{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T08:15:49Z","timestamp":1768464949491,"version":"3.49.0"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Cancer"],"published-print":{"date-parts":[[2009,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Mammalian target of rapamycin (mTOR) is a serine\/threonine kinase involved in multiple intracellular signaling pathways promoting tumor growth. mTOR is aberrantly activated in a significant portion of breast cancers and is a promising target for treatment. Rapamycin and its analogues are in clinical trials for breast cancer treatment. Patterns of gene expression (metagenes) may also be used to simulate a biologic process or effects of a drug treatment. In this study, we tested the hypothesis that the gene-expression signature regulated by rapamycin could predict disease outcome for patients with breast cancer.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Colony formation and sulforhodamine B (IC<jats:sub>50<\/jats:sub> &lt; 1 nM) assays, and xenograft animals showed that MDA-MB-468 cells were sensitive to treatment with rapamycin. The comparison of <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> gene expression data identified a signature, termed rapamycin metagene index (RMI), of 31 genes upregulated by rapamycin treatment <jats:italic>in vitro<\/jats:italic> as well as <jats:italic>in vivo<\/jats:italic> (false discovery rate of 10%). In the Miller dataset, RMI did not correlate with tumor size or lymph node status. High (&gt;75th percentile) RMI was significantly associated with longer survival (<jats:italic>P<\/jats:italic> = 0.015). On multivariate analysis, RMI (<jats:italic>P<\/jats:italic> = 0.029), tumor size (<jats:italic>P<\/jats:italic> = 0.015) and lymph node status (<jats:italic>P<\/jats:italic> = 0.001) were prognostic. In van 't Veer study, RMI was not associated with the time to develop distant metastasis (<jats:italic>P<\/jats:italic> = 0.41). In the Wang dataset, RMI predicted time to disease relapse (<jats:italic>P<\/jats:italic> = 0.009).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Rapamycin-regulated gene expression signature predicts clinical outcome in breast cancer. This supports the central role of mTOR signaling in breast cancer biology and provides further impetus to pursue mTOR-targeted therapies for breast cancer treatment.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1476-4598-8-75","type":"journal-article","created":{"date-parts":[[2009,9,29]],"date-time":"2009-09-29T10:23:20Z","timestamp":1254219800000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["The rapamycin-regulated gene expression signature determines prognosis for breast cancer"],"prefix":"10.1186","volume":"8","author":[{"given":"Argun","family":"Akcakanat","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Spiridon","family":"Tsavachidis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Funda","family":"Meric-Bernstam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2009,9,24]]},"reference":[{"key":"460_CR1","volume-title":"J Clin Oncol","author":"F Meric-Bernstam","year":"2009","unstructured":"Meric-Bernstam F, Gonzalez-Angulo AM: Targeting the mTOR Signaling Network for Cancer Therapy. J Clin Oncol. 2009."