Biology subjects

Crespo, D.

Publications and source records attributed to Crespo, D..

3 recordsLinked to original sources

bioRxiv2022

DNA Methylation Signatures in Breast Cancer: A Systematic Review and Meta-Analysis

Epigenetic changes are involved in the onset and progression of cancer, and the detection of DNA methylation signatures may foster the improvement of diagnosis and prognosis. While the emergence of innovative technologies has fostered numerous studies in breast cancer, many lack statistical power due to the small sample sizes generally involved. In this study, we present a novel meta-analysis that identifies a common pattern of DNA methylation in all breast cancer subtypes. We obtained DNA methylation signatures at the gene and biological function level, identifying those significant groups of genes and functional pathways affected. To achieve this, we conducted a thorough systematic review following PRISMA statement guidelines for the selection of studies on DNA methylation in breast cancer. In total, we gathered four studies (GSE52865, GSE141338, GSE59901 and GSE101443) that were split into 13 comparisons comprising a set of 144 individuals. We discovered that most breast cancer subtypes share a significant deregulation in the immune system and alterations to the cell cycle. This integrative approach combines all available information from public data repositories and possesses greater statistical power than any individual study. Further evaluations of the identified differential biological processes and pathways may support the identification of novel biomarkers and therapeutic targets. Simple summaryThe identification of DNA methylation patterns in breast cancer represents a potentially valuable approach in defining more accurate diagnoses and treatment options. In this study, we applied a novel methodology that integrates the DNA methylation profiles of all studies available in public repositories via systematic review and meta-analysis. The results provide evidence of a common DNA methylation signature in distinct breast cancer subtypes, which reflects a significant deregulation of the immune system and alterations to the cell cycle. Overall, these results may support the selection of disease/treatment biomarkers and the identification of therapeutic targets.

cancer biology↗

bioRxiv2019

The Caudate Nucleus Undergoes Dramatic and Unique Transcriptional Changes in Human Prodromal Huntington’s Disease Brain

The mechanisms underlying degeneration of the specific neurons in the striatum of Huntingons Disease (HD) brain are currently unknown. The striatum is massively degenerated in late stage HD, making examination of post-mortem brain tissue from symptomatic individuals problematic. Striatal tissue is largely intact in the brains of asymptomatic HD positive (HD+) gene carriers, but these samples are exceedingly rare. In this study, caudate nucleus (CAU) tissue from two asymptomatic HD+ individuals was subjected to high throughput mRNA sequencing (mRNA-Seq) for comparison with similar datasets from symptomatic HD individuals and healthy controls. The overall transcriptional response in HD+ CAU shares much of the same response observed in HD Brodmann Area 9 (BA9) samples, an area that is relatively spared from significant degeneration. A set of differentially expressed (DE) genes predominantly related to the heat shock response are found in common between brain regions, and show much higher induction in HD+ CAU than HD BA9. The most highly perturbed pathways show near complete agreement when comparing diseased tissue with control, and a random forest classifier predicted that the two HD+ CAU samples strongly resemble HD BA9 and not control BA9. Nonetheless, when genes were prioritized by their specificity to HD+ CAU, a large number of pathways spanning many biological processes emerged. Further comparison of HD+ BA9 with HD BA9 identified genes that may be early responders to disease, and have altered expression in symptomatic individuals. This study presents the first and largest examination of asymptomatic brain gene expression to date, and suggests many new avenues of investigation into the mechanisms underlying neurodegeneration in HD.

genomics↗

bioRxiv2018

Retinoic acid and androgens interact to regulate spermatogenesis in a non-mammalian vertebrate lacking stra8

In mammals, retinoic acid (RA) signaling is critical for spermatogonial differentiation and for entering meiosis, the latter depending on RA-induced Stra8 gene expression. Many fish species, including zebrafish, do not contain a stra8 gene, but RA signaling nevertheless is important for sperm production. However, it is not known which stages of spermatogenesis respond to RA. Here, we show in zebrafish that RA promotes spermatogonial differentiation and reduces the apoptotic loss of spermatids, but is not required for meiosis. Some of the RA effects are mediated by other genes, in particular rec8a. Surprisingly, androgens can partially compensate for the loss of RA signaling, and we identify a link between the endocrine system and RA signaling: follicle-stimulating hormone (Fsh) stimulates testicular RA production. While RA signaling is relevant at the basis of the vertebrates, it also targets processes and mechanisms that are different from those known in mammals so far.

developmental biology↗