Main Article Content

Abstract

Myocardial infarction, resulting from coronary blood vessel blockage, inflicts lasting damage on the heart muscle. Meanwhile, breast cancer ranks among the most diagnosed cancers, causing millions of deaths annually. Mouse model research suggests that myocardial infarction induces systemic changes, fostering cross-disease communication that expedites breast cancer. Using GEO2R for transcriptomic analysis, Cytoscape for protein-protein interaction (PPI), and EnrichR for enrichment analysis, we explored the myocardial infarction-breast cancer relationship with datasets from GEO. We identified 3,300 differentially expressed genes, including 6 commonly upregulated and 18 commonly downregulated genes. PPI and enrichment analyses revealed RAD51 genes associated with homologous recombination pathways (P-value 0.02032). Additionally, 4 genes (RAD51, KIF4A, DTL, and DLGAP5) were linked to CD105+ endothelial cells (P-value 0.00002216), connecting myocardial infarction and breast cancer. Nevertheless, further testing is needed for accurate results and to support this study's transcriptomic analysis.

Keywords

Myocardial infarction, transcriptomic, breast cancer, protein interaction, cytoscape

Article Details

How to Cite
1.
Miftahul Khair Akbar, Fadilah Fadilah, Arief Aulia Rahman. Connecting the Dots: Transcriptomic Approaches and Relationship between Myocardial Infarction and Breast Cancer. EKSAKTA [Internet]. 2024Mar.30 [cited 2024Apr.22];25(01):111-25. Available from: https://eksakta.ppj.unp.ac.id/index.php/eksakta/article/view/478

References

  1. Ali, S., Ishaq Dar, M., A. Rather, R., & Afroze, D. (2020). Cell Cycle and Factors Involved in Inhibition or Progression of Breast Cancer. In Breast Cancer Biology. IntechOpen.
  2. Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., Davis, A. P., Dolinski, K., Dwight, S. S., Eppig, J. T., Harris, M. A., Hill, D. P., Issel-Tarver, L., Kasarskis, A., Lewis, S., Matese, J. C., Richardson, J. E., Ringwald, M., Rubin, G. M., & Sherlock, G. (2000). Gene Ontology: tool for the unification of biology. Nature Genetics, 25(1), 25–29.
  3. Attachaipanich, T., Chattipakorn, S. C., & Chattipakorn, N. (2024). Current evidence regarding the cellular mechanisms associated with cancer progression due to cardiovascular diseases. Journal of Translational Medicine, 22(1), 105.
  4. Bedford, L., Lowe, J., Dick, L. R., Mayer, R. J., & Brownell, J. E. (2011). Ubiquitin-like protein conjugation and the ubiquitin–proteasome system as drug targets. Nature Reviews Drug Discovery, 10(1), 29–46.
  5. Borys, F., Joachimiak, E., Krawczyk, H., & Fabczak, H. (2020). Intrinsic and Extrinsic Factors Affecting Microtubule Dynamics in Normal and Cancer Cells. Molecules, 25(16), 3705.
  6. Caporizzo, M. A., Chen, C. Y., & Prosser, B. L. (2019). Cardiac microtubules in health and heart disease. Experimental Biology and Medicine, 244(15), 1255–1272.
  7. Caporizzo, M. A., & Prosser, B. L. (2022). The microtubule cytoskeleton in cardiac mechanics and heart failure. Nature Reviews Cardiology, 19(6), 364–378.
  8. Charpin, C., Dales, J.-P., Garcia, S., Carpentier, S., Djemli, A., Andrac, L., Lavaut, M.-N., Allasia, C., & Bonnier, P. (2004). Tumor Neoangiogenesis by CD31 and CD105 Expression Evaluation in Breast Carcinoma Tissue Microarrays. Clinical Cancer Research, 10(17), 5815–5819.
  9. Clough, E., & Barrett, T. (2016). The Gene Expression Omnibus Database (pp. 93–110).
  10. Consortium, T. G. O. (2001). Creating the Gene Ontology Resource: Design and Implementation. Genome Research, 11(8), 1425–1433.