},{"key":"460_CR2","doi-asserted-by":"publisher","first-page":"772","DOI":"10.4161\/cbt.3.8.994","volume":"3","author":"KE Bachman","year":"2004","unstructured":"Bachman KE, Argani P, Samuels Y, Silliman N, Ptak J, Szabo S, Konishi H, Karakas B, Blair BG, Lin C: The PIK3CA gene is mutated with high frequency in human breast cancers. Cancer Biol Ther. 2004, 3: 772-775.","journal-title":"Cancer Biol Ther"},{"key":"460_CR3","doi-asserted-by":"publisher","first-page":"2554","DOI":"10.1158\/0008-5472-CAN-04-3913","volume":"65","author":"LH Saal","year":"2005","unstructured":"Saal LH, Holm K, Maurer M, Memeo L, Su T, Wang X, Yu JS, Malmstrom PO, Mansukhani M, Enoksson J: PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma. Cancer Res. 2005, 65: 2554-2559. 10.1158\/0008-5472-CAN-04-3913","journal-title":"Cancer Res"},{"key":"460_CR4","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1126\/science.3798106","volume":"235","author":"DJ Slamon","year":"1987","unstructured":"Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL: Human breast cancer: correlation of relapse and survival with amplification of the HER-2\/neu oncogene. Science. 1987, 235: 177-182. 10.1126\/science.3798106","journal-title":"Science"},{"key":"460_CR5","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1007\/BF01809293","volume":"16","author":"M Bolla","year":"1990","unstructured":"Bolla M, Chedin M, Souvignet C, Marron J, Arnould C, Chambaz E: Estimation of epidermal growth factor receptor in 177 breast cancers: correlation with prognostic factors. Breast Cancer Res Treat. 1990, 16: 97-102. 10.1007\/BF01809293","journal-title":"Breast Cancer Res Treat"},{"key":"460_CR6","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1210\/me.2002-0318","volume":"17","author":"X Cui","year":"2003","unstructured":"Cui X, Zhang P, Deng W, Oesterreich S, Lu Y, Mills GB, Lee AV: Insulin-like growth factor-I inhibits progesterone receptor expression in breast cancer cells via the phosphatidylinositol 3-kinase\/Akt\/mammalian target of rapamycin pathway: progesterone receptor as a potential indicator of growth factor activity in breast cancer. Mol Endocrinol. 2003, 17: 575-588. 10.1210\/me.2002-0318","journal-title":"Mol Endocrinol"},{"key":"460_CR7","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1083\/jcb.200112015","volume":"158","author":"J Chung","year":"2002","unstructured":"Chung J, Bachelder RE, Lipscomb EA, Shaw LM, Mercurio AM: Integrin (alpha 6 beta 4) regulation of eIF-4E activity and VEGF translation: a survival mechanism for carcinoma cells. J Cell Biol. 2002, 158: 165-174. 10.1083\/jcb.200112015","journal-title":"J Cell Biol"},{"key":"460_CR8","first-page":"3657","volume":"57","author":"E Rhei","year":"1997","unstructured":"Rhei E, Kang L, Bogomolniy F, Federici MG, Borgen PI, Boyd J: Mutation analysis of the putative tumor suppressor gene PTEN\/MMAC1 in primary breast carcinomas. Cancer Res. 1997, 57: 3657-3659.","journal-title":"Cancer Res"},{"key":"460_CR9","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1159\/000086981","volume":"68","author":"S Tsutsui","year":"2005","unstructured":"Tsutsui S, Inoue H, Yasuda K, Suzuki K, Higashi H, Era S, Mori M: Reduced expression of PTEN protein and its prognostic implications in invasive ductal carcinoma of the breast. Oncology. 2005, 68: 398-404. 10.1159\/000086981","journal-title":"Oncology"},{"key":"460_CR10","doi-asserted-by":"publisher","first-page":"6084","DOI":"10.1158\/0008-5472.CAN-07-6854","volume":"68","author":"K Stemke-Hale","year":"2008","unstructured":"Stemke-Hale K, Gonzalez-Angulo AM, Lluch A, Neve RM, Kuo WL, Davies M, Carey M, Hu Z, Guan Y, Sahin A: An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer. Cancer Res. 2008, 68: 6084-6091. 