Gene Expression Profiling Studies Research Articles

MIG1, TUP1 and NRG1 mediated yeast to hyphal morphogenesis inhibition in Candida albicans by ganciclovir.

Candida albicans is a polymorphic human fungal pathogen and the prime etiological agent responsible for candidiasis. The main two aspects of C. albicans virulence that have been suggested are yeast-to-hyphal (Y-H) morphological transitions and biofilm development. Anti-fungal agents targeting these virulence attributes enhances the antifungal drug development process. Repositioning with other non-fungal drugs offered a one of the new strategies and a potential alternative option to counter the urgent need for antifungal drug development. In the current study, an antiviral drug ganciclovir was screened as an antifungal agent against ATCC 90028, 10231 and clinical isolate (C1). Ganciclovir at 0.5mg/ml concentration reduced 50% hyphal development on a silicon-based urinary catheter and was visualized using scanning electron microscopy. Ganciclovir reduced ergosterol biosynthesis in both strains and C1 isolate of C. albicans in a concentration-dependent manner. Additionally, a gene expression profile study showed that ganciclovir treatment resulted in upregulation of hyphal-specific repressors MIG1, TUP1, and NRG1 in C. albicans. Additionally, an in vivo study on the Bombyx mori silkworm model further evidenced the virulence inhibitory ability of ganciclovir (0.5mg/ml) against C. albicans. This is the first report that explore the novel anti-morphogenic activities of ganciclovir against the pathogenic C. albicans strains, along with clinical isolates. Further, ganciclovir may be considered for therapeutic purpose after combinations with standard antifungal agents.

Immunohistochemical profile of triple negative breast cancers: SOX10 and AR dual negative tumors have worse outcomes.

Triple negative breast cancer (TNBC) refers to an estrogen receptor negative, progesterone receptor negative, and HER2-negative breast cancer. Although accepted as a clinically valid category, TNBCs are heterogeneous at the histologic, immunohistochemical, and molecular levels. Gene expression profiling studies have molecularly classified TNBCs into multiple groups, but the prognostic significance is unclear except for a relatively good prognosis for the luminal androgen receptor (LAR) subtype. Immunohistochemistry (IHC) has been used as a surrogate for basal and luminal subtypes within TNBC, but prognostication of TNBC using IHC is not routinely performed. We aimed to study immunophenotypic correlations in a well-annotated cohort of consecutive TNBCs, excluding post-neoadjuvant chemotherapy cases. Tissue microarrays were constructed from a total of 245 TNBC cases. IHC stains were performed and consisted of luminal (AR, INPP4B), basal (SOX10, Nestin, CK5, EGFR), and diagnostic (GCDFP15, mammaglobin, GATA3, TRPS1) markers. Survival analysis was performed to assess the significance of clinical pathologic variables including age, histology, grade, lymphovascular invasion [LVI], Nottingham prognostic index [NPI] category, AJCC stage, stromal tumor-infiltrating lymphocytes at 10% increment, CD8+ T-cell count, Ki-67 index, PD-L1 status, and chemotherapy along with the results of IHC markers. Apocrine tumors show prominent reactivity for luminal markers and GCDFP15 while no special type carcinomas are often positive for basal markers. TRPS1 is a sensitive marker of breast carcinoma but shows low or no expression in apocrine tumors. High AJCC stage, lack of chemotherapy, and dual SOX10/AR negativity are associated with worse outcomes on univariable as well as multivariable analysis. LVI and higher NPI category were associated with worse outcomes on univariable but not multivariable analysis. The staining for IHC markers varies based on tumor histology which may be considered in determining breast origin. Notably, we report that SOX10/AR dual negative status in TNBC is associated with a worse prognosis along with AJCC stage, and chemotherapy status.

Genetics and Genomics of Pulmonary Fibrosis: Charting the Molecular Landscape and Shaping Precision Medicine.

