LIU Xiyang, AN Yingying, YU Baoguo, QIN Guimin. Analysis of Commonly and Specifically Dysregulated Pathways in Three Women Cancers[J]. Chinese Journal of Electronics, 2018, 27(5): 1043-1049. doi: 10.1049/cje.2017.09.028
Citation: LIU Xiyang, AN Yingying, YU Baoguo, QIN Guimin. Analysis of Commonly and Specifically Dysregulated Pathways in Three Women Cancers[J]. Chinese Journal of Electronics, 2018, 27(5): 1043-1049. doi: 10.1049/cje.2017.09.028

Analysis of Commonly and Specifically Dysregulated Pathways in Three Women Cancers

doi: 10.1049/cje.2017.09.028
Funds:  This work is supported by the National Natural Science Foundation of China (No.61472311), National Defense Basic Research Project of China (No.jcky2016110c006), the Fundamental Research Funds for the Central Universities (No.BDZ011401), and the Natural Science Foundation of Shaanxi Province (No.2017JM6038).
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  • Corresponding author: QIN Guimin (corresponding author) was born in 1977. She currently is an associate professor at Xidian University. She has been conducting research for many years on complex networks, bioinformatics, and machine learning. (
  • Received Date: 2016-12-01
  • Rev Recd Date: 2017-05-01
  • Publish Date: 2018-09-10
  • Breast, ovarian and endometrial cancer are three most prevalent gynaecological malignancies. Identifying their common and specific biomarkers is significant for cancer prediction and therapy in females. We propose a method to identify dysregulated pathways in cancer through scoring pathways based on the molecular interaction data and genomic data. Commonly and specifically dysregulated pathways are analyzed across the above three female cancers, which have not been studied as a whole to the best of our knowledge. Our results demonstrate that all the three cancers have close relationships with Type Ⅱ diabetes and cell cycle-related biology processes. Breast cancer is specifically related to immune system while ovarian cancer and endometrial cancer are associated with blood vascular-related systems such as renin-angiotensin system and coagulation system. In addition, dysregulated pathways are used to predict potential driver genes effectively according to their topological structure and biological information.
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  • M. Al-Hajj, M.S. Wicha, A. Benito-Hernandez, et al., “Prospective identification of tumorigenic breast cancer cells”, Proc. Natl. Acad. Sci. USA, Vol.100, No.7, pp.3983-3988, 2003.
    The Cancer Genome Atlas Research Network, “Integrated genomic characterization of endometrial carcinoma”, Nature, Vol.497, No.7447, pp.67-73, 2013.
    The Cancer Genome Atlas Research Network, “Integrated genomic analysis of ovarian carcinoma”, Nature, Vol.474, No.27, pp.609-615, 2011.
    M.C. Pike, “Age-related factors in cancers of the breast, ovary, andendometrium”, J. Chronic Dis., Vol.40, No.87, pp.59S-69S, 1987.
    J.F. Ludvigsson, J. West, A. Ekbom, et al., “Reduced risk of breast, endometrial and ovarian cancer in women with celiac disease”, Int. J. Cancer, Vol.131, No.3, pp.E244-250, 2012.
    M. Grechkin, B.A. Logsdon, A.J. Gentles, et al., “Identifying network perturbation in cancer”, PLOS Comput. Biol., Vol.12, No.5, 2016.
    H. Yang, Q. Wei, X. Zhong, et al., “Cancer driver gene discovery through an integrative genomics approach in a non-parametric Bayesian framework”, Bioinformatics, Vol.33, No.4, pp.483-490, 2016.
    H.Y. Chuang, E. Lee, Y.T. Liu, et al., “Network-based classification of breast cancer metastasis”, Mol. Syst. Biol., Vol.3, No.1, pp.1440-1449, 2007.
    T.H. Hwang, G. Atluri, R. Kuang, et al., “Large-scale integrative network-based analysis identifies common pathways disrupted by copy number alterations across cancers”, BMC Genomics, Vol.14, No.1, pp.440-452, 2013.
    F. Vandin, E. Upfal and B.J. Raphael, “Algorithms for detecting significantly mutated pathways in cancer”, J. Comput. Biol., Vol.18, No.3, pp.507-522, 2011.
    W. Poole, K. Leinonen, I. Shmulevich, et al., “Multiscale mutation clustering algorithm identifies pan-cancer mutational clusters associated with pathway-level changes in gene expression”, PLOS Comput. Biol., Vol.13, No.2, DOI: 10.1371/journal.pcbi.1005347, 2017.