10.1158\/0008-5472.CAN-07-6854","journal-title":"Cancer Res"},{"key":"460_CR11","doi-asserted-by":"publisher","first-page":"R37","DOI":"10.1186\/bcr569","volume":"5","author":"O Stal","year":"2003","unstructured":"Stal O, Perez-Tenorio G, Akerberg L, Olsson B, Nordenskjold B, Skoog L, Rutqvist LE: Akt kinases in breast cancer and the results of adjuvant therapy. Breast Cancer Res. 2003, 5: R37-44. 10.1186\/bcr569","journal-title":"Breast Cancer Res"},{"key":"460_CR12","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1002\/ijc.2910640412","volume":"64","author":"A Bellacosa","year":"1995","unstructured":"Bellacosa A, de Feo D, Godwin AK, Bell DW, Cheng JQ, Altomare DA, Wan M, Dubeau L, Scambia G, Masciullo V: Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas. Int J Cancer. 1995, 64: 280-285. 10.1002\/ijc.2910640412","journal-title":"Int J Cancer"},{"key":"460_CR13","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1038\/modpathol.3800525","volume":"19","author":"S Bose","year":"2006","unstructured":"Bose S, Chandran S, Mirocha JM, Bose N: The Akt pathway in human breast cancer: a tissue-array-based analysis. Mod Pathol. 2006, 19: 238-245. 10.1038\/modpathol.3800525","journal-title":"Mod Pathol"},{"key":"460_CR14","doi-asserted-by":"publisher","first-page":"721","DOI":"10.7164\/antibiotics.28.721","volume":"28","author":"C Vezina","year":"1975","unstructured":"Vezina C, Kudelski A, Sehgal SN: Rapamycin (AY-22, 989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle. J Antibiot (Tokyo). 1975, 28: 721-726.","journal-title":"J Antibiot (Tokyo)"},{"key":"460_CR15","doi-asserted-by":"publisher","first-page":"6680","DOI":"10.1038\/sj.onc.1204091","volume":"19","author":"M Hidalgo","year":"2000","unstructured":"Hidalgo M, Rowinsky EK: The rapamycin-sensitive signal transduction pathway as a target for cancer therapy. Oncogene. 2000, 19: 6680-6686. 10.1038\/sj.onc.1204091","journal-title":"Oncogene"},{"key":"460_CR16","doi-asserted-by":"publisher","first-page":"5314","DOI":"10.1200\/JCO.2005.66.130","volume":"23","author":"S Chan","year":"2005","unstructured":"Chan S, Scheulen ME, Johnston S, Mross K, Cardoso F, Dittrich C, Eiermann W, Hess D, Morant R, Semiglazov V: Phase II study of temsirolimus (CCI-779), a novel inhibitor of mTOR, in heavily pretreated patients with locally advanced or metastatic breast cancer. J Clin Oncol. 2005, 23: 5314-5322. 10.1200\/JCO.2005.66.130","journal-title":"J Clin Oncol"},{"key":"460_CR17","doi-asserted-by":"publisher","first-page":"14863","DOI":"10.1073\/pnas.95.25.14863","volume":"95","author":"MB Eisen","year":"1998","unstructured":"Eisen MB, Spellman PT, Brown PO, Botstein D: Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci USA. 1998, 95: 14863-14868. 10.1073\/pnas.95.25.14863","journal-title":"Proc Natl Acad Sci USA"},{"key":"460_CR18","doi-asserted-by":"publisher","first-page":"4648","DOI":"10.1038\/sj.onc.1210245","volume":"26","author":"CJ Creighton","year":"2007","unstructured":"Creighton CJ: A gene transcription signature of the Akt\/mTOR pathway in clinical breast tumors. Oncogene. 2007, 26: 4648-4655. 10.1038\/sj.onc.1210245","journal-title":"Oncogene"},{"key":"460_CR19","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/S0092-8674(03)00570-1","volume":"114","author":"J Lamb","year":"2003","unstructured":"Lamb J, Ramaswamy S, Ford HL, Contreras B, Martinez RV, Kittrell FS, Zahnow CA, Patterson N, Golub TR, Ewen ME: A mechanism of cyclin D1 action encoded in the patterns of gene expression in human cancer. Cell. 2003, 114: 323-334. 