Recent genetic and genomic advancements have elucidated the complex etiology of idiopathic pulmonary fibrosis (IPF) and other progressive fibrotic interstitial lung diseases (ILDs), emphasizing the contribution of heritable factors. This state-of-the-art review synthesizes evidence on significant genetic contributors to pulmonary fibrosis (PF), including rare genetic variants and common single nucleotide polymorphisms (SNPs). The MUC5B promoter variant is unusual, a common SNP that markedly elevates the risk of early and established PF. We address the utility of genetic variation in enhancing understanding of disease pathogenesis, clinical phenotypes, improving disease definitions, and informing prognosis and treatment response. Critical research gaps are highlighted, particularly the underrepresentation of non-European ancestries in PF genetic studies and the exploration of PF phenotypes beyond usual interstitial pneumonia (UIP)/IPF. We discuss the role of telomere length, often critically short in PF, and its link to progression and mortality, underscoring the genetic complexity involving telomere biology genes (TERT, TERC) and others like SFTPC and MUC5B. Additionally, we address the potential of gene-by-environment interactions to modulate disease manifestation, advocating for precision medicine in PF. Insights from gene expression profiling studies and multi-omic analyses highlight the promise for understanding disease pathogenesis and offer new approaches to clinical care, therapeutic drug development, and biomarker discovery. Finally, we discuss the ethical, legal, and social implications of genomic research and therapies in PF, stressing the need for sound practices and informed clinical genetic discussions. Looking forward, we advocate for comprehensive genetic testing panels and polygenic risk scores to improve the management of PF and related ILDs across diverse populations.

Invasive papillary carcinoma of the breast.

Invasive papillary carcinoma is a rare form of breast cancer that is more likely to occur in postmenopausal women. Previous studies have been limited to case reports and small retrospective studies, leading to low awareness of this type of tumor and difficult clinical management. According to the available literature, invasive papillary carcinoma exhibits unique pathological features and biological behaviors. Invasive papillary carcinoma is mostly luminal type, with a low rate of lymph node metastasis, which underlies its favorable prognosis. The effectiveness of adjuvant therapy in reducing tumor burden and improving prognosis in patients with invasive papillary carcinoma remains uncertain. Due to the rarity of the lesion, conducting prospective clinical trials is impractical. The use of biological models, such as organoids, can help alleviate the impact of the scarcity of this condition on research. In addition, invasive papillary carcinoma is affected by specific genomic events, and more extensive studies of gene expression profiling may provide molecular-level insights to make optimal therapeutic decisions.

Germline defects of familial hemophagocytic lymphohistiocytosis-related genes presenting as adult-onset peripheral T-cell lymphoma.

Germline mutations in genes involved in perforin-granzyme-mediated cytotoxicity such as PRF1, UNC13D, STX11, and STXBP2 were known to cause familial hemophagocytic lymphohistiocytosis (FHL). In this study, we reported a unique group of 3 patients with germline mutations of UNC13D and STX11 genes and presented as adult-onset peripheral T-cell lymphoma (PTCL) with cytotoxic T-cell phenotype and atypical lymphoma presentations. CD107a degranulation assay and NK-cell activity analysis demonstrated impaired cytotoxic function of the NK/T-cells of the patients with FHL-related mutations. Gene expression profile study revealed that up-regulated genes of the cytotoxic T-cells were enriched in autoimmune-related pathways. It was possible that impaired cytotoxic lymphocyte-mediated immune surveillance and autoantigen stimulation may both participate in PTCL oncogenesis. Germline defects of FLH-related genes may represent a novel predisposing factor for PTCLs.

Multi-contrast learning-guided lightweight few-shot learning scheme for predicting breast cancer molecular subtypes.

Invasive gene expression profiling studies have exposed prognostically significant breast cancer subtypes: normal-like, luminal, HER-2 enriched, and basal-like, which is defined in large part by human epidermal growth factor receptor 2 (HER-2), progesterone receptor (PR), and estrogen receptor (ER). However, while dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been generally employed in the screening and therapy of breast cancer, there is a challenging problem to noninvasively predict breast cancer molecular subtypes, which have extremely low-data regimes. In this paper, a novel few-shot learning scheme, which combines lightweight contrastive convolutional neural network (LC-CNN) and multi-contrast learning strategy (MCLS), is worthwhile to be developed for predicting molecular subtype of breast cancer in DCE-MRI. Moreover, MCLS is designed to construct One-vs-Rest and One-vs-One classification tasks, which addresses inter-class similarity among normal-like, luminal, HER-2 enriched, and basal-like. Extensive experiments demonstrate the superiority of our proposed scheme over state-of-the-art methods. Furthermore, our scheme is able to achieve competitive results on few samples due to joint LC-CNN and MCLS for excavating contrastive correlations of a pair of DCE-MRI.

