Integration of Clinico-Pathological and microRNA Data for Intelligent Breast Cancer Relapse Prediction Systems
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Abstract
This paper investigates the integration of clinico-pathological and microRNA data for breast cancer relapse prediction. Clinical and pathological data proved to be relevant in making predictions about cancer disease outcome. The most accurate predictive models can be obtained by using clinico-pathological information together with genomic information. We analyzed the performance of various combinations between twenty classification algorithms and thirteen feature selection methods. The best performer was the regularized regression method Elastic Net, using its built-in feature selection method, on the data set integrating clinico-pathological data with microRNAs. The hybrid signature contains four clinico-pathological features and fifteen microRNAs. We also evaluated the influence of the separation of patients according to ER status and the impact of the exclusion from the data set of HS molecules (novel microRNAs without an assigned miRBase ID) on the overall performance. Functional analysis of the microRNAs of the best classifier showed that they are involved in cancer related processes.
Keywords
microRNA Clinico-pathological data Breast cancer relapse Predictive models RegularizationReferences
- 1.Metacore gene expression and pathway analysis. http://www.genego.com/metacore.php
- 2.Antonov, A.V., Knight, R.A., Melino, G., Barlev, N.A., Tsvetkov, P.O.: Mirumir: an online tool to test micrornas as biomarkers to predict survival in cancer using multiple clinical data sets. Cell Death Differ. 20(2), 367 (2013). http://dx.doi.org/10.1038/cdd.2012.137L3
- 3.Bergamaschi, A., Katzenellenbogen, B.S.: Tamoxifen downregulation of mir-451 increases 14-3-3zeta and promotes breast cancer cell survival and endocrine resistance. Oncogene 31(1), 39–47 (2012)CrossRefGoogle Scholar
- 4.Breiman, L.: Random forests. Mach. Learn. 45(1), 5–32 (2001)CrossRefzbMATHGoogle Scholar
- 5.Buelmann, P., Yu, B.: Boosting with the l2 loss: regression and classification. J. Am. Stat. Assoc. 98, 324–339 (2003)CrossRefGoogle Scholar
- 6.Buffa, F.M., Camps, C., Winchester, L., Snell, C.E., Gee, H.E., Sheldon, H., Taylor, M., Harris, A.L., Ragoussis, J.: Microrna-associated progression pathways and potential therapeutic targets identified by integrated mrna and microrna expression profiling in breast cancer. Cancer Res. 71(17), 5635–5645 (2011)CrossRefGoogle Scholar
- 7.Burns, L.J., Weisdorf, D.J., et al.: Il-2-based immunotherapy after autologous transplantation for lymphoma and breast cancer induces immune activation and cytokine release: a phase i/ii trial. Bone Marrow Transplant. 32(2), 177–186 (2003)CrossRefGoogle Scholar
- 8.Calin, G.A., Croce, C.M.: MicroRNA signatures in human cancers. Nat. Rev. Cancer 6(11), 857–866 (2006)CrossRefGoogle Scholar
- 9.Castellano, L., Giamas, G., et al.: The estrogen receptor-alpha-induced microrna signature regulates itself and its transcriptional response. Proc. Natl. Acad. Sci. USA 106(37), 15732–15737 (2009)CrossRefGoogle Scholar
- 10.Chen, J., Bardes, E., Aronow, B., Jegga, A.: Toppgene suite for gene list enrichment analysis and candidate gene prioritization. Nucleic Acids Res. 37(suppl 2), W305–W311 (2009)CrossRefGoogle Scholar
- 11.Duda, R., Hart, P., Stork, D.: Pattern Classification. Wiley-Interscience, New-York (2001)zbMATHGoogle Scholar
- 12.Edén, P., Ritz, C., Rose, C., Fernö, M., Peterson, C.: “Good old” clinical markers have similar power in breast cancer prognosis as microarray gene expression profilers. Eur. J. Cancer 40, 1837–1841 (2004)CrossRefGoogle Scholar
- 13.Edgar, R., Domrachev, M., Lash, A.E.: Gene expression omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 30(1), 207–210 (2002)CrossRefGoogle Scholar
