RESUMEN
Malignancies dependent on hormone homeostasis include breast, ovary, cervical, prostate, testis and uterine tumors. Hormones are involved in signal transduction which orchestrate processes, such as apoptosis, proliferation, cell cycle or cytoskeleton organization. Currently, there is a need for novel biomarkers which would help to diagnose cancers efficiently. In this study, the genes implicated in signaling that is important in hormone-sensitive carcinogenesis were investigated regarding their prognostic significance. Data of seven cancer cohorts were collected from FireBrowse. 54 gene sets implicated in specific pathways were browsed through MSig database. Profiling was assessed via Monocle3, while gene ontology through PANTHER. For confirmation, correlation analysis was performed using WGCNA. Protein-protein networks were visualized via Cytoscape and impact of genes on survival, as well as cell cycle or cytoskeleton-related prognostic signatures, was tested. Several differences in expression profile were identified, some of them allowed to distinguish histology. Functional annotation revealed that various regulation of cell cycle, adhesion, migration, apoptosis and angiogenesis underlie these differences. Clinical traits, such as histological type or cancer staging, were found during evaluation of module-trait relationships. Of modules, the TopHubs (COL6A3, TNR, GTF2A1, NKX3-1) interacted directly with, e.g., PDGFB, ITGA10, SP1 or AKT3. Among TopHubs and interacting proteins, many showed an impact on hazard ratio and affected the cell cycle or cytoskeleton-related prognostic signatures, e.g., COL1A1 or PDGFB. In conclusion, this study laid the foundation for further hormone-sensitive carcinogenesis research through identification of genes which prove that crosstalk between cell cycle and cytoskeleton exists, opening avenues for future therapeutic strategies.
Asunto(s)
Neoplasias Hormono-Dependientes , Neoplasias , Biomarcadores , Carcinogénesis/genética , Ciclo Celular/genética , Biología Computacional , Citoesqueleto/genética , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Hormonas , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias Hormono-Dependientes/genética , Proteínas Proto-Oncogénicas c-sis/genética , Transducción de Señal/genéticaRESUMEN
The diminishing supply and increasing costs of donated blood have motivated research into novel hemoglobin-based oxygen carriers (HBOCs) that can serve as red blood cell (RBC) substitutes. HBOCs are versatile agents that can be used in the treatment of hemorrhagic shock. However, many of the RBC substitutes that are based on mammalian hemoglobins have presented key limitations such as instability and toxicity. In contrast, erythrocruorins (Ecs) are other types of HBOCs that may not suffer these disadvantages. Ecs are giant metalloproteins found in annelids, crustaceans, and some other invertebrates. Thus far, the Ecs of Lumbricus terrestris (LtEc) and Arenicola marina (AmEc) are the most thoroughly studied. Based on data from preclinical transfusion studies, it was found that these compounds not only efficiently transport oxygen and have anti-inflammatory properties, but also can be modified to further increase their effectiveness. This literature review focuses on the structure, properties, and application of Ecs, as well as their advantages over other HBOCs. Development of methods for both the stabilization and purification of erythrocruorin could confer to enhanced access to artificial blood resources.