Abstract WP318: Increased Synapse Elimination by Inflammatory Cells Contribute to Lon-Lasting Post-Stroke Memory Dysfunction in Aged Mice

Background and Purpose: Memory impairments are common after stroke. Memory dysfunction lasted longer in aged than in young mice, but the mechanisms are still unclear. Microglia maintain normal memory via removing excessive synapses and increase turnover of synaptic connections after stroke. Long-term memory deficits in aged mice may be associated with increased microglia in the brain. Hypothesis: Increased synapse removal by inflammatory cells contribute to the long-lasting post-stroke memory dysfunction of aged mice. Methods: Permanent distal middle cerebral artery occlusion (pMCAO) was induced in young and aged mice. The memory functions were analyzed weekly for 8 weeks by Y-maze test and at 8 weeks post stroke by novel objective recognition (NOR) test. Brain samples were collected 8 weeks after pMCAO induction. RNAseq analysis was performed to study gene expression profiles in peri-infarct area and hippocampus. Nissl staining was used to measure infarct volume and immunostaining was done to detect CD68 + and GFAP + cells and synapse in peri-infarct region and hippocampus. Results: RNAseq data shown up-regulation of CD68, GFAP, pro-inflammatory cytokines, immune response, microglia chemotaxins and phagocytosis genes; and down-regulation of synaptic assembly and transmission, synaptic plasticity, and long-term potentiation genes in aged mice at peri-infarct region and ipsilateral hippocampi. Aged mice had larger infarct volumes, more CD68 + and GFAP + cells in the peri-infarct region and ipsilateral hippocampi than young mice and had more CD68 + cells in the ipsilateral than the contralateral hippocampi. In Y-maze test, aged stroke mice made fewer spontaneous alternations from 3 to 8 weeks after pMCAO than young stroke and sham operated aged mice. In the NOR test, aged stroke mice spent less time on the novel objects than young stroke and sham aged mice. Increased synaptophysin positive CD68 + cells were detected in the hippocampi of aged stroke mice. Conclusions: Increase of synaptic elements by inflammatory cells contribute to the long-lasting post-stroke memory deficit in the aged mice, and reduction of neuroinflammation may improve their memory function.

Sequential gene expression analysis of myelodysplastic syndrome transformation identifies HOXB3 and HOXB7 as the novel targets for mesenchymal cells in disease

BackgroundMyelodysplastic syndrome (MDS) is known to arise through the pathogenic bone marrow mesenchymal stem cells (MSC) by interacting with hematopoietic stem cells (HSC). However, due to the strong heterogeneity of MDS patients, it is difficult to find common targets in studies with limited sample sizes. This study aimed to describe sequential molecular changes and identify biomarkers in MSC of MDS transformation.MethodsMultidimensional data from three publicly available microarray and TCGA datasets were analyzed. MDS-MSC was further isolated and cultured in vitro to determine the potential diagnostic and prognostic value of the identified biomarkers.ResultsWe demonstrated that normal MSCs presented greater molecular homogeneity than MDS-MSC. Biological process (embryonic skeletal system morphogenesis and angiogenesis) and pathways (p53 and MAPK) were enriched according to the differential gene expression. Furthermore, we identified HOXB3 and HOXB7 as potential causative genes gradually upregulated during the normal-MDS-AML transition. Blocking the HOXB3 and HOXB7 in MSCs could enhance the cell proliferation and differentiation, inhibit cell apoptosis and restore the function that supports hematopoietic differentiation in HSCs.ConclusionOur comprehensive study of gene expression profiling has identified dysregulated genes and biological processes in MSCs during MDS. HOXB3 and HOXB7 are proposed as novel surrogate targets for therapeutic and diagnostic applications in MDS.

Coexisting Th1 and Th2 cytokines in patients with collagenous gastritis and implications for its pathogenesis.

