Abstract：In recent years, a growing number of epidemiological studies have shown that many kinds of cancer and Alzheimer′s disease have an inverse association, but the molecular biological mechanism remains unclear. Researching the inverse association from gene signal transduction and regulatory networks will play an important role in exploring the pathogenesis of both diseases. Breast cancer (BC) and AD were selected to be analyzed. Taking account of that the traditional genes extraction algorithms focused on a single gene expressed differently in different samples and ignored the links among the correlation genes, mutual information (MI) was utilized to extract the differentially expressed genes in the two diseases basing on the correlation among genes using as feature genes. In this paper, considering the limitation of network component analysis (NCA),such as the strong constraint conditions and the long running time, fast-network component analysis (FastNCA), improved by NCA,was brought up to get the activity of transcription factors among feature genes and TF′s regulate strength of target genes, and construct two diseases transcriptional regulatory networks, respectively. Experimental results showed that the activities and the regulate and control strength of TFs were totally opposite in the two diseases, for example POLR2E, RFC5, THOC4, FBXO22, KPNA1, MYST3 and PTBP1, for example, transcription factors RFC5 activities in BC decreased from 0.269 to 0.077, and in AD increased by -0.430 to 0.307. According to the experiment and analysis of molecular biology, the regulate relationship and the biological process influence from these TFs play a vital role in BC and AD.
刘芳, 孔薇, 牟晓阳. 基于互信息研究的乳腺癌与阿尔茨海默症的免疫系统发病机理探寻[J]. 中国生物医学工程学报, 2016, 35(3): 292-300.
Liu Fang, Kong Wei, Mou Xiaoyang. Exploration of Pathogenesis in Immune System of Breast Cancer and Alzheimer′s Disease Based on Mutual Information. Chinese Journal of Biomedical Engineering, 2016, 35(3): 292-300.
[1] Catalá-López F, Crespo-Facorro B, Vieta E, et al. Alzheimer′s disease and cancer: current epidemiological evidence for a mutual protection[J]. Neuroepidemiology, 2014, 42(2): 121-122. [2] Driver JA. Inverse association between cancer and neurodegenerative disease: review of the epidemiologic and biological evidence[J]. Biogerontology, 2014, 15(6): 547-557. [3] Realmuto S, Cinturino A, Arnao V, et al. Tumor diagnosis preceding Alzheimer’s disease onset: is there a link between cancer and Alzheimer’s disease?[J]. Journal of Alzheimer's Disease, 2012, 31(1): 177-182. [4] 张焕萍,王惠南,卢光明,等. 基于互信息的差异共表达致病基因挖掘方法[J]. 东南大学学报: 自然科学版, 2009, 39(1): 151-155. [5] Chang C, Ding Z, Hung YS, et al. Fast network component analysis for gene regulation networks[C]// 2007 IEEE Workshop on Machine Learning for Signal Processing. Thessaloniki:IEEE, 2007: 21-26. [6] Chang C, Ding Z, Hung YS, et al. Fast network component analysis (FastNCA) for gene regulatory network reconstruction from microarray data[J]. Bioinformatics, 2008, 24(11): 1349-1358. [7] 孙啸,陆祖宏,谢建明. 生物信息学基础[M]. 北京:清华大学出版社,2005. [8] Liao JC, Boscolo R, Yang YL, et al. Network component analysis: reconstruction of regulatory signals in biological systems[J]. Proceedings of the National Academy of Sciences, 2003, 100(26): 15522-15527. [9] Steuer R, Kurths J, Daub CO, et al. The mutual information: detecting and evaluating dependencies between variables[J]. Bioinformatics, 2002, 18(Suppl 2): S231-S240. [10] Gene Ontology Consortium. The Gene Ontology (GO) database and informatics resource[J]. Nucleic Acids Research, 2004, 32(Suppl 1): D258-D261. [11] Kanehisa M, Goto S. KEGG: Kyoto encyclopedia of genes and genomes[J]. Nucleic Acids Research, 2000, 28(1): 27-30. [12] Demetrius LA, Simon DK. The inverse association of cancer and Alzheimer's: A bioenergetic mechanism[J]. Journal of the Royal Society Interface, 2013, 10(82): 20130006. [13] Ye X, Xiao P, Hu X, et al. Crystallization and preliminary X-ray analysis of the RPB5 subunit of human RNA polymerase II[J]. Acta Crystallographica Section F: Structural Biology and Crystallization Communications, 2011, 67(11): 1391-1393. [14] Reisman D, Glaros S, Thompson EA. The SWI/SNF complex and cancer[J]. Oncogene, 2009, 28(14): 1653-1668. [15] Schirer Y, Malishkevich A, Ophir Y, et al. Novel marker for the onset of frontotemporal dementia: early increase in activity-dependent neuroprotective protein (ADNP) in the face of Tau mutation[J]. PloS ONE, 2014, 9(1): e87383. [16] Zhang W, Walker E, Tamplin OJ, et al. Zfp206 regulates ES cell gene expression and differentiation[J]. Nucleic Acids Research, 2006, 34(17): 4780-4790. [17] Pilar AVC, Reid-Yu SA, Cooper CA, et al. Active modification of host inflammation by Salmonella[J]. Gut microbes, 2013, 4(2): 140-145. [18] Kim NH, Yoshimaru T, Chen YA, et al. BIG3 inhibits the estrogen-dependent nuclear translocation of PHB2 via multiple karyopherin-alpha proteins in breast cancer Cells[J]. PLoS ONE, 2015, 10(6):e0127707. [19] Sheikh BN, Phipson B, El-Saafin F, et al. MOZ (MYST3, KAT6A) inhibits senescence via the INK4A-ARF pathway[J]. Oncogene, 2015,34(47): 5807-5820. [20] He X, Arslan AD, Ho TT, et al. Involvement of polypyrimidine tract-binding protein (PTBP1) in maintaining breast cancer cell growth and malignant properties[J]. Oncogenesis, 2014, 3(1): e84.
