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Inferring Dysregulated Pathways of Driving Cancer Subtypes Through Multi-omics Integration

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Bioinformatics Research and Applications (ISBRA 2018)

Part of the book series: Lecture Notes in Computer Science ((LNBI,volume 10847))

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Abstract

The rapid accumulation of multi-omics cancer data has created the opportunity for biological discovery and biomedical applications. In this study, we propose an approach that integrates multi-omics data to identify dysregulated pathways driving cancer subtypes, which simultaneously considers DNA methylation, DNA copy number, somatic mutation and gene expression profiles. After applying it to Breast Invasive Carcinoma (BRCA) in TCGA, we identify distinct top 30 dysregulated pathways for each breast cancer subtypes. The result suggests that dysregulated pathways of different subtypes display common and specific patterns. Furthermore, 44 differentially expressed genes with corresponding genetic and epigenetic dysregulation are retrieved from the subtype-specific pathways. Literature validation and functional enrichment analysis indicate that these genes are function associated with BRCA. Our method provides a new insight for identifying the driver of cancer subtypes through multi-omics data integration.

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References

  1. Adams, J.R., Schachter, N.F., Liu, J.C., et al.: Elevated PI3K signaling drives multiple breast cancer subtypes. Oncotarget 2(6), 435–447 (2011)

    Article  Google Scholar 

  2. Andre, F., Job, B., Dessen, P., et al.: Molecular characterization of breast cancer with high-resolution oligonucleotide comparative genomic hybridization array. Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res. 15(2), 441–451 (2009)

    Article  Google Scholar 

  3. Balko, J.M., Schwarz, L.J., Bhola, N.E., et al.: Activation of MAPK pathways due to DUSP4 loss promotes cancer stem cell-like phenotypes in basal-like breast cancer. Cancer Res. 73(20), 6346–6358 (2013)

    Article  Google Scholar 

  4. Bergamaschi, A., Kim, Y.H., Wang, P., et al.: Distinct patterns of dna copy number alteration are associated with different clinicopathological features and gene-expression subtypes of breast cancer. Genes. Chromosom. Cancer 45(11), 1033–1040 (2006)

    Article  Google Scholar 

  5. Cancer Genome Atlas Network: Comprehensive molecular portraits of human breast tumours. Nature 490(7418), 61–70 (2012)

    Article  Google Scholar 

  6. Cheng, F., Zhao, J., Zhao, Z.: Advances in computational approaches for prioritizing driver mutations and significantly mutated genes in cancer genomes. Brief. Bioinform. 17(4), 642–656 (2015)

    Article  Google Scholar 

  7. Creixell, P., Reimand, J., Haider, S., et al.: Pathway and network analysis of cancer genomes. Nat. Methods 12(7), 615 (2015)

    Article  Google Scholar 

  8. Dimitrakopoulos, C.M., Beerenwinkel, N.: Computational approaches for the identification of cancer genes and pathways. Wiley Interdiscip. Rev. Syst. Biol. Med. 9(1) (2017)

    Google Scholar 

  9. Dutta, B., Pusztai, L., Qi, Y., et al.: A network-based, integrative study to identify core biological pathways that drive breast cancer clinical subtypes. Br. J. Cancer 106(6), 1107–1116 (2012)

    Article  Google Scholar 

  10. Eckert, L.B., Repasky, G.A., Ulkü, A.S., et al.: Involvement of ras activation in human breast cancer cell signaling, invasion, and anoikis. Cancer Res. 64(13), 4585–4592 (2004)

    Article  Google Scholar 

  11. Fruman, D.A., Chiu, H., Hopkins, B.D., Bagrodia, S., et al.: The PI3K pathway in human disease. Cell 170(4), 605–635 (2017)

    Article  Google Scholar 

  12. Futreal, P.A., Coin, L., Marshall, M., et al.: A census of human cancer genes. Nat. Rev. Cancer 4(3), 177–183 (2004)

    Article  Google Scholar 

  13. Glaser, S.L., Ambinder, R.F., DiGiuseppe, J.A., et al.: Absence of Epstein-Barr virus EBER-1 transcripts in an epidemiologically diverse group of breast cancers. Int. J. Cancer 75(4), 555–558 (1998)

    Article  Google Scholar 

  14. Han, L., Maciejewski, M., Brockel, C., et al.: A probabilistic pathway score (PROPS) for classification with applications to inflammatory bowel disease. Bioinformatics 1, 9 (2017)

    Google Scholar 

  15. Hollander, M.C., Blumenthal, G.M., Dennis, P.A.: PTEN loss in the continuum of common cancers, rare syndromes and mouse models. Nat. Rev. Cancer 11(4), 289–301 (2011)

    Article  Google Scholar 

  16. Hung, J.H., Whitfield, T.W., Yang, T.H., et al.: Identification of functional modules that correlate with phenotypic difference: the influence of network topology. Genome Biol. 11(2), 1 (2010)