Collagenous gastritis (CG) is a rare cause of refractory dyspepsia and anemia that frequently affects children and young adults and whose histological hallmark is chronic mucosal inflammation with a subepithelial collagen band. The etiology remains obscure, and no established treatments exist. We investigated the pathogenesis of CG by determining the expression profiles of genes related to immunity and inflammation in index biopsies. Gastric biopsies from 10 newly diagnosed patients with CG were evaluated using the NanoString nCounter assay. Gastric biopsies from 14 normal individuals served as controls. The gene expression ratios for CG versus controls were determined in pooled samples and confirmed in individual samples by quantitative reverse transcription polymerase chain reaction. The results were compared with previously reported expression data from a cohort of patients with collagenous colitis, a colonic disorder with similar morphology, including subepithelial collagen band. CG biopsies featured enhanced expression of key genes encoding both Th1 (IFNγ, TNF-α, IL-2, IL-10, IL-12A, IL-12B, and IL-18) and Th2 cytokines (IL-3, IL-4, IL-5, IL-6, and IL-13). In contrast, biopsies from patients with CC exhibited upregulated Th1 cytokines only. We show in this first published gene expression profiling study that CG involves simultaneous upregulation of Th1 and Th2 cytokines. This finding is unique, contrasting with other types of chronic gastritis as well as with collagenous colitis, which shares the presence of a collagen band. Involvement of Th2 immunity in CG would support further investigation of potential dietary, environmental, or allergic factors to guide future therapeutic trials.

Neural Wiskott-Aldrich syndrome protein (N-WASP) promotes distant metastasis in pancreatic ductal adenocarcinoma via activation of LOXL2.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid malignancies. A specific mechanism of its metastasis has not been established. In this study, we investigated whether Neural Wiskott-Aldrich syndrome protein (N-WASP) plays a role in distant metastasis of PDAC. We found that N-WASP is markedly expressed in clinical patients with PDAC. Clinical analysis showed a notably more distant metastatic pattern in the N-WASP-high group compared to the N-WASP-low group. N-WASP was noted to be a novel mediator of epithelial-mesenchymal transition (EMT) via gene expression profile studies. Knockdown of N-WASP in pancreatic cancer cells significantly inhibited cell invasion, migration, and EMT. We also observed positive association of lysyl oxidase-like 2 (LOXL2) and focal adhesion kinase (FAK) with the N-WASP-mediated response, wherein EMT and invadopodia function were modulated. Both N-WASP and LOXL2 depletion significantly reduced the incidence of liver and lung metastatic lesions in orthotopic mouse models of pancreatic cancer. These results elucidate a novel role for N-WASP signaling associated with LOXL2 in EMT and invadopodia function, with respect to regulation of intercellular communication in tumor cells for promoting pancreatic cancer metastasis. These findings may aid in the development of therapeutic strategies against pancreatic cancer.

Identification of prognostic markers and potential therapeutic targets using gene expression profiling and simulation studies in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) has a 5-year relative survival rate of less than 10% making it one of the most fatal cancers. A lack of early measures of prognosis, challenges in molecular targeted therapy, ineffective adjuvant chemotherapy, and strong resistance to chemotherapy cumulatively make pancreatic cancer challenging to manage. The present study aims to enhance understanding of the disease mechanism and its progression by identifying prognostic biomarkers, potential drug targets, and candidate drugs that can be used for therapy in pancreatic cancer. Gene expression profiles from the GEO database were analyzed to identify reliable prognostic markers and potential drug targets. The disease's molecular mechanism and biological pathways were studied by investigating gene ontologies, KEGG pathways, and survival analysis to understand the strong prognostic power of key DEGs. FDA-approved anti-cancer drugs were screened through cell line databases, and docking studies were performed to identify drugs with high affinity for ARNTL2 and PIK3C2A. Molecular dynamic simulations of drug targets ARNTL2 and PIK3C2A in their native state and complex with nilotinib were carried out for 100 ns to validate their therapeutic potential in PDAC. Differentially expressed genes that are crucial regulators, including SUN1, PSMG3, PIK3C2A, SCRN1, and TRIAP1, were identified. Nilotinib as a candidate drug was screened using sensitivity analysis on CCLE and GDSC pancreatic cancer cell lines. Molecular dynamics simulations revealed the underlying mechanism of the binding of nilotinib with ARNTL2 and PIK3C2A and the dynamic perturbations. It validated nilotinib as a promising drug for pancreatic cancer. This study accounts for prognostic markers, drug targets, and repurposed anti-cancer drugs to highlight their usefulness for translational research on developing novel therapies. Our results revealed potential and prospective clinical applications in drug targets ARNTL2, EGFR, and PI3KC2A for pancreatic cancer therapy.

