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Investigating the Common Molecular Pathways and Key Biomarkers Associated with Late-Onset Alzheimer’s Disease and Hepatocellular Carcinoma by Bioinformatic Analysis

Yıl 2020, Cilt: 46 Sayı: 2, 161 - 168, 01.08.2020
https://doi.org/10.32708/uutfd.738750

Öz

Recent studies suggest a potential link between Alzheimer's disease (AD) and cancer yet lack of evidence exists to understand the shared mechanism underlying both diseases. Accumulating research investigating the association between AD and specific types of cancers such as breast, lung and prostate cancer claim inverse relationship between them however possible molecular relationship between AD and hepatocellular carcinoma (HCC) has not been well studied. In this study, we reanalyzed RNA-sequencing data sets related to late-onset AD (LOAD) and HCC to identify common differentially expressed genes (DEGs), molecular pathways as well as key miRNA regulators that may involve in the pathogenesis of both diseases. The data sets were retrieved from NCBI-GEO omnibus database and analyzed by GREIN web tool. Overlapped DEGs were identified and their functional enrichments were analyzed by NetworkAnalyst. Cytoscape software was used to visualize network and identify hub genes. MicroRNAs targeting the hub genes were also determined by mirDIP database. A total of 33 DEGs were found to be dysregulated in both datasets and five genes (HLA-A, HLA-C, TRIM31, HLA-DQB2, HLA-DRB1) were identified as hub genes that possibly involve in the shared molecular etiology of both diseases. Our analyses revealed that common DEGs are enriched in molecular pathways related immune system and multiple miRNA regulators are likely to coregulate the expressions of shared hub genes. The results emphasize in silico evidence of common molecular background for LOAD and HCC, which can be ultimately utilized for risk assessments and drug development approaches for both diseases.