  11. Deng, Y., Li, J., Zhang, Y., Hu, H., Wan, F., Min, H., Zhou, H., Gu, L., Liao, X., Zhou, J., & Zhou, J. (2023). NUF2 Promotes Breast Cancer Development as a New Tumor Stem Cell Indicator. International Journal of Molecular Sciences, 24(4), 4226.
  12. Feng, C., Zhang, Y., Wu, F., Li, J., Liu, M., Lv, W., Li, C., Wang, W., Tan, Q., Xue, X., Ma, X., & Zhang, S. (2023). Relationship between homologous recombination deficiency and clinical features of breast cancer based on genomic scar score. The Breast, 69, 392–400.
  13. Hakiminia, F., Jannat Alipoor, F., Keshavarz, M., & Asadi, M. H. (2023). LncRNA PNKY Is Upregulated in Breast Cancer and Promotes Cell Proliferation and EMT in Breast Cancer Cells. Non-Coding RNA, 9(2), 25.
  14. Hausenloy, D. J., Bøtker, H. E., Ferdinandy, P., Heusch, G., Ng, G. A., Redington, A., & Garcia-Dorado, D. (2019). Cardiac innervation in acute myocardial ischaemia/reperfusion injury and cardioprotection. Cardiovascular Research, 115(7), 1167–1177.
  15. Hu, Q., & Huang, T. (2023). Regulation of the Cell Cycle by ncRNAs Affects the Efficiency of CDK4/6 Inhibition. International Journal of Molecular Sciences, 24(10), 8939.
  16. Jeong, J., Suh, Y., & Jung, K. (2019). Context Drives Diversification of Monocytes and Neutrophils in Orchestrating the Tumor Microenvironment. Frontiers in Immunology, 10.
  17. Jian, Y., Zhou, X., Shan, W., Chen, C., Ge, W., Cui, J., Yi, W., & Sun, Y. (2023). Crosstalk between macrophages and cardiac cells after myocardial infarction. Cell Communication and Signaling, 21(1), 109.
  18. Karra, H., Repo, H., Ahonen, I., Löyttyniemi, E., Pitkänen, R., Lintunen, M., Kuopio, T., Söderström, M., & Kronqvist, P. (2014). Cdc20 and securin overexpression predict short-term breast cancer survival. British Journal of Cancer, 110(12), 2905–2913.
  19. Kitada, M., Hayashi, S., Matsuda, Y., Ishibashi, K., Oikawa, K., & Miyokawa, N. (2014). Spindle cell carcinoma of the breast as complex cystic lesion: a case report. Cancer Biology & Medicine, 11(2), 130–133.
  20. Koelwyn, G. J., Newman, A. A. C., Afonso, M. S., van Solingen, C., Corr, E. M., Brown, E. J., Albers, K. B., Yamaguchi, N., Narke, D., Schlegel, M., Sharma, M., Shanley, L. C., Barrett, T. J., Rahman, K., Mezzano, V., Fisher, E. A., Park, D. S., Newman, J. D., Quail, D. F., … Moore, K. J. (2020). Myocardial infarction accelerates breast cancer via innate immune reprogramming. Nature Medicine, 26(9), 1452–1458.
  21. Kubota, A., & Frangogiannis, N. G. (2022). Macrophages in myocardial infarction. American Journal of Physiology-Cell Physiology, 323(4), C1304–C1324.
  22. Li, X., Zhang, L., Yi, Z., Zhou, J., Song, W., Zhao, P., Wu, J., Song, J., & Ni, Q. (2022). NUF2 Is a Potential Immunological and Prognostic Marker for Non-Small-Cell Lung Cancer. Journal of Immunology Research, 2022, 1–22.
  23. Li, Y., Wei, J., Sun, Y., Zhou, W., Ma, X., Guo, J., Zhang, H., & Jin, T. (2023). DLGAP5 Regulates the Proliferation, Migration, Invasion, and Cell Cycle of Breast Cancer Cells via the JAK2/STAT3 Signaling Axis. International Journal of Molecular Sciences, 24(21), 15819.