Inferred Gene Expression By Cell-Free DNA Profiling Allows Noninvasive Lymphoma Classification

Background : Current diagnostic criteria for mature B-cell tumors require a combination of histopathological, immunophenotypic, cytogenetic, and genetic evaluations on tissue biopsy specimens (Campo, Blood 2022; Alaggio, Leuk 2022). Despite this battery of techniques, substantial heterogeneity remains in specific subgroups that can be further resolved using additional molecular diagnostic methods, including gene expression profiling (GEP). For example, among aggressive B-cell tumors, a subset recognized as high-grade B-cell lymphomas can be identified as harboring MYC+BCL2 lesions by FISH (HGBCL-DH-BCL2). However, a significant remaining high-risk subset also have a characteristic tumor gene expression “double-hit signature” or “dark zone signature” (DZsig) (Ennishi, JCO 2018; Alduaij, Blood 2023). Yet, inadequate tissue specimens can limit the application of these techniques for some patients. Separately, the invasive nature of tissue biopsies and their attendant risks can preclude adequate diagnostic evaluations in some patients, and logistical barriers for obtaining surgical tissue specimens can result in diagnostic delays. To address these unmet needs, we tested the performance of a novel noninvasive strategy to detect and classify mature B-cell tumors using plasma cfDNA, with special attention to HGBCL-DH-BCL2 and DZsig. Methods : We used EPIC-Seq to infer expression levels for genes of interest, using cfDNA fragmentomic signals at their transcription start sites (Esfahani, Nat Biotech 2022). We first curated and catalogued genes from prior GEP studies (n=56) of >10k diverse lymphoid tumors profiled by various RNA techniques. We systematically prioritized genes recurrently identified in multiple studies of tumor-specific expression profiles as compared with other tumor types and normal tissues. We included canonical markers used for immunodiagnosis by IHC and FACS, as well as key lineage and differentiation markers of normal B and T cells, and other leukocyte subsets. Finally, we also included recurrently mutated genomic regions and fusion hotspots for quantifying ctDNA levels using variant allelic fractions (VAF). To validate performance of DZsig in FFPE for HGBCL-DH-BCL2, we analyzed 95 FFPE biopsies by FISH (20% HGBCL-DH-BCL2), IHC, and RNA-seq. We then analyzed 36 corresponding pretreatment cfDNA samples (28% HGBCL-DH-BCL2) and used EPIC-Seq to infer gene expression. Results: Starting from our curated catalogue, we designed a targeted lymphoid EPIC-Seq panel (1676 genes; 2.6 MB) to resolve 11 major mature lymphoid malignancies and their clinically relevant molecular subtypes (cHL, DLBCL, HGBCL, FL, MCL, BL, MZL, PMBCL, SLL/CLL, PTCL, and MM). We next applied this EPIC-Seq panel to profile cfDNA samples from 207 lymphoma patients, including cHL (n=113), DLBCL (n=66), FL (n=15), and MCL (n=13) as well as healthy adults to assess specificity. We tested histology specific signatures derived from several existing RNA GEP datasets for cHL from sorted HRS cells (~85k by scRNA-Seq) and for DLBCL (n=959), FL (n=635), and MCL (n=100) from bulk RNA-Seq. Using this approach, we found high correlations between EPIC-Seq signature scores from cfDNA and corresponding circulating tumor VAFs in each histology [cHL (R p=0.83), DLBCL (R p=0.83), FL (R p=0.87), MCL (R p=0.81); Fig A]. In addition, when measuring these tumor derived signatures in cfDNA, each histology was significantly distinguishable from healthy controls (AUCs: cHL 0.94, DLBCL 0.91, FL 0.77, MCL 0.96). We next evaluated the DZsig when measured in LBCL patients and comparing paired tumor and cfDNA samples. We first confirmed the performance of the DZsig for detection of HGBCL-DH-BCL2 in 95 FFPE tumors by RNA-Seq (p<0.0001, AUC 0.85). We then noninvasively measured the DZsig in plasma cfDNA by EPIC-Seq (cfDZsig) and found significant discrimination of HGBCL-DH-BCL2 and DLBCL (p=0.0088, AUC 0.78, Fig B). Conclusions: These results confirm that inferred gene expression by cfDNA profiling allows noninvasive diagnosis of multiple lymphoma subtypes, including classification of challenging diagnostic entities such as HGBCL and DZsig+ tumors. Our ability to design and validate a pan-lymphoid gene panel for detection and classification of several lymphoma subtypes suggests the promise of this approach for other diverse tumors as well as the refinement of cfDZsig using a larger cohort.