10.1016\/S0092-8674(03)00570-1","journal-title":"Cell"},{"key":"460_CR20","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/ng1490","volume":"37","author":"A Sweet-Cordero","year":"2005","unstructured":"Sweet-Cordero A, Mukherjee S, Subramanian A, You H, Roix JJ, Ladd-Acosta C, Mesirov J, Golub TR, Jacks T: An oncogenic KRAS2 expression signature identified by cross-species gene-expression analysis. Nat Genet. 2005, 37: 48-55.","journal-title":"Nat Genet"},{"key":"460_CR21","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1038\/nature04296","volume":"439","author":"AH Bild","year":"2006","unstructured":"Bild AH, Yao G, Chang JT, Wang Q, Potti A, Chasse D, Joshi MB, Harpole D, Lancaster JM, Berchuck A: Oncogenic pathway signatures in human cancers as a guide to targeted therapies. Nature. 2006, 439: 353-357. 10.1038\/nature04296","journal-title":"Nature"},{"key":"460_CR22","doi-asserted-by":"publisher","first-page":"3903","DOI":"10.1158\/0008-5472.CAN-05-4363","volume":"66","author":"CJ Creighton","year":"2006","unstructured":"Creighton CJ, Hilger AM, Murthy S, Rae JM, Chinnaiyan AM, El-Ashry D: Activation of mitogen-activated protein kinase in estrogen receptor alpha-positive breast cancer cells in vitro induces an in vivo molecular phenotype of estrogen receptor alpha-negative human breast tumors. Cancer Res. 2006, 66: 3903-3911. 10.1158\/0008-5472.CAN-05-4363","journal-title":"Cancer Res"},{"key":"460_CR23","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1158\/1078-0432.CCR-03-0043","volume":"10","author":"WC Noh","year":"2004","unstructured":"Noh WC, Mondesire WH, Peng J, Jian W, Zhang H, Dong J, Mills GB, Hung MC, Meric-Bernstam F: Determinants of rapamycin sensitivity in breast cancer cells. Clin Cancer Res. 2004, 10: 1013-1023. 10.1158\/1078-0432.CCR-03-0043","journal-title":"Clin Cancer Res"},{"key":"460_CR24","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1677\/erc.0.0080249","volume":"8","author":"K Yu","year":"2001","unstructured":"Yu K, Toral-Barza L, Discafani C, Zhang WG, Skotnicki J, Frost P, Gibbons JJ: mTOR, a novel target in breast cancer: the effect of CCI-779, an mTOR inhibitor, in preclinical models of breast cancer. Endocr Relat Cancer. 2001, 8: 249-258. 10.1677\/erc.0.0080249","journal-title":"Endocr Relat Cancer"},{"key":"460_CR25","doi-asserted-by":"publisher","first-page":"7031","DOI":"10.1158\/1078-0432.CCR-04-0361","volume":"10","author":"WH Mondesire","year":"2004","unstructured":"Mondesire WH, Jian W, Zhang H, Ensor J, Hung MC, Mills GB, Meric-Bernstam F: Targeting mammalian target of rapamycin synergistically enhances chemotherapy-induced cytotoxicity in breast cancer cells. Clin Cancer Res. 2004, 10: 7031-7042. 10.1158\/1078-0432.CCR-04-0361","journal-title":"Clin Cancer Res"},{"key":"460_CR26","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","volume":"102","author":"A Subramanian","year":"2005","unstructured":"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 USA. 2005, 102: 15545-15550. 10.1073\/pnas.0506580102","journal-title":"Proc Natl Acad Sci USA"},{"key":"460_CR27","doi-asserted-by":"publisher","first-page":"13550","DOI":"10.1073\/pnas.0506230102","volume":"102","author":"LD Miller","year":"2005","unstructured":"Miller LD, Smeds J, George J, Vega VB, Vergara L, Ploner A, Pawitan Y, Hall P, Klaar S, Liu ET, Bergh J: An expression signature for p53 status in human breast cancer predicts mutation status, transcriptional effects, and patient survival. Proc Natl Acad Sci USA. 2005, 102: 13550-13555. 