Kaynakça

  • 1. Uddin MS, Ashraf GM. Introductory Chapter: Alzheimer’s Disease-The Most Common Cause of Dementia. Advances in Dementia Research, London: IntechOpen; 2019. 1-8.
  • 2. Bekris LM, Yu CE, Bird TD, et al. Genetics of Alzheimer disease. J Geriatr Psychiatry Neurol 2010;23(4):213-27.
  • 3. Goldman JS, Hahn SE, Catania JW, et al. American College of Medical Genetics and the National Society of Genetic Counselors. Genetic counseling and testing for Alzheimer disease: joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors. Genet Med 2011;13(6):597-605.
  • 4. Kunkle BW, Grenier-Boley B, Sims R, et al. Alzheimer Disease Genetics Consortium (ADGC),; European Alzheimer’s Disease Initiative (EADI), Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE), Genetic and Environmental Risk in AD/Defining Genetic, Polygenic and Environmental Risk for Alzheimer’s Disease Consortium (GERAD/PERADES), Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing. Nat Genet 2019;51(3):414-430.
  • 5. Ozaki K, Niida S. Genetic Background for Alzheimer's Disease: Knowledge Accumulated from AD GWAS. Brain Nerve 2019;71(10):1039-1051.
  • 6. 2019 Alzheimer’s Disease Facts and Figures. Alzheimers Dement 2019;15(3):32)
  • 7. Toledo JB, Arnold M, Kastenmüller G, et al. Alzheimer's Disease Neuroimaging Initiative and the Alzheimer Disease Metabolomics Consortium. Metabolic network failures in Alzheimer's disease: A biochemical road map. Alzheimers Dement 2017;13(9):965-984.
  • 8. Clarke JR, Ribeiro FC, Frozza RL, et al. Metabolic Dysfunction in Alzheimer's Disease: From Basic Neurobiology to Clinical Approaches. J Alzheimers Dis 2018;64(s1):S405-S426.
  • 9. Kapogiannis D, Mattson MP. Disrupted energy metabolism and neuronal circuit dysfunction in cognitive impairment and Alzheimer's disease. Lancet Neurol 2011;10(2):187-98.
  • 10. Craft S. The role of metabolic disorders in Alzheimer disease and vascular dementia: two roads converged. Arch Neurol 2009;66(3):300-5. 11. Majd S, Power J, Majd Z. Alzheimer's Disease and Cancer: When Two Monsters Cannot Be Together. Front Neurosci 2019;13:155.
  • 12. Frain L, Swanson D, Cho K, et al. Association of cancer and Alzheimer's disease risk in a national cohort of veterans. Alzheimers Dement 2017;13(12):1364-1370.
  • 13. Musicco M, Adorni F, Di Santo S, et al. Inverse occurrence of cancer and Alzheimer disease: a population-based incidence study. Neurology 2013 23;81(4):322-8.
  • 14. Driver JA, Beiser A, Au R, et al. Inverse association between cancer and Alzheimer's disease: results from the Framingham Heart Study. BMJ 2012;344:e1442.
  • 15. Catalá-López F, Suárez-Pinilla M, Suárez-Pinilla P, et al. Inverse and direct cancer comorbidity in people with central nervous system disorders: a meta-analysis of cancer incidence in 577,013 participants of 50 observational studies. Psychother Psychosom 2014;83(2):89-105.
  • 16. Roe CM, Behrens MI, Xiong C, et al. Alzheimer disease and cancer. Neurology 2005;64(5):895-8.
  • 17. Roe CM, Fitzpatrick AL, Xiong C, et al. Cancer linked to Alzheimer disease but not vascular dementia. Neurology 2010;74(2):106-12.
  • 18. Ou SM, Lee YJ, Hu YW, et al. Does Alzheimer's disease protect against cancers? A nationwide population based study. Neuroepidemiology 2013;40(1):42-9.
  • 19. Lee JE, Kim D, Lee JH. Association between Alzheimer's Disease and Cancer Risk in South Korea: an 11-year Nationwide Population-Based Study. Dement Neurocogn Disord 2018;17(4):137-147.
  • 20. Zhang Q, Guo S, Zhang X, et al. Inverse relationship between cancer and Alzheimer's disease: a systemic review meta-analysis. Neurol Sci 2015;36(11):1987-94.
  • 21. Shafi O. Inverse relationship between Alzheimer's disease and cancer, and other factors contributing to Alzheimer's disease: a systematic review. BMC Neurol 2016;16(1):236.
  • 22. Nudelman KNH, McDonald BC, Lahiri DK, Saykin AJ. Biological Hallmarks of Cancer in Alzheimer's Disease. Mol Neurobiol 2019;56(10):7173-7187.
  • 23. Behrens MI, Lendon C, Roe CM. A common biological mechanism in cancer and Alzheimer's disease? Curr Alzheimer Res 2009;6(3):196-204.
  • 24. Lehrer S. Glioma and Alzheimer's Disease. J Alzheimers Dis Rep 2018;2(1):213-218.
  • 25. Lehrer S, Rheinstein PH. Alzheimer's Disease Susceptibility Genes in Malignant Breast Tumors. Cancer Transl Med 2019;5(2):42-46.
  • 26. Holohan KN, Lahiri DK, Schneider BP, Foroud T, Saykin AJ. Functional microRNAs in Alzheimer's disease and cancer: differential regulation of common mechanisms and pathways. Front Genet 2013;3:323.
  • 27. Nagaraj S, Zoltowska KM, Laskowska-Kaszub K, Wojda U. microRNA diagnostic panel for Alzheimer's disease and epigenetic trade-off between neurodegeneration and cancer. Ageing Res Rev 2019;49:125-143.
  • 28. Monacelli F, Cea M, Borghi R, Odetti P, Nencioni A. Do Cancer Drugs Counteract Neurodegeneration? Repurposing for Alzheimer's Disease. J Alzheimers Dis 2017;55(4):1295–1306. 29. Vargas DM, De Bastiani MA, Zimmer ER, Klamt F. Alzheimer's disease master regulators analysis: search for potential molecular targets and drug repositioning candidates. Alzheimers Res Ther 2018;10(1):59.
  • 30. Clough E, Barrett T. The Gene Expression Omnibus Database. Methods Mol Biol 2016;1418:93-110.
  • 31. Mahi NA, Najafabadi MF, Pilarczyk M, Kouril M, Medvedovic M. GREIN: An Interactive Web Platform for Re-analyzing GEO RNA-seq Data. Sci Rep 2019;9(1):7580.