Transcriptome Profiling Data of Tea Leaves During Infection by the Dark Brown Tea Leaf Spot Pathogen Epicoccum mackenziei

Dark brown leaf spot on tea ( Camellia sinensis (L.) O. Kuntze) caused by Epicoccum mackenziei Jayasiri, Camporesi & K. D. Hyde has caused a loss in the yield and quality of tea leaves in Guizhou Province, Southwest China. No research has been published on the gene expression profiles of tea leaves during infection by E. mackenziei. In this study, we report the high-quality transcriptome sequencing of tea genes during infection, using high-throughput next-generation sequencing on the Illumina Novaseq 6000 platform. The infection resulted in significantly up- or downregulated expression of the 960 or 397 differentially expressed mRNAs (DEmRNAs) from tea leaves, respectively. The DEmRNAs were annotated using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. The expression of DEmRNA peroxidase 21 (TEA000222.1) was upregulated in response to infection by the pathogen and was enriched in terms of defense response to fungi at the biological process aspect. Expression of 26 or 13 of the tea DEmRNAs enriched in the pathways of plant-pathogen interaction were up- or downregulated, respectively, such as the genes WRKY transcription factor 1 (TEA028099.1), probable disease resistance protein At4g27220 (TEA018574.1), and serine/threonine-protein kinase CDL1 (TEA006388.1), which were downregulated. This comprehensive gene expression profiling study of tea leaves infected by this fungal pathogen will provide a valuable resource for future research on the identification of the host genes associated with the response to pathogen challenge and ultimately with disease resistance in the host. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

Effect of labor pain on placental gene expressions

A close relationship between labor and the placenta is known. The study of gene expression profiles describing the effects of labor on placental tissue has accelerated in recent years. This study aims to compare the expression levels of GDF15, ADM, SERPINE1, NOS3, IL 6, TNF-α genes in placental tissues discarded after vaginal deliveries with labor pain and elective cesarean deliveries before the onset of labor pain. For this purpose, placental tissues of vaginal deliveries with labor pain (n=9) and elective cesarean deliveries without labor pain (n=9) were collected immediately after births. RNA extracted from tissues (umblical cords and deciduas). Gene expression analyzes were performed by Real-time PCR method. TNF-α gene expression levels in decidua and umblical cord tissues in vaginal deliveries with labor pain were higher than in elective cesareans without labor pain, and NOS3, ADM, SERPINE1 gene expression levels were low. GDF15 and IL-6 gene expression levels were high in the umblical cord tissues and were low in the decidua in vaginal deliveries with labor pain compared to elective cesareans without labor pain. The high level of GDF15 gene expression in the vaginal deliveries with labor pain umblical cord tissues was significant (p<0.05). Changes in gene expression between different types of birth may help us to understand how labor pain affects gene expression levels. These results suggest that labor pain affects different tissues in different ways. The “birth experience” of a placenta that has experienced pain stress is absolutely different to others process. Since birth pain is a natural stress, it can be a light in determining the effects of the differences in cesarean section on the baby and the mother. Gene expression alterations may cause labor starting and progressing, or just be an result of labor.

Lenalidomide and Carfilzomib in Relapsed and Refractory T Follicular Helper Lymphomas

Lenalidomide and Carfilzomib in Relapsed and Refractory T Follicular Helper Lymphomas

JAAD Game Changer: “Primary dermal melanoma: A unique subtype of melanoma to be distinguished from cutaneous metastatic melanoma: A clinical, histologic, and gene expression-profiling study”

JAAD Game Changer: “Primary dermal melanoma: A unique subtype of melanoma to be distinguished from cutaneous metastatic melanoma: A clinical, histologic, and gene expression-profiling study”

Transcriptomic and lipidomic profiling of subcutaneous and visceral adipose tissues in 15 vertebrates

The storage of lipids as energy in adipose tissue (AT) has been conserved over the course of evolution. However, substantial differences in ATs physiological activities were reported among species. Hence, establishing the mechanisms shaping evolutionarily divergence in ATs transcriptomes could provide a deeper understanding of AT regulation and its roles in obesity-related diseases. While previous studies performed anatomical, physiological and morphological comparisons between ATs across different species, little is currently understood at the molecular phenotypic levels. Here, we characterized transcriptional and lipidomic profiles of available subcutaneous and visceral ATs samples across 15 vertebrate species, spanning more than 300 million years of evolution, including placental mammals, birds and reptiles. We provide detailed descriptions of the datasets produced in this study and report gene expression and lipid profiles across samples. We demonstrate these data are robust and reveal the AT transcriptome and lipidome vary greater among species than within the same species. These datasets may serve as a resource for future studies on the functional differences among ATs in vertebrate species.