    Article  Google Scholar 

  17. Isakoff, S.J., Engelman, J.A., Irie, H.Y., et al.: Breast cancer-associated PIK3CA mutations are oncogenic in mammary epithelial cells. Cancer Res. 65(23), 10992–11000 (2005)

    Article  Google Scholar 

  18. Jhaveri, T.Z., Woo, J., Shang, X., et al.: AMP-activated kinase (AMPK) regulates activity of HER2 and EGFR in breast cancer. Oncotarget 6(17), 14754–14765 (2015)

    Article  Google Scholar 

  19. Khabaz, M.N.: Association of Epstein-Barr virus infection and breast carcinoma. Arch. Med. Sci. 9(4), 745–751 (2013)

    Article  Google Scholar 

  20. Lee, E., Chuang, H.Y., Kim, J.W., et al.: Inferring pathway activity toward precise disease classification. PLoS Comput. Biol. 4(11), e1000217 (2008)

    Article  Google Scholar 

  21. Li, D.M., Feng, Y.M.: Signaling mechanism of cell adhesion molecules in breast cancer metastasis: potential therapeutic targets. Breast Cancer Res. Treat. 128(1), 7–21 (2011)

    Article  Google Scholar 

  22. Liu, W., Bai, X., Liu, Y., et al.: Topologically inferring pathway activity toward precise cancer classification via integrating genomic and metabolomic data: prostate cancer as a case. Sci. Rep. 5, 13192 (2015)

    Article  Google Scholar 

  23. Logue, J.S., Morrison, D.K.: Complexity in the signaling network: insights from the use of targeted inhibitors in cancer therapy. Genes Dev. 26(7), 641–650 (2012)

    Article  Google Scholar 

  24. Magrath, I., Bhatia, K.: Breast cancer: a new Epstein-Barr virus-associated disease? J. Natl. Cancer Inst. 91(16), 1349–1350 (1999)

    Article  Google Scholar 

  25. Marcotte, R., Sayad, A., Brown, K.R., et al.: Functional genomic landscape of human breast cancer drivers, vulnerabilities, and resistance. Cell 164(1–2), 293–309 (2016)

    Article  Google Scholar 

  26. McLaughlin, S.K., Olsen, S.N., et al.: The RasGAP gene, RASAL2, is a tumor and metastasis suppressor. Cancer Cell 24(3), 365–378 (2013)

    Article  Google Scholar 

  27. Mosesson, Y., Mills, G.B., Yarden, Y.: Derailed endocytosis: an emerging feature of cancer. Nat. Rev. Cancer 8(11), 835–850 (2008)

    Article  Google Scholar 

  28. Ouadid-Ahidouch, H., Dhennin-Duthille, I., Gautier, M., et al.: TRP calcium channel and breast cancer: expression, role and correlation with clinical parameters. Bull. Cancer 99(6), 655–664 (2012)

    Article  Google Scholar 

  29. Peng, H., Long, F., Ding, C.: Feature selection based on mutual information criteria of max-dependency, max-relevance, and min-redundancy. IEEE Trans. Pattern Anal. Mach. Intell. 27(8), 1226–1238 (2005)

    Article  Google Scholar 

  30. Troxell, M.L., Levine, J., Beadling, C., et al.: High prevalence of PIK3CA/AKT pathway mutations in papillary neoplasms of the breast. Mod. Pathol. Off. J. U.S. Can. Acad. Pathol. Inc. 23(1), 27–37 (2010)

    Google Scholar 

  31. Ulitsky, I., Shamir, R.: Pathway redundancy and protein essentiality revealed in the Saccharomyces cerevisiae interaction networks. Mol. Syst. Biol. 3, 104 (2007)

    Article  Google Scholar 

  32. Zhang, J., Zhang, S.: Discovery of cancer common and specific driver gene sets. Nucleic Acids Res. 45(10), e86 (2017)

    Article  Google Scholar 

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Acknowledgements

This work was supported by the National NSFC (Grant No. 61532014 & No. 61432010 & No. 61672407 & No. 61772395), the Fundamental Research Funds for the Central Universities (No. JB150303) and the Fundamental Research Funds for young teacher (2017KY0264).

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Correspondence to Lin Gao .

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Shi, K., Gao, L., Wang, B. (2018). Inferring Dysregulated Pathways of Driving Cancer Subtypes Through Multi-omics Integration. In: Zhang, F., Cai, Z., Skums, P., Zhang, S. (eds) Bioinformatics Research and Applications. ISBRA 2018. Lecture Notes in Computer Science(), vol 10847. Springer, Cham. https://doi.org/10.1007/978-3-319-94968-0_9

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  • DOI: https://doi.org/10.1007/978-3-319-94968-0_9

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-94967-3

  • Online ISBN: 978-3-319-94968-0

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