10.1073\/pnas.0506230102","journal-title":"Proc Natl Acad Sci USA"},{"key":"460_CR28","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1016\/S0140-6736(05)70933-8","volume":"365","author":"Y Wang","year":"2005","unstructured":"Wang Y, Klijn JG, Zhang Y, Sieuwerts AM, Look MP, Yang F, Talantov D, Timmermans M, Meijer-van Gelder ME, Yu J: Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet. 2005, 365: 671-679.","journal-title":"Lancet"},{"key":"460_CR29","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1038\/415530a","volume":"415","author":"LJ van't Veer","year":"2002","unstructured":"van't Veer LJ, Dai H, Vijver van de MJ, He YD, Hart AA, Mao M, Peterse HL, Kooy van der K, Marton MJ, Witteveen AT: Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002, 415: 530-536. 10.1038\/415530a","journal-title":"Nature"},{"key":"460_CR30","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1038\/ng1180","volume":"34","author":"VK Mootha","year":"2003","unstructured":"Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, Puigserver P, Carlsson E, Ridderstrale M, Laurila E: PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet. 2003, 34: 267-273. 10.1038\/ng1180","journal-title":"Nat Genet"},{"key":"460_CR31","doi-asserted-by":"publisher","first-page":"2737","DOI":"10.1074\/jbc.M309999200","volume":"279","author":"JF Gera","year":"2004","unstructured":"Gera JF, Mellinghoff IK, Shi Y, Rettig MB, Tran C, Hsu JH, Sawyers CL, Lichtenstein AK: AKT activity determines sensitivity to mammalian target of rapamycin (mTOR) inhibitors by regulating cyclin D1 and c-myc expression. J Biol Chem. 2004, 279: 2737-2746. 10.1074\/jbc.M309999200","journal-title":"J Biol Chem"},{"key":"460_CR32","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1038\/nm1052","volume":"10","author":"PK Majumder","year":"2004","unstructured":"Majumder PK, Febbo PG, Bikoff R, Berger R, Xue Q, McMahon LM, Manola J, Brugarolas J, McDonnell TJ, Golub TR: mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways. Nat Med. 2004, 10: 594-601. 10.1038\/nm1052","journal-title":"Nat Med"},{"key":"460_CR33","doi-asserted-by":"publisher","first-page":"7564","DOI":"10.1073\/pnas.0702507104","volume":"104","author":"LH Saal","year":"2007","unstructured":"Saal LH, Johansson P, Holm K, Gruvberger-Saal SK, She QB, Maurer M, Koujak S, Ferrando AA, Malmstrom P, Memeo L: Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity. Proc Natl Acad Sci USA. 2007, 104: 7564-7569. 10.1073\/pnas.0702507104","journal-title":"Proc Natl Acad Sci USA"},{"key":"460_CR34","doi-asserted-by":"publisher","first-page":"6779","DOI":"10.1158\/1078-0432.CCR-04-0112","volume":"10","author":"X Zhou","year":"2004","unstructured":"Zhou X, Tan M, Stone Hawthorne V, Klos KS, Lan KH, Yang Y, Yang W, Smith TL, Shi D, Yu D: Activation of the Akt\/mammalian target of rapamycin\/4E-BP1 pathway by ErbB2 overexpression predicts tumor progression in breast cancers. Clin Cancer Res. 2004, 10: 6779-6788. 10.1158\/1078-0432.CCR-04-0112","journal-title":"Clin Cancer Res"},{"key":"460_CR35","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1089\/omi.2006.10.429","volume":"10","author":"F Bertucci","year":"2006","unstructured":"Bertucci F, Finetti P, Cervera N, Maraninchi D, Viens P, Birnbaum D: Gene expression profiling and clinical outcome in breast cancer. Omics. 2006, 10: 429-443. 10.1089\/omi.2006.10.429","journal-title":"Omics"},{"key":"460_CR36","doi-asserted-by":"publisher","first-page":"2069","DOI":"10.1517\/14656566.7.15.2069","volume":"7","author":"O Modlich","year":"2006","unstructured":"Modlich O, Prisack HB, Bojar H: Breast cancer expression profiling: the impact of microarray testing on clinical decision making. Expert Opin Pharmacother. 