  24. Liu, Y., Li, J., Xu, N., Yu, H., Gong, L., Li, Q., Yang, Z., Li, S., Yang, J., Huang, D., Xue, Y., Xue, G., Liu, J., Chen, H., Zhang, R., Li, A., Zhao, Y., Li, P., Li, M., … Cai, B. (2022). Transcription factor Meis1 act as a new regulator of ischemic arrhythmias in mice. Journal of Advanced Research, 39, 275–289.
  25. Lu, L., Liu, M., Sun, R., Zheng, Y., & Zhang, P. (2015). Myocardial Infarction: Symptoms and Treatments. Cell Biochemistry and Biophysics, 72(3), 865–867.
  26. Łukasiewicz, S., Czeczelewski, M., Forma, A., Baj, J., Sitarz, R., & Stanisławek, A. (2021). Breast Cancer—Epidemiology, Risk Factors, Classification, Prognostic Markers, and Current Treatment Strategies—An Updated Review. Cancers, 13(17), 4287.
  27. Mantovani, A., Allavena, P., Marchesi, F., & Garlanda, C. (2022). Macrophages as tools and targets in cancer therapy. Nature Reviews Drug Discovery, 21(11), 799–820.
  28. Mao, S., Tian, S., Luo, X., Zhou, M., Cao, Z., & Li, J. (2021). Overexpression of PLK1 relieved the myocardial ischemia-reperfusion injury of rats through inducing the mitophagy and regulating the p-AMPK/FUNDC1 axis. Bioengineered, 12(1), 2676–2687.
  29. Mekonnen, N., Yang, H., & Shin, Y. K. (2022). Homologous Recombination Deficiency in Ovarian, Breast, Colorectal, Pancreatic, Non-Small Cell Lung and Prostate Cancers, and the Mechanisms of Resistance to PARP Inhibitors. Frontiers in Oncology, 12.
  30. Meurer, S. K., & Weiskirchen, R. (2020). Endoglin: An ‘Accessory’ Receptor Regulating Blood Cell Development and Inflammation. International Journal of Molecular Sciences, 21(23), 9247.
  31. Mondal, M., Conole, D., Nautiyal, J., & Tate, E. W. (2022). UCHL1 as a novel target in breast cancer: emerging insights from cell and chemical biology. British Journal of Cancer, 126(1), 24–33.
  32. Moore, X. T. R., Gheghiani, L., & Fu, Z. (2023). The Role of Polo-Like Kinase 1 in Regulating the Forkhead Box Family Transcription Factors. Cells, 12(9), 1344.
  33. Ng, B., Puspitaningtyas, H., Wiranata, J. A., Hutajulu, S. H., Widodo, I., Anggorowati, N., Sanjaya, G. Y., Lazuardi, L., & Sripan, P. (2023). Breast cancer incidence in Yogyakarta, Indonesia from 2008–2019: A cross-sectional study using trend analysis and geographical information system. PLOS ONE, 18(7), e0288073.
  34. Olingy, C. E., Dinh, H. Q., & Hedrick, C. C. (2019). Monocyte heterogeneity and functions in cancer. Journal of Leukocyte Biology, 106(2), 309–322.
  35. Orhan, E., Velazquez, C., Tabet, I., Sardet, C., & Theillet, C. (2021). Regulation of RAD51 at the Transcriptional and Functional Levels: What Prospects for Cancer Therapy? Cancers, 13(12), 2930.
  36. Parker, A. L., Kavallaris, M., & McCarroll, J. A. (2014). Microtubules and Their Role in Cellular Stress in Cancer. Frontiers in Oncology, 4.
  37. Parker, A. L., Teo, W. S., McCarroll, J. A., & Kavallaris, M. (2017). An Emerging Role for Tubulin Isotypes in Modulating Cancer Biology and Chemotherapy Resistance. International Journal of Molecular Sciences, 18(7), 1434.
  38. Phyo, S. A., Uchida, K., Chen, C. Y., Caporizzo, M. A., Bedi, K., Griffin, J., Margulies, K., & Prosser, B. L. (2022). Transcriptional, Post-Transcriptional, and Post-Translational Mechanisms Rewrite the Tubulin Code During Cardiac Hypertrophy and Failure. Frontiers in Cell and Developmental Biology, 10.
  39. Qi, J., Kim, H., Scortegagna, M., & Ronai, Z. A. (2013). Regulators and Effectors of Siah Ubiquitin Ligases. Cell Biochemistry and Biophysics, 67(1), 15–24.