  • 32. Szklarczyk D, Gable AL, Lyon D, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res 2019;47(D1):D607-D613.
  • 33. Chin CH, Chen SH, Wu HH, Ho CW, Ko MT, Lin CY. cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst Biol 2014;8 Suppl 4:S11.
  • 34. Ideker T, Sharan R. Protein networks in disease. Genome Res 2008;18(4):644-52. 35. Xia J, Gill EE, Hancock RE. NetworkAnalyst for statistical, visual and network-based meta-analysis of gene expression data. Nat Protoc 2015;10(6):823-44.
  • 36. Tokar T, Pastrello C, Rossos AEM, et al. mirDIP 4.1-integrative database of human microRNA target predictions. Nucleic Acids Res 2018;46(D1):D360-D370.
  • 37. Seddighi S, Houck AL, Rowe JB, Pharoah PDP. Evidence of a Causal Association Between Cancer and Alzheimer's Disease: a Mendelian Randomization Analysis. Sci Rep 2019;9(1):13548.
  • 38. Ibáñez K, Boullosa C, Tabarés-Seisdedos R, Baudot A, Valencia A. Molecular evidence for the inverse comorbidity between central nervous system disorders and cancers detected by transcriptomic meta-analyses. PLoS Genet 2014;10(2):e1004173.
  • 39. Lehrer S, Rheinstein PH. Alzheimer's Disease Susceptibility Genes in Malignant Breast Tumors. Cancer Transl Med 2019;5(2):42-46.
  • 40. Sánchez-Valle J, Tejero H, Ibáñez K, et al. A molecular hypothesis to explain direct and inverse co-morbidities between Alzheimer’s Disease, Glioblastoma and Lung cancer Sci Rep 2017;7(1):4474.
  • 41. Battaglia C, Venturin M, Sojic A, et al. Candidate Genes and MiRNAs Linked to the Inverse Relationship Between Cancer and Alzheimer's Disease: Insights From Data Mining and Enrichment Analysis. Front Genet 2019;10:846.
  • 42. Tunissiolli NM, Castanhole-Nunes MMU, Biselli-Chicote PM, et al. Hepatocellular Carcinoma: a Comprehensive Review of Biomarkers, Clinical Aspects, and Therapy. Asian Pac J Cancer Prev 2017;18(4):863-872.
  • 43. Kinney JW, Bemiller SM, Murtishaw AS, Leisgang AM, Salazar AM, Lamb BT. Inflammation as a central mechanism in Alzheimer's disease. Alzheimers Dement (N Y) 2018;4:575–590.
  • 44. Newcombe EA, Camats-Perna J, Silva ML, Valmas N, Huat TJ, Medeiros R. Inflammation: the link between comorbidities, genetics, and Alzheimer's disease. J Neuroinflammation 2018;15(1):276.
  • 45. Heppner FL, Ransohoff RM, Becher B. Immune attack: the role of inflammation in Alzheimer disease. Nat Rev Neurosci 2015;16(6):358-372.
  • 46. Keenan BP, Fong L, Kelley RK. Immunotherapy in hepatocellular carcinoma: the complex interface between inflammation, fibrosis, and the immune response. J Immunother Cancer 2019;7(1):267.
  • 47. Bishayee A. The role of inflammation and liver cancer. Adv Exp Med Biol 2014;816:401-435.
  • 48. Yu LX, Ling Y, Wang HY. Role of nonresolving inflammation in hepatocellular carcinoma development and progression. NPJ Precis Oncol 2018;2(1):6.
  • 49. Garrido C, Paco L, Romero I, et al. MHC class I molecules act as tumor suppressor genes regulating the cell cycle gene expression, invasion and intrinsic tumorigenicity of melanoma cells. Carcinogenesis 2012;33(3):687-693.
  • 50. Garrido F. MHC/HLA Class I Loss in Cancer Cells. Adv Exp Med Biol 2019;1151:15-78.
  • 51. Axelrod ML, Cook RS, Johnson DB, Balko JM. Biological Consequences of MHC-II Expression by Tumor Cells in Cancer. Clin Cancer Res 2019;25(8):2392-2402
  • 52. Ciccocioppo F, Lanuti P, Pierdomenico L, et al. The Characterization of Regulatory T-Cell Profiles in Alzheimer's Disease and Multiple Sclerosis. Sci Rep 2019;9(1):8788.
  • 53. Chitnis T, Weiner HL. CNS inflammation and neurodegeneration. J Clin Invest 2017;127(10):3577-3587.
  • 54. Nataf S. Autoimmunity as a Driving Force of Cognitive Evolution. Front Neurosci 2017;11:582.
  • 55. Baruch K, Rosenzweig N, Kertser A, et al. Breaking immune tolerance by targeting Foxp3(+) regulatory T cells mitigates Alzheimer's disease pathology. Nat Commun 2015;6:7967.
  • 56. Guo P, Ma X, Zhao W, et al. TRIM31 is upregulated in hepatocellular carcinoma and promotes disease progression by inducing ubiquitination of TSC1-TSC2 complex. Oncogene 2018;37(4):478-488.
  • 57. Yang Y, Wang H, Kouadir M, Song H, Shi F. Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors. Cell Death Dis 2019;10(2):128.
  • 58. Yin J, Zhao F, Chojnacki JE, et al. NLRP3 Inflammasome Inhibitor Ameliorates Amyloid Pathology in a Mouse Model of Alzheimer's Disease. Mol Neurobiol 2018;55(3):1977-1987.
  • 59. Danborg PB, Simonsen AH, Waldemar G, Heegaard NH. The potential of microRNAs as biofluid markers of neurodegenerative diseases-a systematic review. Biomarkers 2014;19(4):259-268.
  • 60. Van Giau V, An SS. Emergence of exosomal miRNAs as a diagnostic biomarker for Alzheimer's disease. J Neurol Sci 2016;360:141-152.
  • 61. Tan W, Liu B, Qu S, Liang G, Luo W, Gong C. MicroRNAs and cancer: Key paradigms in molecular therapy. Oncol Lett 2018;15(3):2735-2742.
  • 62. Zhang ZQ, Meng H, Wang N, et al. Serum microRNA 143 and microRNA 215 as potential biomarkers for the diagnosis of chronic hepatitis and hepatocellular carcinoma. Diagn Pathol 2014;9:135.
  • 63. Dong H, Li J, Huang L, et al. Serum MicroRNA Profiles Serve as Novel Biomarkers for the Diagnosis of Alzheimer's Disease. Dis Markers 2015;2015:625659.
  • 64. Cheng L, Doecke JD, Sharples RA, et al. Australian Imaging, Biomarkers and Lifestyle (AIBL) Research Group. Prognostic serum miRNA biomarkers associated with Alzheimer's disease shows concordance with neuropsychological and neuroimaging assessment. Mol Psychiatry 2015;20(10):1188-1196.

