Genes Co-Expressed with ESR2 Influence Clinical Outcomes in Cancer Patients: TCGA Data Analysis.

ERß has been assigned a tumor suppressor role in many cancer types. However, as conflicting findings emerge, ERß's tissue-specific expression and functional role have remained elusive. There remains a notable gap in compact and comprehensive analyses of ESR2 mRNA expression levels across diverse tumor types coupled with an exploration of its potential gene network. In this study, we aim to address these gaps by presenting a comprehensive analysis of ESR2 transcriptomic data. We distinguished cancer types with significant changes in ESR2 expression levels compared to corresponding healthy tissue and concluded that ESR2 influences patient survival. Gene Set Enrichment Analysis (GSEA) distinguished molecular pathways affected by ESR2, including oxidative phosphorylation and epithelial-mesenchymal transition. Finally, we investigated genes displaying similar expression patterns as ESR2 in tumor tissues, identifying potential co-expressed genes that may exert a synergistic effect on clinical outcomes, with significant results, including the expression of ACIN1, SYNE2, TNFRSF13C, and MDM4. Collectively, our results highlight the significant influence of ESR2 mRNA expression on the transcriptomic landscape and the overall metabolism of cancerous cells across various tumor types.

The RNA world: from experimental laboratory to "in silico" approach. Part 1: User friendly RNA expression databases portals.

Cellular information about "life instruction" is stored, transferred, and modified using different types of RNA molecules. During the last decades, a growing number of RNA data has been generated thanks to the development of microarray chips and next-generation sequencing (NGS) methods. Improvement of bioinformatics contributed to the discovery of many types of new non-coding RNAs (ncRNAs), mostly with regulatory functions that supplemented the knowledge about the world of RNA. All of it, as well as the Human Genome Project (HGP) and the Cancer Genome Atlas (TCGA) project, has resulted in the formation of data storage and analysis portals which are widely used in cancer research and moved science from in vitro to in silico research. In this review we presented and discussed the data storage and analysis portals used by us, such as cBioPortal, UALCAN, ENCORI, and others. During the revision of these sites, we paid attention to data integration, simplicity of analysis, and results visualization, which are important for users without bioinformatic or statistical skills. In our opinion, the RNA analysis online tools will rapidly develop during the next decade and it seems to be a way for personalization of cancer treatment.

The association between bromodomain proteins and cancer stemness in different solid tumor types.

Cancer stemness, which covers the stem cell-like molecular traits of cancer cells, is essential for tumor development, progression and relapse. Both transcriptional and epigenetic aberrations are essentially connected with cancer stemness. The engagement of bromodomain (BrD) proteins-a family of epigenetic factors-has been presented in the pathogenesis of several tumor types, although their association with cancer stemness remains largely unknown. Here, we harnessed TCGA and GEO databases and used several bioinformatic tools (ie, Oncomine, PrognoScan, GEPIA2, TIMER2.0, TISIDB, GSEA, R2 platform) to characterize the association between the BrD family members' expression and cancer stemness in solid tumors. Our results demonstrate that significant upregulation of ATAD2 and SMARCA4, and downregulation of SMARCA2 is consistently associated with enriched cancer stem cell-like phenotype, respectively. Especially, higher-grade tumors that display stem cell-like properties overexpress ATAD2. In contrast to most BrD members, the gene expression profiles of ATAD2HIGH expressing tumors are strongly enriched with known markers of stem cells and with specific targets for c-Myc transcription factor. For other BrD proteins, the association with cancer de-differentiation status is rather tumor-specific. Our results demonstrate for the first time the relation between distinct BrD family proteins and cancer stemness across 27 solid tumor types. Specifically, our approach allowed us to discover a robust association of high ATAD2 expression with cancer stemness and reveal its' versatility in tumors. As bromodomains are attractive targets from a chemical and structural perspective, we propose ATAD2 as a novel druggable target for de-differentiated tumors, especially those overexpressing MYC.

It Runs in the Bromodomain Family: Speckled Proteins (SP) Play a Role in the Antitumor Immune Response in Solid Tumors.

Cells and immune cells in the extracellular matrix: Depending on the tumor type and variety of TAAs (tumor-associated antigens), immune infiltrates are composed of many different subpopulations of immune cells. Epigenetic changes are also considered to be characteristic of cancer. Epigenetic factors taking part in the regulation of gene expression include the VII group of bromodomain proteins (BrD)-SP-family proteins. Here, we used transcriptomic data from the TCGA database, as well as immunological evidence from ESTIMATE, TIP, and TIMER2.0 databases for various solid tumor types and harnessed several publicly available bioinformatic tools (such as GSEA and GSCA) to demonstrate mechanisms and interactions between BrD proteins and immune infiltrates in cancer. We present a consistently positive correlation between the SP-family genes and immune score regardless of the tumor type. The SP-family proteins correlate positively with T cells' trafficking and infiltration into tumor. Our results also show an association between the high expression of SP family genes and enriched transcriptome profiles of inflammatory response and TNF-α signaling via NF-κß. We also show that the SP-family proteins could be considered good predictors of high immune infiltration phenotypes.