2006, 7: 2069-2078. 10.1517\/14656566.7.15.2069","journal-title":"Expert Opin Pharmacother"},{"key":"460_CR37","volume-title":"Breast Cancer Res Treat","author":"CJ Creighton","year":"2008","unstructured":"Creighton CJ, Kent Osborne C, Vijver van de MJ, Foekens JA, Klijn JG, Horlings HM, Nuyten D, Wang Y, Zhang Y, Chamness GC: Molecular profiles of progesterone receptor loss in human breast tumors. Breast Cancer Res Treat. 2008."},{"key":"460_CR38","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1016\/j.ccr.2006.10.008","volume":"10","author":"RM Neve","year":"2006","unstructured":"Neve RM, Chin K, Fridlyand J, Yeh J, Baehner FL, Fevr T, Clark L, Bayani N, Coppe JP, Tong F: A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell. 2006, 10: 515-527. 10.1016\/j.ccr.2006.10.008","journal-title":"Cancer Cell"},{"key":"460_CR39","doi-asserted-by":"publisher","first-page":"10869","DOI":"10.1073\/pnas.191367098","volume":"98","author":"T Sorlie","year":"2001","unstructured":"Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, Rijn van de M, Jeffrey SS: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001, 98: 10869-10874. 10.1073\/pnas.191367098","journal-title":"Proc Natl Acad Sci USA"},{"key":"460_CR40","doi-asserted-by":"publisher","first-page":"8418","DOI":"10.1073\/pnas.0932692100","volume":"100","author":"T Sorlie","year":"2003","unstructured":"Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S: Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA. 2003, 100: 8418-8423. 10.1073\/pnas.0932692100","journal-title":"Proc Natl Acad Sci USA"},{"key":"460_CR41","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1158\/1078-0432.CCR-07-0999","volume":"14","author":"BK Tan","year":"2008","unstructured":"Tan BK, Tan LK, Yu K, Tan PH, Lee M, Sii LH, Wong CY, Ho GH, Yeo AW, Chow PK: Clinical validation of a customized multiple signature microarray for breast cancer. Clin Cancer Res. 2008, 14: 461-469. 10.1158\/1078-0432.CCR-07-0999","journal-title":"Clin Cancer Res"},{"key":"460_CR42","doi-asserted-by":"publisher","first-page":"1999","DOI":"10.1056\/NEJMoa021967","volume":"347","author":"MJ van de Vijver","year":"2002","unstructured":"van de Vijver MJ, He YD, van't Veer LJ, Dai H, Hart AA, Voskuil DW, Schreiber GJ, Peterse JL, Roberts C, Marton MJ: A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002, 347: 1999-2009. 10.1056\/NEJMoa021967","journal-title":"N Engl J Med"},{"key":"460_CR43","doi-asserted-by":"publisher","first-page":"3207","DOI":"10.1158\/1078-0432.CCR-06-2765","volume":"13","author":"C Desmedt","year":"2007","unstructured":"Desmedt C, Piette F, Loi S, Wang Y, Lallemand F, Haibe-Kains B, Viale G, Delorenzi M, Zhang Y, d'Assignies MS: Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the TRANSBIG multicenter independent validation series. Clin Cancer Res. 2007, 13: 3207-3214. 10.1158\/1078-0432.CCR-06-2765","journal-title":"Clin Cancer Res"},{"key":"460_CR44","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/S0140-6736(03)14023-8","volume":"362","author":"JC Chang","year":"2003","unstructured":"Chang JC, Wooten EC, Tsimelzon A, Hilsenbeck SG, Gutierrez MC, Elledge R, Mohsin S, Osborne CK, Chamness GC, Allred DC, O'Connell P: Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer. Lancet. 2003, 362: 362-369. 