, Fisher ER, Wickerham DL, Bryant J, Wolmark N: A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 2004, 351:2817-2826.
  • [14]Yin ZQ, Liu JJ, Xu YC, Yu J, Ding GH, Yang F, Tang L, Liu BH, Ma Y, Xia YW, Lin XL, Wang HX: A 41-gene signature derived from breast cancer stem cells as a predictor of survival. J Exper Clin Can Res 2014, 33:49. BioMed Central Full Text
  • [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, Müller-Tidow C: MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene 2003, 22:8031-8041.
  • [16]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: 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 2011, 6:1984-1992.
  • [17]Perez DS, Hoage TR, Pritchett JR, Ducharme-Smith AL, Halling ML, Ganapathiraju SC, Streng PS, Smith DI: Long, abundantly expressed non-coding transcripts are altered in cancer. Hum Mol Genet 2008, 17:642-655.
  • [18]Iacoangeli A, Lin Y, Morley EJ, Muslimov IA, Bianchi R, Reilly J, Weedon J, Diallo R, Bocker W, Tiedge H: BC200 RNA in invasive and preinvasive breast cancer. Carcinogenesis 2004, 25:2125-2133.
  • [19]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.
  • [20]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.
  • [21]Gibb EA, Vucic EA, Enfield KS, Stewart GL, Lonergan KM, Kennett JY, Becker-Santos DD, MacAulay CE, Lam S, Brown CJ, Lam WL: Human cancer long non-coding RNA transcriptomes. PLoS One 2011, 6:e25915.
  • [22]Risueno A, Fontanillo C, Dinger ME, de Las Rivas J: GATExplorer: genomic and transcriptomic explorer; mapping expression probes to gene loci, transcripts, exons and ncRNAs. BMC Bioinformatics 2010, 11:221. BioMed Central Full Text
  • [23]Liao Q, Xiao H, Bu D, Xie C, Miao R, Luo H, Zhao G, Yu K, Zhao H, Skogerbo G, Chen R, Wu Z, Liu C, Zhao Y: ncFANs: a web server for functional annotation of long non-coding RNAs. Nucleic Acids Res 2011, 39:W118-W124.
  • [24]Gellert P, Ponomareva Y, Braun T, Uchida S: Noncoder: a web interface for exon array-based detection of long non-coding RNAs. Nucleic Acids Res 2013, 41:e20.
  • [25]Du Z, Fei T, Verhaak RG, Su Z, Zhang Y, Brown M, Chen Y, Liu XS: Integrative genomic analyses reveal clinically relevant long noncoding RNAs in human cancer. Nat Struct Mol Biol 2013, 20:908-913.
  • [26]Zhang X, Sun S, Pu JK, Tsang AC, Lee D, Man VO, Lui WM, Wong ST, Leung GK: Long non-coding RNA expression profiles predict clinical phenotypes in glioma. Neurobiol Dis 2012, 48:1-8.
  • [27]Zhang XQ, Sun S, Lam KF, Kiang KM, Pu JK, Ho AS, Lui WM, Fung CF, Wong TS, Leung GK: A long non-coding RNA signature in glioblastoma multiforme predicts survival. Neurobiol Dis 2013, 58:123-131.
  • [28]Li J, Chen Z, Tian L, Zhou C, He MY, Gao Y, Wang S, Zhou F, Shi S, Feng X, Sun N, Liu Z, Skogerboe G, Dong J, Yao R, Zhao Y, Sun J, Zhang B, Yu Y, Shi X, Luo M, Shao K, Li N, Qiu B, Tan F, Chen R, He J: LncRNA profile study reveals a three-lncRNA signature associated with the survival of patients with oesophageal squamous cell carcinoma.Gut 2014, doi:10.1136/gutjnl-2013-305806. [Epub ahead of print].
  • [29]Kao KJ, Chang KM, Hsu HC, Huang AT: Correlation of microarray-based breast cancer molecular subtypes and clinical outcomes: implications for treatment optimization. BMC Cancer 2011, 11:143. BioMed Central Full Text
  • [30]Bos PD, Zhang XH, Nadal C, Shu W, Gomis RR, Nguyen DX, Minn AJ, van de Vijver MJ, Gerald WL, Foekens JA, Massague J: Genes that mediate breast cancer metastasis to the brain. Nature 2009, 459:1005-1009.
