Soft Tissue Ewing Sarcoma Cell Drug Resistance Revisited: A Systems Biology Approach.

Ewing sarcoma is a rare type of cancer that develops in the bones and soft tissues. Drug therapy represents an extensively used modality for the treatment of sarcomas. However, cancer cells tend to develop resistance to antineoplastic agents, thereby posing a major barrier in treatment effectiveness. Thus, there is a need to uncover the molecular mechanisms underlying chemoresistance in sarcomas and, hence, to enhance the anticancer treatment outcome. In this study, a differential gene expression analysis was conducted on high-throughput transcriptomic data of chemoresistant versus chemoresponsive Ewing sarcoma cells. By applying functional enrichment analysis and protein-protein interactions on the differentially expressed genes and their corresponding products, we uncovered genes with a hub role in drug resistance. Granted that non-coding RNA epigenetic regulators play a pivotal role in chemotherapy by targeting genes associated with drug response, we investigated the non-coding RNA molecules that potentially regulate the expression of the detected chemoresistance genes. Of particular importance, some chemoresistance-relevant genes were associated with the autonomic nervous system, suggesting the involvement of the latter in the drug response. The findings of this study could be taken into consideration in the clinical setting for the accurate assessment of drug response in sarcoma patients and the application of tailored therapeutic strategies.

Identification of neoplasm-specific signatures of miRNA interactions by employing a systems biology approach.

MicroRNAs represent major regulatory components of the disease epigenome and they constitute powerful biomarkers for the accurate diagnosis and prognosis of various diseases, including cancers. The advent of high-throughput technologies facilitated the generation of a vast amount of miRNA-cancer association data. Computational approaches have been utilized widely to effectively analyze and interpret these data towards the identification of miRNA signatures for diverse types of cancers. Herein, a novel computational workflow was applied to discover core sets of miRNA interactions for the major groups of neoplastic diseases by employing network-based methods. To this end, miRNA-cancer association data from four comprehensive publicly available resources were utilized for constructing miRNA-centered networks for each major group of neoplasms. The corresponding miRNA-miRNA interactions were inferred based on shared functionally related target genes. The topological attributes of the generated networks were investigated in order to detect clusters of highly interconnected miRNAs that form core modules in each network. Those modules that exhibited the highest degree of mutual exclusivity were selected from each graph. In this way, neoplasm-specific miRNA modules were identified that could represent potential signatures for the corresponding diseases.

A Counterintuitive Neutrophil-Mediated Pattern in COVID-19 Patients Revealed through Transcriptomics Analysis.

The COVID-19 pandemic has persisted for almost three years. However, the mechanisms linked to the SARS-CoV-2 effect on tissues and disease severity have not been fully elucidated. Since the onset of the pandemic, a plethora of high-throughput data related to the host transcriptional response to SARS-CoV-2 infections has been generated. To this end, the aim of this study was to assess the effect of SARS-CoV-2 infections on circulating and organ tissue immune responses. We profited from the publicly accessible gene expression data of the blood and soft tissues by employing an integrated computational methodology, including bioinformatics, machine learning, and natural language processing in the relevant transcriptomics data. COVID-19 pathophysiology and severity have mainly been associated with macrophage-elicited responses and a characteristic "cytokine storm". Our counterintuitive findings suggested that the COVID-19 pathogenesis could also be mediated through neutrophil abundance and an exacerbated suppression of the immune system, leading eventually to uncontrolled viral dissemination and host cytotoxicity. The findings of this study elucidated new physiological functions of neutrophils, as well as tentative pathways to be explored in asymptomatic-, ethnicity- and locality-, or staging-associated studies.