    D. Tanramluk, L. Narupiyakul, R. Akavipat, et al., “MANORAA (Mapping analogous nuclei onto residue and affinity) for identifying protein-ligand fragment interaction, pathways and SNPs”, Nucleic Acids Res., Vol.44, No.W1, pp.W514-W521, 2016.
    The Cancer Genome Atlas Research Network, “The cancer genome atlas pan—Cancer analysis project”, Nat. Genet., Vol.45, No.10, pp.1113-1120, 2013.
    K.A. Hoadley, C. Yau, D.M. Wolf, et al., “Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin”, Cell, Vol.158, No.4, pp.929-944, 2014.
    A. Liberzon, A. Subramanian, R. Pinchback, et al., “Molecular signatures database (MSigDB) 3.0”, Bioinformatics, Vol.27, No.12, pp.1739-1740, 2011.
    S. Peri, J.D. Navarro, R.Amanchy, et al., “Development of human protein reference database as an initial platform for approaching systems biology in humans”, Genome Res., Vol.13, No.10, pp.2363-2371, 2003.
    K.G. Becker, K.C. Barnes, T.J. Bright, et al., “The genetic association databas”, Nat. Genet., Vol.36, No.5, pp.431-432, 2004.
    P.A. Futreal, L. Coin, M. Marshall, et al., “A census of human cancer genes”, Nat. Rev. Cancer, Vol.4, No.3, pp.177-183, 2004.
    A. Hamosh, A.F. Scott, J.S. Amberger, et al., “Online mendelian inheritance in man (OMIM), a knowledgebase of human genes and genetic disorders”, Nucleic Acids Res., Vol.33, No.1, pp.D514-517, 2005.
    R.A. Fisher, “Statistical methods for research workers”, Int. J. Plant Sciences, Vol.96, No.3, pp.340-341, 1935.
    J.A. Royds, S.K. Dower, E.E. Qwarnstrom, et al., “Response of tumour cells to hypoxia: Role of p53 and NFkB”, Mol. Pathol., Vol.51, No.2, pp.55-61, 1998.
    A.L. Harris, “Hypoxia — a key regulatory factor in tumour growth”, Nat. Rev. Cancer, Vol.2, No.1, pp.38-47, 2002.
    C. Lagadec, S. Meignan and E. Adriaenssens, “TrkA overexpression enhances growth and metastasis of breast cancer cells”, Oncogene, Vol.28, No.18, pp.1960-1970, 2009.
    S.M. Albelda, “Role of integrins and other cell adhesion molecules in tumor progression and metastasis”, Lab Invest, Vol.68, No.1, pp.4-17, 1993.
    S.L. Bowker, S.R. Majumdar, P. Veugelers, et al., “Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin”, Diabetes Care, Vol.29, No.29, pp.254-258, 2006.
    M.R. Junttila and F.J. Sauvage, “Influence of tumourmicroenvironment heterogeneity on therapeutic response”, Nature, Vol.501, No.7467, pp.346-54, 2013.
    D.G. DeNardo, D.J. Brennan, E. Rexhepaj, et al., “Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy”, Cancer Discov., Vol.1, No.1, pp.54-67, 2011.
    D.G. DeNardo and L.M. Coussens, “Inflammation and breast cancer. Balancing immune response: crosstalk between adaptive and innate immune cells during breast cancer progression”, Breast Cancer Res., Vol.9, No.4, pp.212-221, 2007.
    N.S. Brown and R. Bicknell, “Hypoxia and oxidative stress in breast cancer. Oxidative stress: Its effects on the growth, metastatic potential and response to therapy of breast cancer”, Breast Cancer Res., Vol.3, No.5, pp.323-327, 2001.
    D. Hanahan and R.A. Weinberg, “The hallmarks of cancer”, Cell, Vol.100, No.1, pp.57-70, 2000.
    V. Zuco, V. Benedetti, M. De Cesare, et al., “Sensitization of ovarian carcinoma cells to the atypical retinoid ST1926 by the histone deacetylase inhibitor, RC307: Enhanced DNA damage response”, Int. J. Cancer, Vol.126, No.5, pp.1246-1255, 2010.
    J. Kang, A.D. D’Andrea and D. Kozono, “A DNA repair pathway-focused score for prediction of outcomes in ovarian cancer treated with platinum-based chemotherapy”, J. Natl. Cancer Inst., Vol.104, No.9, pp.670-681, 2012.