10.1016\/S0140-6736(03)14023-8","journal-title":"Lancet"},{"key":"460_CR45","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1016\/j.ccr.2004.05.015","volume":"5","author":"XJ Ma","year":"2004","unstructured":"Ma XJ, Wang Z, Ryan PD, Isakoff SJ, Barmettler A, Fuller A, Muir B, Mohapatra G, Salunga R, Tuggle JT: A two-gene expression ratio predicts clinical outcome in breast cancer patients treated with tamoxifen. Cancer Cell. 2004, 5: 607-616. 10.1016\/j.ccr.2004.05.015","journal-title":"Cancer Cell"},{"key":"460_CR46","doi-asserted-by":"publisher","first-page":"2284","DOI":"10.1200\/JCO.2004.05.166","volume":"22","author":"M Ayers","year":"2004","unstructured":"Ayers M, Symmans WF, Stec J, Damokosh AI, Clark E, Hess K, Lecocke M, Metivier J, Booser D, Ibrahim N: Gene expression profiles predict complete pathologic response to neoadjuvant paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide chemotherapy in breast cancer. J Clin Oncol. 2004, 22: 2284-2293. 10.1200\/JCO.2004.05.166","journal-title":"J Clin Oncol"},{"key":"460_CR47","doi-asserted-by":"publisher","first-page":"1961","DOI":"10.1158\/0008-5472.CAN-04-2501","volume":"65","author":"J Dong","year":"2005","unstructured":"Dong J, Peng J, Zhang H, Mondesire WH, Jian W, Mills GB, Hung MC, Meric-Bernstam F: Role of glycogen synthase kinase 3beta in rapamycin-mediated cell cycle regulation and chemosensitivity. Cancer Res. 2005, 65: 1961-1972. 10.1158\/0008-5472.CAN-04-2501","journal-title":"Cancer Res"},{"key":"460_CR48","doi-asserted-by":"publisher","first-page":"14424","DOI":"10.1074\/jbc.273.23.14424","volume":"273","author":"S Hashemolhosseini","year":"1998","unstructured":"Hashemolhosseini S, Nagamine Y, Morley SJ, Desrivieres S, Mercep L, Ferrari S: Rapamycin inhibition of the G1 to S transition is mediated by effects on cyclin D1 mRNA and protein stability. J Biol Chem. 1998, 273: 14424-14429. 10.1074\/jbc.273.23.14424","journal-title":"J Biol Chem"},{"key":"460_CR49","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1038\/nbt836","volume":"21","author":"L Zhang","year":"2003","unstructured":"Zhang L, Miles MF, Aldape KD: A model of molecular interactions on short oligonucleotide microarrays. Nat Biotechnol. 2003, 21: 818-821. 10.1038\/nbt836","journal-title":"Nat Biotechnol"},{"key":"460_CR50","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1093\/bioinformatics\/btg148","volume":"19","author":"S Pounds","year":"2003","unstructured":"Pounds S, Morris SW: Estimating the occurrence of false positives and false negatives in microarray studies by approximating and partitioning the empirical distribution of p-values. Bioinformatics. 2003, 19: 1236-1242. 10.1093\/bioinformatics\/btg148","journal-title":"Bioinformatics"}],"container-title":["Molecular Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1476-4598-8-75.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T23:31:05Z","timestamp":1630452665000},"score":1,"resource":{"primary":{"URL":"https:\/\/molecular-cancer.biomedcentral.com\/articles\/10.1186\/1476-4598-8-75"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,9,24]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2009,12]]}},"alternative-id":["460"],"URL":"https:\/\/doi.org\/10.1186\/1476-4598-8-75","relation":{},"ISSN":["1476-4598"],"issn-type":[{"value":"1476-4598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,9,24]]},"assertion":[{"value":"8 April 2009","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 September 2009","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 September 2009","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"75"}}