Geç Başlangıçlı Alzheimer Hastalığı ve Hepatosellüler Karsinom ile İlişkili Ortak Moleküler Yolakların ve Anahtar Biyobelirteçlerin Biyoinformatik Analizlerle Araştırılması

Yıl 2020, Cilt: 46 Sayı: 2, 161 - 168, 01.08.2020
https://doi.org/10.32708/uutfd.738750

Öz

Son zamanlardaki çalışmalarda Alzheimer hastalığı (AH) ve kanser arasında bir bağlantı olduğu ortaya konmuş fakat ortak mekanizmayı açıklayacak yeterince kanıt mevcut değildir. Bu bağlantıyı araştıran birçok çalışmada özellikle meme, prostat ve akciğer gibi kanser türleri ile AH arasında ters ilişki olduğu gösterilmekle beraber hepatosellüler karsinom (HCC) ve AH arasındaki ilişki henüz aydınlatılmamıştır. Bu çalışmada, geç başlangıçlı AH (LOAD) ve HCC ile ilişkili RNA dizileme (RNA-seq) verilerini biyoinformatik araçlarla analiz ederek iki hastalığın patogenezinde etkin olması muhtemel ortak moleküler yolakları, ortak diferansiyel olarak ifade olan genleri (DEG) ve aday anahtar miRNA’ları tespit etmeyi amaçladık. RNA-seq veri setleri NCBI-GEO omnibus veri tabanından alınarak GREIN web uygulaması ile analiz edildi. Ortak DEG’ler tespit edilerek, fonksiyon zenginleştirme analizleri NetworkAnalyst ile yapıldı. Network görselleştirme ve hub gen tespiti Cytoscape programı ile gerçekleştirildi. Hub genleri hedef alan miRNA’lar mirDIP veri tabanı ile belirlendi. Analiz sonucunda iki veri setinde ortak disregüle olan 33 DEG tespit edildi ve network analizinde iki hastalığın moleküler etiyolojisinde olası rolü olan ortak 5 hub gen (HLA-A, HLA-C, TRIM31, HLA-DQB2, HLA-DRB) belirlendi. Ortak DEG'lerin immun sistemle ilişkili moleküler yolaklarda ve biyolojik süreçlerde etkin olduğunu gözlemlendi. Ortak hub genlerin koregülasyonunda potansiyel düzenleyici rolleri olabilecek iki hastalıkla da ilişkili olduğu tahmin edilen birçok miRNA bulundu. Sonuçlarımız, her iki hastalık için risk değerlendirmesi ve ilaç geliştirme yaklaşımları için kullanılabilecek ortak moleküler mekanizmayı in silico kanıtlarla vurgulamaktadır.