  • [31]Sabatier R, Finetti P, Cervera N, Lambaudie E, Esterni B, Mamessier E, Tallet A, Chabannon C, Extra JM, Jacquemier J, Viens P, Birnbaum D, Bertucci F, Viens P, Birnbaum D, Bertucci F: A gene expression signature identifies two prognostic subgroups of basal breast cancer. Breast Cancer Res Treat 2011, 126:407-420.
  • [32]Sabatier R, Finetti P, Adelaide J, Guille A, Borg JP, Chaffanet M, Lane L, Birnbaum D, Bertucci F: Down-regulation of ECRG4, a candidate tumor suppressor gene, in human breast cancer. PLoS One 2011, 6:e27656.
  • [33]Clarke C, Madden SF, Doolan P, Aherne ST, Joyce H, O’Driscoll L, Gallagher WM, Hennessy BT, Moriarty M, Crown J, Kennedy S, Clynes M: Correlating transcriptional networks to breast cancer survival: a large-scale coexpression analysis. Carcinogenesis 2013, 34(10):2300-2308.
  • [34]Pang KC, Stephen S, Engstrom PG, Tajul-Arifin K, Chen W, Wahlestedt C, Lenhard B, Hayashizaki Y, Mattick JS: RNAdb–a comprehensive mammalian noncoding RNA database. Nucleic Acids Res 2005, 33:D125-D130.
  • [35]Dinger ME, Pang KC, Mercer TR, Crowe ML, Grimmond SM, Mattick JS: NRED: a database of long noncoding RNA expression. Nucleic Acids Res 2009, 37:D122-D126.
  • [36]Sun L, Luo H, Bu D, Zhao G, Yu K, Zhang C, Liu Y, Chen R, Zhao Y: Utilizing sequence intrinsic composition to classify protein-coding and long non-coding transcripts. Nucleic Acids Res 2013, 41:e166.
  • [37]Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, Mesirov JP: Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A 2005, 102:15545-15550.
  • [38]Simon R, Lam A, Li MC, Ngan M, Menenzes S, Zhao Y: Analysis of gene expression data using BRB-ArrayTools. Cancer Inform 2007, 3:11-17.
  • [39]Ishwaran H, Kogalur UB: Consistency of random survival forests. Stat Probabil Lett 2010, 80:1056-1064.
  • [40]Kawaguchi A, Iwadate Y, Komohara Y, Sano M, Kajiwara K, Yajima N, Tsuchiya N, Homma J, Aoki H, Kobayashi T, Sakai Y, Hondoh H, Fujii Y, Kakuma T, Yamanaka R: Gene expression signature-based prognostic risk score in patients with primary central nervous system lymphoma. Clin Cancer Res 2012, 18:5672-5681.
  • [41]Alizadeh AA, Gentles AJ, Alencar AJ, Liu CL, Kohrt HE, Houot R, Goldstein MJ, Zhao S, Natkunam Y, Advani RH, Gascoyne RD, Briones J, Tibshirani RJ, Myklebust JH, Plevritis SK, Lossos IS, Levy R: Prediction of survival in diffuse large B-cell lymphoma based on the expression of 2 genes reflecting tumor and microenvironment. Blood 2011, 118:1350-1358.
  • [42]Bralten LB, French PJ: Genetic alterations in glioma. Cancers 2011, 3:1129-1140.
  • [43]Kang J, D’Andrea AD, Kozono D: A DNA repair pathway-focused score for prediction of outcomes in ovarian cancer treated with platinum-based chemotherapy. J Natl Cancer Inst 2012, 104:670-681.
  • [44]Kalluri R, Weinberg RA: The basics of epithelial-mesenchymal transition. J Clin Invest 2009, 119:1420-1428.
  • [45]Vogelstein B, Kinzler KW: Cancer genes and the pathways they control. Nat Med 2004, 10:789-799.
  • [46]Cui Z, Ren S, Lu J, Wang F, Xu W, Sun Y, Wei M, Chen J, Gao X, Xu C, Mao JH, Sun Y: The prostate cancer-up-regulated long noncoding RNA PlncRNA-1 modulates apoptosis and proliferation through reciprocal regulation of androgen receptor. Urol Oncol 2013, 31(7):1117-1123.