Personalized medicine in sarcoidosis: unravelling biomarkers for targeted care.

This review provides an assessment of biomarkers in sarcoidosis, aiming to address the need for improved diagnostic, prognostic and management tools. Sarcoidosis presents diagnostic challenges, necessitating the search for reliable biomarkers to guide clinical decisions. Established biomarkers such as serum angiotensin-converting enzyme (ACE) and serum interleukin-2 receptor (sIL-2R) have limitations in sensitivity and specificity. FDG-PET/CT imaging shows promising results in assessing disease activity and guiding immunosuppression. Gene expression profiling studies reveal potential biomarkers, particularly involving TH1 immune response and IFN-γ-driven signalling pathways. The field of omics sciences offers opportunities for novel biomarker discovery. These findings have implications for clinical practice and research. The limitations of established biomarkers underscore the need for improved diagnostic tools in sarcoidosis. The potential of FDG-PET/CT imaging requires further exploration. Gene expression profiling and omics sciences offer avenues for discovering novel biomarkers to enhance diagnosis and predict disease progression. Such advancements can facilitate personalized treatment strategies and improve patient outcomes. Continued research is vital to validate the efficacy and clinical applicability of these biomarkers. Overall, this review emphasizes ongoing efforts to advance sarcoidosis biomarkers research and improve disease management.

Fixation and Laser Capture Microdissection of Plant Tissue for RNA Extraction and RNASeq Library Preparation.

To study the transcriptome of individual plant cells at specific points in time, we developed protocols for fixation, embedding, and sectioning of plant tissue followed by laser capture microdissection (LCM) and processing for RNA recovery. LCM allows the isolation of individual cell types from heterogeneous tissue sections and is particularly suited to plant processing because it does not require the breakdown of cell walls. This approach allows accurate separation of a small volume of cells that can be used to study gene expression profiles in different tissues or cell layers. The technique requires neither separation of cells by enzymatic digestion of any kind nor cell-specific reporter genes, and it allows storage of fixed and embedded tissue for months before capture. The methods for fixation, embedding, sectioning, and capturing of plant cells that we describe yield high-quality RNA suitable for making libraries for RNASeq. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Tissue Preparation for Laser Capture Microdissection Basic Protocol 2: Tissue Sectioning Basic Protocol 3: Laser Capture Microdissection of Embedded Tissue Basic Protocol 4: RNA Extraction from Laser Capture Microdissection Samples.

Identification of lncRNAs Deregulated in Epithelial Ovarian Cancer Based on a Gene Expression Profiling Meta-Analysis.

Epithelial ovarian cancer (EOC) is one of the deadliest gynecological cancers worldwide, mainly because of its initially asymptomatic nature and consequently late diagnosis. Long non-coding RNAs (lncRNA) are non-coding transcripts of more than 200 nucleotides, whose deregulation is involved in pathologies such as EOC, and are therefore envisaged as future biomarkers. We present a meta-analysis of available gene expression profiling (microarray and RNA sequencing) studies from EOC patients to identify lncRNA genes with diagnostic and prognostic value. In this meta-analysis, we include 46 independent cohorts, along with available expression profiling data from EOC cell lines. Differential expression analyses were conducted to identify those lncRNAs that are deregulated in (i) EOC versus healthy ovary tissue, (ii) unfavorable versus more favorable prognosis, (iii) metastatic versus primary tumors, (iv) chemoresistant versus chemosensitive EOC, and (v) correlation to specific histological subtypes of EOC. From the results of this meta-analysis, we established a panel of lncRNAs that are highly correlated with EOC. The panel includes several lncRNAs that are already known and even functionally characterized in EOC, but also lncRNAs that have not been previously correlated with this cancer, and which are discussed in relation to their putative role in EOC and their potential use as clinically relevant tools.