Kaynakça

  • 1. Uddin MS, Ashraf GM. Introductory Chapter: Alzheimer’s Disease-The Most Common Cause of Dementia. Advances in Dementia Research, London: IntechOpen; 2019. 1-8.
  • 2. Bekris LM, Yu CE, Bird TD, et al. Genetics of Alzheimer disease. J Geriatr Psychiatry Neurol 2010;23(4):213-27.
  • 3. Goldman JS, Hahn SE, Catania JW, et al. American College of Medical Genetics and the National Society of Genetic Counselors. Genetic counseling and testing for Alzheimer disease: joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors. Genet Med 2011;13(6):597-605.
  • 4. Kunkle BW, Grenier-Boley B, Sims R, et al. Alzheimer Disease Genetics Consortium (ADGC),; European Alzheimer’s Disease Initiative (EADI), Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE), Genetic and Environmental Risk in AD/Defining Genetic, Polygenic and Environmental Risk for Alzheimer’s Disease Consortium (GERAD/PERADES), Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing. Nat Genet 2019;51(3):414-430.
  • 5. Ozaki K, Niida S. Genetic Background for Alzheimer's Disease: Knowledge Accumulated from AD GWAS. Brain Nerve 2019;71(10):1039-1051.
  • 6. 2019 Alzheimer’s Disease Facts and Figures. Alzheimers Dement 2019;15(3):32)
  • 7. Toledo JB, Arnold M, Kastenmüller G, et al. Alzheimer's Disease Neuroimaging Initiative and the Alzheimer Disease Metabolomics Consortium. Metabolic network failures in Alzheimer's disease: A biochemical road map. Alzheimers Dement 2017;13(9):965-984.
  • 8. Clarke JR, Ribeiro FC, Frozza RL, et al. Metabolic Dysfunction in Alzheimer's Disease: From Basic Neurobiology to Clinical Approaches. J Alzheimers Dis 2018;64(s1):S405-S426.
  • 9. Kapogiannis D, Mattson MP. Disrupted energy metabolism and neuronal circuit dysfunction in cognitive impairment and Alzheimer's disease. Lancet Neurol 2011;10(2):187-98.
  • 10. Craft S. The role of metabolic disorders in Alzheimer disease and vascular dementia: two roads converged. Arch Neurol 2009;66(3):300-5. 11. Majd S, Power J, Majd Z. Alzheimer's Disease and Cancer: When Two Monsters Cannot Be Together. Front Neurosci 2019;13:155.
  • 12. Frain L, Swanson D, Cho K, et al. Association of cancer and Alzheimer's disease risk in a national cohort of veterans. Alzheimers Dement 2017;13(12):1364-1370.
  • 13. Musicco M, Adorni F, Di Santo S, et al. Inverse occurrence of cancer and Alzheimer disease: a population-based incidence study. Neurology 2013 23;81(4):322-8.
  • 14. Driver JA, Beiser A, Au R, et al. Inverse association between cancer and Alzheimer's disease: results from the Framingham Heart Study. BMJ 2012;344:e1442.
  • 15. Catalá-López F, Suárez-Pinilla M, Suárez-Pinilla P, et al. Inverse and direct cancer comorbidity in people with central nervous system disorders: a meta-analysis of cancer incidence in 577,013 participants of 50 observational studies. Psychother Psychosom 2014;83(2):89-105.
  • 16. Roe CM, Behrens MI, Xiong C, et al. Alzheimer disease and cancer. Neurology 2005;64(5):895-8.
  • 17. Roe CM, Fitzpatrick AL, Xiong C, et al. Cancer linked to Alzheimer disease but not vascular dementia. Neurology 2010;74(2):106-12.
  • 18. Ou SM, Lee YJ, Hu YW, et al. Does Alzheimer's disease protect against cancers? A nationwide population based study. Neuroepidemiology 2013;40(1):42-9.
  • 19. Lee JE, Kim D, Lee JH. Association between Alzheimer's Disease and Cancer Risk in South Korea: an 11-year Nationwide Population-Based Study. Dement Neurocogn Disord 2018;17(4):137-147.
  • 20. Zhang Q, Guo S, Zhang X, et al. Inverse relationship between cancer and Alzheimer's disease: a systemic review meta-analysis. Neurol Sci 2015;36(11):1987-94.