- 14.Eifel, P., Axelson, J.A., Costa, J., Crowley, J., Curran, W.J., Deshler, A., Fulton, S., Hendricks, C.B., Kemeny, M., Kornblith, A.B., Louis, T.A., Markman, M., Mayer, R., Roter, D.: National institutes of health consensus development conference statement: adjuvant therapy for breast cancer, November 1–3, 2000. J. natl. cancer inst. 93(13), 979–989 (2001)CrossRefGoogle Scholar
- 15.Famili, F., Phan, S., Fauteux, F., Liu, Z., Pan, Y.: Data integration and knowledge discovery in life sciences. In: García-Pedrajas, N., Herrera, F., Fyfe, C., Benítez, J.M., Ali, M. (eds.) IEA/AIE 2010, Part III. LNCS (LNAI), vol. 6098, pp. 102–111. Springer, Heidelberg (2010) CrossRefGoogle Scholar
- 16.Floares, A., Birlutiu, A.: Decision tree models for developing molecular classifiers for cancer diagnosis. In: The 2012 International Joint Conference on Neural Networks (IJCNN), pp. 1–7. IEEE (2012)Google Scholar
- 17.Fontana, L., Pelosi, E. et al.: MicroRNAs 17–5p-20a-106a control monocytopoiesis through AML1 targeting and M-CSF receptor upregulation. Nat. Cell Biol. 9(7), 775–787 (2007). http://dx.doi.org/10.1038/ncb1613
- 18.Friedman, J., Trevor, H., Tibshirani, R.: Regularization paths for generalized linear models via coordinate descent. J. Stat. Softw. 33(1), 1–22 (2010). http://www.jstatsoft.org/v33/i01/
- 19.Gaffen, S.L., Liu, K.D.: Overview of interleukin-2 function, production and clinical applications. Cytokine 28(3), 109–123 (2004). http://www.sciencedirect.com/science/article/pii/S1043466604002200
- 20.Gevaert, O., Smet, F.D., Timmerman, D., Moreau, Y., Moor, B.D.: Predicting the prognosis of breast cancer by integrating clinical and microarray data with bayesian networks. Bioinformatics 22(14), e184–e190 (2006)CrossRefGoogle Scholar
- 21.Goldhirsch, A., Wood, W.C., Gelber, R.D., Coates, A.S., Thürlimann, B., Senn, H.J.: Meeting highlights: updated international expert consensus on the primary therapy of early breast cancer. J. Clin. Oncol. 21(17), 3357–3365 (2003)CrossRefGoogle Scholar
- 22.González, S., Guerra, L., Robles, V., Peña, J., Famili, F.: Clidapa: a new approach to combining clinical data with dna microarrays. Intell. Data Anal. 14(2), 207–223 (2010)Google Scholar
- 23.Guo, L., Zhao, Y., Yang, S., Cai, M., Wu, Q., Chen, F.: Genome-wide screen for aberrantly expressed mirnas reveals mirna profile signature in breast cancer. Mol. Biol. Rep. 40(3), 2175–2186 (2013)CrossRefGoogle Scholar
- 24.Han, Y., Chen, J., et al.: MicroRNA expression signatures of bladder cancer revealed by deep sequencing. PLoS ONE 6(3), 6 (2011)Google Scholar
- 25.Hanahan, D., Weinberg, R.: Hallmarks of cancer: the next generation. Cell 144(5), 646–674 (2011)CrossRefGoogle Scholar
- 26.He, Y., Cui, Y., et al.: Hypomethylation of the hsa-mir-191 locus causes high expression of hsa-miR-191 and promotes the epithelial-to-mesenchymal transition in hepatocellular carcinoma. Neoplasia 13(9), 841–853 (2011)Google Scholar
- 27.da Huang, W., Sherman, B., Lempicki, R.: Systematic and integrative analysis of large gene lists using david bioinformatics resources. Nature Protoc. 1, 44–57 (2008)CrossRefGoogle Scholar
- 28.Ioannidis, J.P.: Microarrays and molecular research: noise discovery? Lancet 365(9458), 454–455 (2005)CrossRefGoogle Scholar
- 29.Kozomara, A., Griffiths-Jones, S.: miRBase: integrating microRNAannotation and deep-sequencing data. Nucleic Acids Res. 39(Database-Issue), 152–157 (2011). http://dblp.uni-trier.de/db/journals/nar/nar39.html#KozomaraG11d
- 30.Li, Q.Q., Chen, Z.Q., et al.: Involvement of NF-kappaB/miR-448 regulatory feedback loop in chemotherapy-induced epithelial-mesenchymal transition of breast cancer cells. Cell Death Differ. 18(1), 16–25 (2011)CrossRefGoogle Scholar