  40. Qian, H., Yang, L., Zhao, W., Chen, H., & He, S. (2018). A comparison of CD105 and CD31 expression in tumor vessels of hepatocellular carcinoma by tissue microarray and flow cytometry. Experimental and Therapeutic Medicine.
  41. Rakha, E. A., Brogi, E., Castellano, I., & Quinn, C. (2022). Spindle cell lesions of the breast: a diagnostic approach. Virchows Archiv, 480(1), 127–145.
  42. Rossi, E., Bernabeu, C., & Smadja, D. M. (2019). Endoglin as an Adhesion Molecule in Mature and Progenitor Endothelial Cells: A Function Beyond TGF-β. Frontiers in Medicine, 6.
  43. Shyu, K.-G. (2017). The Role of Endoglin in Myocardial Fibrosis. Acta Cardiologica Sinica, 33(5), 461–467.
  44. Stewart, M. D., Merino Vega, D., Arend, R. C., Baden, J. F., Barbash, O., Beaubier, N., Collins, G., French, T., Ghahramani, N., Hinson, P., Jelinic, P., Marton, M. J., McGregor, K., Parsons, J., Ramamurthy, L., Sausen, M., Sokol, E. S., Stenzinger, A., Stires, H., … Allen, J. (2022). Homologous Recombination Deficiency: Concepts, Definitions, and Assays. The Oncologist, 27(3), 167–174.
  45. Su, J., Gao, C., Wang, R., Xiao, C., & Yang, M. (2018). Genes associated with inflammation and the cell cycle may serve as biomarkers for the diagnosis and prognosis of acute myocardial infarction in a Chinese population. Molecular Medicine Reports.
  46. Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71(3), 209–249.
  47. Supplitt, S., Karpinski, P., Sasiadek, M., & Laczmanska, I. (2021). Current Achievements and Applications of Transcriptomics in Personalized Cancer Medicine. International Journal of Molecular Sciences, 22(3), 1422.
  48. Thun, M. J., DeLancey, J. O., Center, M. M., Jemal, A., & Ward, E. M. (2010). The global burden of cancer: priorities for prevention. Carcinogenesis, 31(1), 100–110.
  49. Tsao, C. W., Aday, A. W., Almarzooq, Z. I., Anderson, C. A. M., Arora, P., Avery, C. L., Baker-Smith, C. M., Beaton, A. Z., Boehme, A. K., Buxton, A. E., Commodore-Mensah, Y., Elkind, M. S. V., Evenson, K. R., Eze-Nliam, C., Fugar, S., Generoso, G., Heard, D. G., Hiremath, S., Ho, J. E., … Martin, S. S. (2023). Heart Disease and Stroke Statistics—2023 Update: A Report From the American Heart Association. Circulation, 147(8).
  50. Verschuren, J. J. W., Trompet, S., Deelen, J., Stott, D. J., Sattar, N., Buckley, B. M., Ford, I., Heijmans, B. T., Guchelaar, H.-J., Houwing-Duistermaat, J. J., Slagboom, P. E., & Jukema, J. W. (2013). Non-Homologous End-Joining Pathway Associated with Occurrence of Myocardial Infarction: Gene Set Analysis of Genome-Wide Association Study Data. PLoS ONE, 8(2), e56262.
  51. Wang, H., Lu, C., Li, Q., Xie, J., Chen, T., Tan, Y., Wu, C., & Jiang, J. (2014). The Role of Kif4A in Doxorubicin-Induced Apoptosis in Breast Cancer Cells. Molecules and Cells, 37(11), 812–818.
  52. Wang, L., Liu, G., Bolor-Erdene, E., Li, Q., Mei, Y., & Zhou, L. (2021). Identification of KIF4A as a prognostic biomarker for esophageal squamous cell carcinoma. Aging, 13(21), 24050–24070.
  53. Wang, X., Shi, N., Wu, B., Yuan, L., Chen, J., Ye, C., & Hao, M. (2022). Bioinformatics analysis of gene expression profile and functional analysis in periodontitis and Parkinson’s disease. Frontiers in Aging Neuroscience, 14.
