The Role of Systems Biology in Deciphering Asthma Heterogeneity

Asthma is one of the most common and lifelong and chronic inflammatory diseases characterized by inflammation, bronchial hyperresponsiveness, and airway obstruction episodes. It is a heterogeneous disease of varying and overlapping phenotypes with many confounding factors playing a role in disease susceptibility and management. Such multifactorial disorders will benefit from using systems biology as a strategy to elucidate molecular insights from complex, quantitative, massive clinical, and biological data that will help to understand the underlying disease mechanism, early detection, and treatment planning. Systems biology is an approach that uses the comprehensive understanding of living systems through bioinformatics, mathematical, and computational techniques to model diverse high-throughput molecular, cellular, and the physiologic profiling of healthy and diseased populations to define biological processes. The use of systems biology has helped understand and enrich our knowledge of asthma heterogeneity and molecular basis; however, such methods have their limitations. The translational benefits of these studies are few, and it is recommended to reanalyze the different studies and omics in conjugation with one another which may help understand the reasons for this variation and help overcome the limitations of understanding the heterogeneity in asthma pathology. In this review, we aim to show the different factors that play a role in asthma heterogeneity and how systems biology may aid in understanding and deciphering the molecular basis of asthma

Understanding the Role of Innate Immune Cells and Identifying Genes in Breast Cancer Microenvironment

The innate immune system is the first line of defense against invading pathogens and has a major role in clearing transformed cells, besides its essential role in activating the adaptive immune system. Macrophages, dendritic cells, NK cells, and granulocytes are part of the innate immune system that accumulate in the tumor microenvironment such as breast cancer. These cells induce inflammation in situ by secreting cytokines and chemokines that promote tumor growth and progression, in addition to orchestrating the activities of other immune cells. In breast cancer microenvironment, innate immune cells are skewed towards immunosuppression that may lead to tumor evasion. However, the mechanisms by which immune cells could interact with breast cancer cells are complex and not fully understood. Therefore, the importance of the mammary tumor microenvironment in the development, growth, and progression of cancer is widely recognized. With the advances of using bioinformatics and analyzing data from gene banks, several genes involved in NK cells of breast cancer individuals have been identified. In this review, we discuss the activities of certain genes involved in the cross-talk among NK cells and breast cancer. Consequently, altering tumor immune microenvironment can make breast tumors more responsive to immunotherapy

Understanding the Role of Innate Immune Cells and Identifying Genes in Breast Cancer Microenvironment

The innate immune system is the first line of defense against invading pathogens and has a major role in clearing transformed cells, besides its essential role in activating the adaptive immune system. Macrophages, dendritic cells, NK cells, and granulocytes are part of the innate immune system that accumulate in the tumor microenvironment such as breast cancer. These cells induce inflammation in situ by secreting cytokines and chemokines that promote tumor growth and progression, in addition to orchestrating the activities of other immune cells. In breast cancer microenvironment, innate immune cells are skewed towards immunosuppression that may lead to tumor evasion. However, the mechanisms by which immune cells could interact with breast cancer cells are complex and not fully understood. Therefore, the importance of the mammary tumor microenvironment in the development, growth, and progression of cancer is widely recognized. With the advances of using bioinformatics and analyzing data from gene banks, several genes involved in NK cells of breast cancer individuals have been identified. In this review, we discuss the activities of certain genes involved in the cross-talk among NK cells and breast cancer. Consequently, altering tumor immune microenvironment can make breast tumors more responsive to immunotherapy

DKK3 protective role in prostate cancer is partly due to the modulation of immune-related pathways

      While it is considered one of the most common cancers and the leading cause of death in men worldwide, prognostic stratification and treatment modalities are still limited for patients with prostate cancer (PCa). Recently, the introduction of genomic profiling, as well as, the use of new techniques like next-generation sequencing (NGS) in many cancers provides novel tools for the discovery of new molecular targets that might improve our understanding of the genomic aberrations in PCa and the discovery of novel prognostic and therapeutic targets. In this study, we investigated the possible mechanisms through which Dickkopf-3 (DKK3) produces its possible protective role in prostate cancer using NGS in both the DKK3 overexpression PCa cell line (PC3) model, as well as, our patients’ cohort consisting of 9 prostate cancer and 5 benign prostatic hyperplasia. Interestingly, our results have shown that DKK3 transfection-modulated genes are involved in the regulation of cell motility, senescence-associated secretory phenotype (SASP), and cytokine signaling in the immune system, as well as, in the regulation of adaptive immune response. Further analysis of our NGS using our in vitro model revealed the presence of 36 differentially expressed genes between DKK3 transfected cells and PC3 empty vector. In addition, both CP and ACE2 genes were differentially expressed not only between the transfected and empty group but also between the transfected and mock cells. The top common differentially expressed genes (DEGs) between the DKK3 overexpression cell line and in our patients’ cohort showed the list of the following; IL32, IRAK1, RIOK1, HIST1H2BB, SNORA31, AKR1B1, ACE2 and CP. The upregulated genes including IL32, HIST1H2BB and SNORA31 showed tumor suppressor functions in various cancers including PCa. On the other hand, both IRAK1 and RIOK1 were downregulated and involved in tumor initiation, tumor progression, poor outcome and radiotherapy resistance.  Together, our results highlighted the possible role of the DKK3 related genes in protecting against PCa initiation and progression.</p