- 31.Ma, J., Jemal, A.: Breast cancer statistics. In: Ahmad, A. (ed.) Breast Cancer Metastasis and Drug Resistance, pp. 1–18. Springer, New York (2013)CrossRefGoogle Scholar
- 32.Massague, J.: TGFbeta in cancer. Cell 134(2), 215–230 (2008)CrossRefGoogle Scholar
- 33.Mosakhani, N., Guled, M., et al.: An integrated analysis of miRNA and gene copy numbers in xenografts of Ewing’s sarcoma. J. Exp. Clin. Cancer Res. 31, 24 (2012)CrossRefGoogle Scholar
- 34.R Development Core Team: R: A language and environment for statistical computing. R Foundation for Statistical Computing 1(2.11.1), 409 (2011). http://www.r-project.org
- 35.Rocha, R.L., Hilsenbeck, S.G., et al.: Insulin-like growth factor binding protein-3 and insulin receptor substrate-1 in breast cancer: correlation with clinical parameters and disease-free survival. Clin. Cancer Res. 3(1), 103–109 (1997)Google Scholar
- 36.Schoeffner, D.J., Matheny, S.L., et al.: VEGF contributes to mammary tumor growth in transgenic mice through paracrine and autocrine mechanisms. Lab Invest. 85(5), 608–623 (2005)CrossRefGoogle Scholar
- 37.Schölkopf, B., Smola, A.J.: Learning with Kernels: Support Vector Machines, Regularization, Optimization, and Beyond. MIT Press, Cambridge (2002). http://www.learning-with-kernels.org
- 38.Slawski, M., Boulesteix, A.L., Bernau., C.: CMA: Synthesis of microarray-based classification, r package version 1.16.0. (2009)Google Scholar
- 39.Sun, Y., Goodison, S., Li, J., Liu, L., Farmerie, W.: Improved breast cancer prognosis through the combination of clinical and genetic markers. Bioinformatics 23(1), 30–37 (2007)CrossRefGoogle Scholar
- 40.Turner, B.C., Haffty, B.G., et al.: Insulin-like growth factor-I receptor overexpression mediates cellular radioresistance and local breast cancer recurrence after lumpectomy and radiation. Cancer Res. 57(15), 3079–3083 (1997)Google Scholar
- 41.van’t Veer, L.J., Dai, H., Van De Vijver, M.J., He, Y.D., Hart, A.A., Mao, M., Peterse, H.L., van der Kooy, K., Marton, M.J., Witteveen, A.T., et al.: Gene expression profiling predicts clinical outcome of breast cancer. Nature 415(6871), 530–536 (2002)Google Scholar
- 42.van Vliet, M.H., Horlings, H.M., van de Vijver, M.J., Reinders, M.J., Wessels, L.F.: Integration of clinical and gene expression data has a synergetic effect on predicting breast cancer outcome. PLoS ONE 7(7), e40358 (2012)CrossRefGoogle Scholar
- 43.Volinia, S., Calin, G.A., et al.: A microRNA expression signature of human solid tumors defines cancer gene targets. Proc. Natl. Acad. Sci. USA 103(7), 2257–2261 (2006)CrossRefGoogle Scholar
- 44.Wang, F., Zheng, Z., Guo, J., Ding, X.: Correlation and quantitation of microRNA aberrant expression in tissues and sera from patients with breast tumor. Gynecol. Oncol. 119(3), 586–593 (2010)CrossRefGoogle Scholar
- 45.Wong, J.: Package ‘imputation’, version 2.0.1. https://github.com/jeffwong/imputation
- 46.Xiao-Hua, Z., Obuchowski, N., McClish, D.: Statistical methods in diagnostic medicine (2002)Google Scholar
- 47.Yi, H., Liang, B., et al.: Differential roles of miR-199a-5p in radiation-induced autophagy in breast cancer cells. FEBS Lett. 587(5), 436–443 (2013)CrossRefMathSciNetGoogle Scholar
- 48.Zhu, H., Wu, H., Liu, X., Evans, B.R., Medina, D.J., Liu, C.G., Yang, J.M.: Role of microRNA miR-27a and miR-451 in the regulation of MDR1/P-glycoprotein expression in human cancer cells. Biochem. Pharmacol. 76(5), 582–588 (2008)CrossRefGoogle Scholar
- 49.Zhu, J., Hastie, T.: Classification of gene microarrays by penalized logistic regression. Biostatistics 5(3), 427–443 (2004)CrossRefzbMATHGoogle Scholar
- 50.Zou, H., Hastie, T.: Regularization and variable selection via the elastic net. J. Roy. Stat. Soc.: Ser. B (Stat. Methodol.) 67(2), 301–320 (2005)CrossRefzbMATHMathSciNetGoogle Scholar