  54. Willis, M. S., Bevilacqua, A., Pulinilkunnil, T., Kienesberger, P., Tannu, M., & Patterson, C. (2014). The role of ubiquitin ligases in cardiac disease. Journal of Molecular and Cellular Cardiology, 71, 43–53.
  55. Wu, G., Zhou, L., Khidr, L., Guo, X. E., Kim, W., Lee, Y. M., Krasieva, T., & Chen, P.-L. (2008). A novel role of the chromokinesin Kif4A in DNA damage response. Cell Cycle, 7(13), 2013–2020.
  56. Xian, F., Zhao, C., Huang, C., Bie, J., & Xu, G. (2023). The potential role of CDC20 in tumorigenesis, cancer progression and therapy: A narrative review. Medicine, 102(36), e35038.
  57. Xie, Y.-P., Lai, S., Lin, Q.-Y., Xie, X., Liao, J.-W., Wang, H.-X., Tian, C., & Li, H.-H. (2018). CDC20 regulates cardiac hypertrophy via targeting LC3-dependent autophagy. Theranostics, 8(21), 5995–6007.
  58. Xu, T., Dong, M., Li, H., Zhang, R., & Li, X. (2020). Elevated mRNA expression levels of DLGAP5 are associated with poor prognosis in breast cancer. Oncology Letters.
  59. Xu, W., Wang, Y., Wang, Y., Lv, S., Xu, X., & Dong, X. (2019). Screening of differentially expressed genes and identification of NUF2 as a prognostic marker in breast cancer. International Journal of Molecular Medicine.
  60. Yan, L., Cui, Y., & Feng, J. (2023). Biology of Pellino1: a potential therapeutic target for inflammation in diseases and cancers. Frontiers in Immunology, 14.
  61. Yang, J., Tong, T., Zhu, C., Zhou, M., Jiang, Y., Chen, H., Que, L., Liu, L., Zhu, G., Ha, T., Chen, Q., Li, C., Xu, Y., Li, J., & Li, Y. (2022). Peli1 contributes to myocardial ischemia/reperfusion injury by impairing autophagy flux via its E3 ligase mediated ubiquitination of P62. Journal of Molecular and Cellular Cardiology, 173, 30–46.
  62. Yang, X., Kui, L., Tang, M., Li, D., Wei, K., Chen, W., Miao, J., & Dong, Y. (2020). High-Throughput Transcriptome Profiling in Drug and Biomarker Discovery. Frontiers in Genetics, 11.
  63. Yuan, Z., Li, Y., Zhang, S., Wang, X., Dou, H., Yu, X., Zhang, Z., Yang, S., & Xiao, M. (2023). Extracellular matrix remodeling in tumor progression and immune escape: from mechanisms to treatments. Molecular Cancer, 22(1), 48.
  64. Zangouei, A. S., Zangoue, M., Taghehchian, N., Zangooie, A., Rahimi, H. R., Saburi, E., Alavi, M. S., & Moghbeli, M. (2023). Cell cycle related long non-coding RNAs as the critical regulators of breast cancer progression and metastasis. Biological Research, 56(1), 1.
  65. Zhang, F., Li, L., & Fan, Z. (2022). circRNAs and their relationship with breast cancer: a review. World Journal of Surgical Oncology, 20(1), 373.
  66. Zhang, Q., Wu, J., Bai, X., & Liang, T. (2020). Evaluation of Intra-Tumoral Vascularization in Hepatocellular Carcinomas. Frontiers in Medicine, 7.
  67. Zheng, H., Qian, X., Tian, W., & Cao, L. (2022). Exploration of the Common Gene Characteristics and Molecular Mechanism of Parkinson’s Disease and Crohn’s Disease from Transcriptome Data. Brain Sciences, 12(6), 774.
  68. Zhu, K., Li, X., Gao, L., Ji, M., Huang, X., Zhao, Y., Diao, W., Fan, Y., Chen, X., Luo, P., Shen, L., & Li, L. (2023). Identification of Hub Genes Correlated with the Initiation and Development in Chronic Kidney Disease via Bioinformatics Analysis. Kidney and Blood Pressure Research, 48(1), 79–91.