    A.S. Swierzko, K. Florczak, M. Cedzyński, et al., “Mannanbinding lectin (MBL) in women with tumours of the reproductive system”, Cancer Immunology Immunotherapy, Vol.56, No.7, pp.959-71, 2007.
    H. Pendeville, N. Carpino and J.C. Marine, “The ornithine decarboxylase gene is essential for cell survival during early murine development”, Mol Cell Biol., Vol.21, No.19. pp.6549-58, 2001.
    C.F. Holinka and E. Gurpide, “Ornithine decarboxylase activity in human endometrium and endometrial cancer cells”, In Vitro Cell. & Dev. Biology-Animal, Vol.21, No.12, pp.697-706, 1985.
    J. Adams, V.J. Palombella, E.A. Sausville, et al., “Proteasome inhibitors: A novel class of potent and effective antitumor agents”, Cancer Res., Vol.59, No.11, pp.2615-2622, 1999.
    E.E. Bosco, Y. Wang, H. Xu, et al., “The retinoblastoma tumor suppressor modifies the therapeutic response of breast cancer”, J. Clin. Invest., Vol.117, No.1, pp.218-228, 2007.
    Y. Dong, M.D. Walsh, M.A. McGuckin, et al., “Reduced expression of retinoblastoma gene product (pRB) and high expression of p53 are associated with poor prognosis in ovarian cancer”, Int. J. Cancer, Vol.74, No.4, pp.407-415, 1997.
    R.J. DeBerardinis, J.J. Lum, G. Hatzivassiliou, et al., “The biology of cancer: Metabolic reprogramming fuels cell growth and proliferation”, Cell Metab., Vol.7, No.1, pp.11-20, 2008.
    D.W. Cramer, “Lactase persistence and milk consumption as determinants of ovarian cancer risk”, Am. J. Epidemiol., Vol.130, No.5, pp.904-910, 1989.
    W.Y. Chen, E.R. Bertone-Johnson, D.J. Hunter, et al., “Associations between polymorphisms in the vitamin D receptor and breast cancer risk”, Cancer Epidemiol. Biomarkers & Prev., Vol.14, No.10, pp.2335-2339, 2005.
    H. Yabushita, M. Hirata, M. Noguchi, et al., “Vitamin D receptor in endometrial carcinoma and the differentiation-inducing effect of 1,25-dihydroxyvitamin D3 on endometrial carcinoma cell lines”, J. Obstet. and Gynaecol. Res., Vol.22, No.6, pp.529-539, 1996.
    Y. Zhang, Y. Xiong and W.G. Yarbrough, “ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways”, Cell, Vol.92, No.6, pp.725-734, 1998.
    K. Ino, K. Shibata, H. Kajiyama, et al., “Angiotensin Ⅱ type 1 receptor expression in ovarian cancer and its correlation with tumour angiogenesis and patient survival”, Br. J. Cancer, Vol.94, No.4, pp.552-560, 2006.
    A.W. Piastowska-Ciesielska, E. P luciennik, K. WójcikKrowiranda, et al., “Analysis of the expression of angiotensin Ⅱ type 1 receptor and VEGF in endometrial adenocarcinoma with different clinicopathological characteristics”, Tumour Biol., Vol.33, No.3, pp.767-774, 2012.
    G.F. Nash, D.C. Walsh and A.K. Kakkar, “The role of the coagulation system in tumour angiogenesis”, Lancet Oncol., Vol.2, No.10, pp.608-613, 2001.
    M. Cizkova, S. Vacher, D. Meseure, et al., “PIK3R1 underexpression is an independent prognostic marker in breast cancer”, BMC Cancer, Vol.13, N0.1, Page 545, 2013.
    B. Woynarowska, D.M. Skrincosky, A. Haag, et al., “Inhibition of lectin-mediated ovarian tumor cell adhesion by sugar analogs”, J. Biol. Chem., Vol.269, No.36, pp.22797-803, 1994
    P. Mehlen, S. Rabizadeh S.J. Snipas, et al., “The DCC gene product induces apoptosis by a mechanism requiring receptor proteolysis”, Nature, Vol.395, pp.801-804, 1998
    H. Kato, Y. Zhou, K. Asanoma, et al., “Suppressed tumorigenicity of human endometrial cancer cells by the restored expression of the DCC gene”, Br. J. Cancer, Vol.82, No.2, pp.459-466, 2000.
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