  • 21. Shafi O. Inverse relationship between Alzheimer's disease and cancer, and other factors contributing to Alzheimer's disease: a systematic review. BMC Neurol 2016;16(1):236.
  • 22. Nudelman KNH, McDonald BC, Lahiri DK, Saykin AJ. Biological Hallmarks of Cancer in Alzheimer's Disease. Mol Neurobiol 2019;56(10):7173-7187.
  • 23. Behrens MI, Lendon C, Roe CM. A common biological mechanism in cancer and Alzheimer's disease? Curr Alzheimer Res 2009;6(3):196-204.
  • 24. Lehrer S. Glioma and Alzheimer's Disease. J Alzheimers Dis Rep 2018;2(1):213-218.
  • 25. Lehrer S, Rheinstein PH. Alzheimer's Disease Susceptibility Genes in Malignant Breast Tumors. Cancer Transl Med 2019;5(2):42-46.
  • 26. Holohan KN, Lahiri DK, Schneider BP, Foroud T, Saykin AJ. Functional microRNAs in Alzheimer's disease and cancer: differential regulation of common mechanisms and pathways. Front Genet 2013;3:323.
  • 27. Nagaraj S, Zoltowska KM, Laskowska-Kaszub K, Wojda U. microRNA diagnostic panel for Alzheimer's disease and epigenetic trade-off between neurodegeneration and cancer. Ageing Res Rev 2019;49:125-143.
  • 28. Monacelli F, Cea M, Borghi R, Odetti P, Nencioni A. Do Cancer Drugs Counteract Neurodegeneration? Repurposing for Alzheimer's Disease. J Alzheimers Dis 2017;55(4):1295–1306. 29. Vargas DM, De Bastiani MA, Zimmer ER, Klamt F. Alzheimer's disease master regulators analysis: search for potential molecular targets and drug repositioning candidates. Alzheimers Res Ther 2018;10(1):59.
  • 30. Clough E, Barrett T. The Gene Expression Omnibus Database. Methods Mol Biol 2016;1418:93-110.
  • 31. Mahi NA, Najafabadi MF, Pilarczyk M, Kouril M, Medvedovic M. GREIN: An Interactive Web Platform for Re-analyzing GEO RNA-seq Data. Sci Rep 2019;9(1):7580.
  • 32. Szklarczyk D, Gable AL, Lyon D, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res 2019;47(D1):D607-D613.
  • 33. Chin CH, Chen SH, Wu HH, Ho CW, Ko MT, Lin CY. cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst Biol 2014;8 Suppl 4:S11.
  • 34. Ideker T, Sharan R. Protein networks in disease. Genome Res 2008;18(4):644-52. 35. Xia J, Gill EE, Hancock RE. NetworkAnalyst for statistical, visual and network-based meta-analysis of gene expression data. Nat Protoc 2015;10(6):823-44.
  • 36. Tokar T, Pastrello C, Rossos AEM, et al. mirDIP 4.1-integrative database of human microRNA target predictions. Nucleic Acids Res 2018;46(D1):D360-D370.
  • 37. Seddighi S, Houck AL, Rowe JB, Pharoah PDP. Evidence of a Causal Association Between Cancer and Alzheimer's Disease: a Mendelian Randomization Analysis. Sci Rep 2019;9(1):13548.
  • 38. Ibáñez K, Boullosa C, Tabarés-Seisdedos R, Baudot A, Valencia A. Molecular evidence for the inverse comorbidity between central nervous system disorders and cancers detected by transcriptomic meta-analyses. PLoS Genet 2014;10(2):e1004173.
  • 39. Lehrer S, Rheinstein PH. Alzheimer's Disease Susceptibility Genes in Malignant Breast Tumors. Cancer Transl Med 2019;5(2):42-46.
  • 40. Sánchez-Valle J, Tejero H, Ibáñez K, et al. A molecular hypothesis to explain direct and inverse co-morbidities between Alzheimer’s Disease, Glioblastoma and Lung cancer Sci Rep 2017;7(1):4474.
  • 41. Battaglia C, Venturin M, Sojic A, et al. Candidate Genes and MiRNAs Linked to the Inverse Relationship Between Cancer and Alzheimer's Disease: Insights From Data Mining and Enrichment Analysis. Front Genet 2019;10:846.
  • 42. Tunissiolli NM, Castanhole-Nunes MMU, Biselli-Chicote PM, et al. Hepatocellular Carcinoma: a Comprehensive Review of Biomarkers, Clinical Aspects, and Therapy. Asian Pac J Cancer Prev 2017;18(4):863-872.
  • 43. Kinney JW, Bemiller SM, Murtishaw AS, Leisgang AM, Salazar AM, Lamb BT. Inflammation as a central mechanism in Alzheimer's disease. Alzheimers Dement (N Y) 2018;4:575–590.