  • [47]Johnson R: Long non-coding RNAs in Huntington’s disease neurodegeneration. Neurobiol Dis 2012, 46:245-254.
  • [48]Michelhaugh SK, Lipovich L, Blythe J, Jia H, Kapatos G, Bannon MJ: Mining Affymetrix microarray data for long non-coding RNAs: altered expression in the nucleus accumbens of heroin abusers. J Neurochem 2011, 116:459-466.
  • [49]Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H, Guernec G, Martin D, Merkel A, Knowles DG, Lagarde J, Veeravalli L, Ruan X, Ruan Y, Lassmann T, Carninci P, Brown JB, Lipovich L, Gonzalez JM, Thomas M, Davis CA, Shiekhattar R, Gingeras TR, Hubbard TJ, Notredame C, Harrow J, Guigó R: The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res 2012, 22:1775-1789.
  • [50]Fachel AA, Tahira AC, Vilella-Arias SA, Maracaja-Coutinho V, Gimba ER, Vignal GM, Campos FS, Reis EM, Verjovski-Almeida S: Expression analysis and in silico characterization of intronic long noncoding RNAs in renal cell carcinoma: emerging functional associations. Mol Cancer 2013, 12:140. BioMed Central Full Text
  • [51]Schorderet P, Duboule D: Structural and functional differences in the long non-coding RNA hotair in mouse and human. PLoS Genet 2011, 7:e1002071.
  • [52]Altman DG, Royston P: The cost of dichotomising continuous variables. BMJ 2006, 332:1080.
  • [53]Winchester DP, Osteen RT, Menck HR: The National Cancer Data Base report on breast carcinoma characteristics and outcome in relation to age. Cancer 1996, 78:1838-1843.
  • [54]Adami HO, Malker B, Holmberg L, Persson I, Stone B: The relation between survival and age at diagnosis in breast cancer. N Engl J Med 1986, 315:559-563.
  • [55]Fredholm H, Eaker S, Frisell J, Holmberg L, Fredriksson I, Lindman H: Breast cancer in young women: poor survival despite intensive treatment. PLoS One 2009, 4:e7695.
  • [56]Bastiaannet E, Liefers GJ, de Craen AJ, Kuppen PJ, van de Water W, Portielje JE, van der Geest LG, Janssen-Heijnen ML, Dekkers OM, van de Velde CJ, Westendorp RG: Breast cancer in elderly compared to younger patients in the Netherlands: stage at diagnosis, treatment and survival in 127,805 unselected patients. Breast Cancer Res Treat 2010, 124:801-807.
  • [57]Chapman JA, Meng D, Shepherd L, Parulekar W, Ingle JN, Muss HB, Palmer M, Yu C, Goss PE: Competing causes of death from a randomized trial of extended adjuvant endocrine therapy for breast cancer. J Natl Cancer Inst 2008, 100:252-260.
  • [58]Schairer C, Mink PJ, Carroll L, Devesa SS: Probabilities of death from breast cancer and other causes among female breast cancer patients. J Natl Cancer Inst 2004, 96:1311-1321.
  • [59]Du XL, Fox EE, Lai D: Competing causes of death for women with breast cancer and change over time from 1975 to 2003. Am J Clin Oncol 2008, 31:105-116.
  • [60]Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S, Demeter J, Perou CM, Lønning PE, Brown PO, Børresen-Dale AL, Botstein D: Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A 2003, 100:8418-8423.
  • [61]Sotiriou C, Neo SY, McShane LM, Korn EL, Long PM, Jazaeri A, Martiat P, Fox SB, Harris AL, Liu ET: Breast cancer classification and prognosis based on gene expression profiles from a population-based study. Proc Natl Acad Sci U S A 2003, 100:10393-10398.
  • [62]Augoff K, McCue B, Plow EF, Sossey-Alaoui K: miR-31 and its host gene lncRNA LOC554202 are regulated by promoter hypermethylation in triple-negative breast cancer. Mol Cancer 2012, 11:5. BioMed Central Full Text
  • [63]Schwartz JC, Younger ST, Nguyen NB, Hardy DB, Monia BP, Corey DR, Janowski BA: Antisense transcripts are targets for activating small RNAs. Nat Struct Mol Biol 2008, 15:842-848.
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