  • 44. Newcombe EA, Camats-Perna J, Silva ML, Valmas N, Huat TJ, Medeiros R. Inflammation: the link between comorbidities, genetics, and Alzheimer's disease. J Neuroinflammation 2018;15(1):276.
  • 45. Heppner FL, Ransohoff RM, Becher B. Immune attack: the role of inflammation in Alzheimer disease. Nat Rev Neurosci 2015;16(6):358-372.
  • 46. Keenan BP, Fong L, Kelley RK. Immunotherapy in hepatocellular carcinoma: the complex interface between inflammation, fibrosis, and the immune response. J Immunother Cancer 2019;7(1):267.
  • 47. Bishayee A. The role of inflammation and liver cancer. Adv Exp Med Biol 2014;816:401-435.
  • 48. Yu LX, Ling Y, Wang HY. Role of nonresolving inflammation in hepatocellular carcinoma development and progression. NPJ Precis Oncol 2018;2(1):6.
  • 49. Garrido C, Paco L, Romero I, et al. MHC class I molecules act as tumor suppressor genes regulating the cell cycle gene expression, invasion and intrinsic tumorigenicity of melanoma cells. Carcinogenesis 2012;33(3):687-693.
  • 50. Garrido F. MHC/HLA Class I Loss in Cancer Cells. Adv Exp Med Biol 2019;1151:15-78.
  • 51. Axelrod ML, Cook RS, Johnson DB, Balko JM. Biological Consequences of MHC-II Expression by Tumor Cells in Cancer. Clin Cancer Res 2019;25(8):2392-2402
  • 52. Ciccocioppo F, Lanuti P, Pierdomenico L, et al. The Characterization of Regulatory T-Cell Profiles in Alzheimer's Disease and Multiple Sclerosis. Sci Rep 2019;9(1):8788.
  • 53. Chitnis T, Weiner HL. CNS inflammation and neurodegeneration. J Clin Invest 2017;127(10):3577-3587.
  • 54. Nataf S. Autoimmunity as a Driving Force of Cognitive Evolution. Front Neurosci 2017;11:582.
  • 55. Baruch K, Rosenzweig N, Kertser A, et al. Breaking immune tolerance by targeting Foxp3(+) regulatory T cells mitigates Alzheimer's disease pathology. Nat Commun 2015;6:7967.
  • 56. Guo P, Ma X, Zhao W, et al. TRIM31 is upregulated in hepatocellular carcinoma and promotes disease progression by inducing ubiquitination of TSC1-TSC2 complex. Oncogene 2018;37(4):478-488.
  • 57. Yang Y, Wang H, Kouadir M, Song H, Shi F. Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors. Cell Death Dis 2019;10(2):128.
  • 58. Yin J, Zhao F, Chojnacki JE, et al. NLRP3 Inflammasome Inhibitor Ameliorates Amyloid Pathology in a Mouse Model of Alzheimer's Disease. Mol Neurobiol 2018;55(3):1977-1987.
  • 59. Danborg PB, Simonsen AH, Waldemar G, Heegaard NH. The potential of microRNAs as biofluid markers of neurodegenerative diseases-a systematic review. Biomarkers 2014;19(4):259-268.
  • 60. Van Giau V, An SS. Emergence of exosomal miRNAs as a diagnostic biomarker for Alzheimer's disease. J Neurol Sci 2016;360:141-152.
  • 61. Tan W, Liu B, Qu S, Liang G, Luo W, Gong C. MicroRNAs and cancer: Key paradigms in molecular therapy. Oncol Lett 2018;15(3):2735-2742.
  • 62. Zhang ZQ, Meng H, Wang N, et al. Serum microRNA 143 and microRNA 215 as potential biomarkers for the diagnosis of chronic hepatitis and hepatocellular carcinoma. Diagn Pathol 2014;9:135.
  • 63. Dong H, Li J, Huang L, et al. Serum MicroRNA Profiles Serve as Novel Biomarkers for the Diagnosis of Alzheimer's Disease. Dis Markers 2015;2015:625659.
  • 64. Cheng L, Doecke JD, Sharples RA, et al. Australian Imaging, Biomarkers and Lifestyle (AIBL) Research Group. Prognostic serum miRNA biomarkers associated with Alzheimer's disease shows concordance with neuropsychological and neuroimaging assessment. Mol Psychiatry 2015;20(10):1188-1196.
Toplam 61 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Biyokimya ve Hücre Biyolojisi (Diğer), Onkoloji ve Karsinogenez, Nöroloji ve Nöromüsküler Hastalıklar
Bölüm Özgün Araştırma Makaleleri
Yazarlar

Dilek Pirim 0000-0002-0522-9432

Ecem Yilmaz Bu kişi benim 0000-0002-3486-7994

Yayımlanma Tarihi 1 Ağustos 2020
Kabul Tarihi 8 Temmuz 2020
Yayımlandığı Sayı Yıl 2020 Cilt: 46 Sayı: 2

Kaynak Göster

APA Pirim, D., & Yilmaz, E. (2020). Geç Başlangıçlı Alzheimer Hastalığı ve Hepatosellüler Karsinom ile İlişkili Ortak Moleküler Yolakların ve Anahtar Biyobelirteçlerin Biyoinformatik Analizlerle Araştırılması. Uludağ Üniversitesi Tıp Fakültesi Dergisi, 46(2), 161-168. https://doi.org/10.32708/uutfd.738750
AMA Pirim D, Yilmaz E. Geç Başlangıçlı Alzheimer Hastalığı ve Hepatosellüler Karsinom ile İlişkili Ortak Moleküler Yolakların ve Anahtar Biyobelirteçlerin Biyoinformatik Analizlerle Araştırılması. Uludağ Tıp Derg. Ağustos 2020;46(2):161-168. doi:10.32708/uutfd.738750
Chicago Pirim, Dilek, ve Ecem Yilmaz. “Geç Başlangıçlı Alzheimer Hastalığı Ve Hepatosellüler Karsinom Ile İlişkili Ortak Moleküler Yolakların Ve Anahtar Biyobelirteçlerin Biyoinformatik Analizlerle Araştırılması”. Uludağ Üniversitesi Tıp Fakültesi Dergisi 46, sy. 2 (Ağustos 2020): 161-68. https://doi.org/10.32708/uutfd.738750.
EndNote Pirim D, Yilmaz E (01 Ağustos 2020) Geç Başlangıçlı Alzheimer Hastalığı ve Hepatosellüler Karsinom ile İlişkili Ortak Moleküler Yolakların ve Anahtar Biyobelirteçlerin Biyoinformatik Analizlerle Araştırılması. Uludağ Üniversitesi Tıp Fakültesi Dergisi 46 2 161–168.
IEEE D. Pirim ve E. Yilmaz, “Geç Başlangıçlı Alzheimer Hastalığı ve Hepatosellüler Karsinom ile İlişkili Ortak Moleküler Yolakların ve Anahtar Biyobelirteçlerin Biyoinformatik Analizlerle Araştırılması”, Uludağ Tıp Derg, c. 46, sy. 2, ss. 161–168, 2020, doi: 10.32708/uutfd.738750.
ISNAD Pirim, Dilek - Yilmaz, Ecem. “Geç Başlangıçlı Alzheimer Hastalığı Ve Hepatosellüler Karsinom Ile İlişkili Ortak Moleküler Yolakların Ve Anahtar Biyobelirteçlerin Biyoinformatik Analizlerle Araştırılması”. Uludağ Üniversitesi Tıp Fakültesi Dergisi 46/2 (Ağustos 2020), 161-168. https://doi.org/10.32708/uutfd.738750.
JAMA Pirim D, Yilmaz E. Geç Başlangıçlı Alzheimer Hastalığı ve Hepatosellüler Karsinom ile İlişkili Ortak Moleküler Yolakların ve Anahtar Biyobelirteçlerin Biyoinformatik Analizlerle Araştırılması. Uludağ Tıp Derg. 2020;46:161–168.
MLA Pirim, Dilek ve Ecem Yilmaz. “Geç Başlangıçlı Alzheimer Hastalığı Ve Hepatosellüler Karsinom Ile İlişkili Ortak Moleküler Yolakların Ve Anahtar Biyobelirteçlerin Biyoinformatik Analizlerle Araştırılması”. Uludağ Üniversitesi Tıp Fakültesi Dergisi, c. 46, sy. 2, 2020, ss. 161-8, doi:10.32708/uutfd.738750.
Vancouver Pirim D, Yilmaz E. Geç Başlangıçlı Alzheimer Hastalığı ve Hepatosellüler Karsinom ile İlişkili Ortak Moleküler Yolakların ve Anahtar Biyobelirteçlerin Biyoinformatik Analizlerle Araştırılması. Uludağ Tıp Derg. 2020;46(2):161-8.

ISSN: 1300-414X, e-ISSN: 2645-9027

Uludağ Üniversitesi Tıp Fakültesi Dergisi "Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License" ile lisanslanmaktadır.


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Journal of Uludag University Medical Faculty is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

2023