Intratumoral microbiome
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB47824 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Copy number analyses of regionally separated intratumoral biopsies of prostate cancers. Intratumoral heterogeneity (ITH) leads to regional biases of the mutational landscape in a single tumor and may influence the single biopsy-based clinical diagnosis and treatment decision. To evaluate the extent of ITH in unifocal prostate cancers (PCAs) that had not been sought, we analyzed multiple regional biopsies from three PCAs using DNA copy number analyses. DNA copy number showed ITH including regional biases in the presentation of a well-known driver of TMPRSS2-ERG fusion. Our analyses identified a substantial level of genetic ITH in unifocal PCAs at the genomic levels, which should be taken into account for the curation of biomarkers in the clinical setting. Four intratumoral biopsies were obtained per tumor for three prostate cancers. Radical prostatectomy tissue from three patients with prostate cancers were obtained. Board-certified pathologists reviewed the hematoxylin&eosin stained sections and identified tumor-rich regions (> 80% purity). We selected four different areas for biopsy that were at least 5mm apart and were comprised of the most common Gleason pattern (the most common histologic patterns with minimal histologic differences). Copy number profiling was performed using Agilent 180K platform according to the manufacturer's protocol.
2014-01-18 | E-GEOD-54185 | biostudies-arrayexpress
Project description:Small cell lung cancer (SCLC) is an aggressive malignancy characterized by rapid onset of resistance to platinum chemotherapy. However, the mechanisms underlying platinum-resistance remain obscure in part due to scarcity of tissue samples, particularly from relapsed patients. Here, we generated circulating tumor cell (CTC)-derived xenograft (CDX) models from SCLC patients before or after relapse that faithfully recapitulate patient tumor genomics and platinum response. Platinum-sensitive models were relatively homogeneous, whereas transcriptomic and proteomic analyses revealed enrichment of multiple targetable pathways and intertumoral heterogeneity among resistant models. Single-cell RNAseq profiling further identified greater intratumoral heterogeneity (ITH) associated with platinum-resistance. This included a population of DLL3low cells in resistant CDX models that demonstrated greater chemoresistance, suggesting that subtle shifts in the proportion of DLL3-expressing cells could impact response. Similarly, longitudinal single-cell transcriptional profiling of CTCs from patient blood reveals emergence of molecular markers of resistance and significantly greater ITH after disease relapse. Together, these data suggest that platinum-resistance involves a heterogeneous process of transcriptional fluidity with contributions from both preexisting cellular subpopulations and outgrowth of resistant populations, yielding a diverse cellular composition refractory to single-agent therapeutics.
2020-02-12 | GSE138418 | GEO
Project description:The aim of this study was to investigate the effect of VEGF targeted therapy (sunitinib) on intratumoral heterogeneity (ITH) in metastatic clear cell renal cancer (mRCC). 138 samples from patients with clear cell renal cell carcinoma, including biological replicates of nephrectomy samples. RNA extracted fresh frozen tissue samples.
2015-05-25 | E-GEOD-65615 | biostudies-arrayexpress
Project description:Intratumoral Transcriptional States of Lymphoma
| PRJNA389979 | ENA
Project description:Acquired drug resistance is the major therapeutic obstacle to maintenance treatment of advanced-stage non-small cell lung cancer. Lung adenocarcinoma (ADC) harboring driver mutations also showed poor response to immune checkpoint inhibitors (ICIs). Underlying mechanisms of how drug insensitivity evolves remain unclear. Here we explored the intratumoral heterogeneity of tyrosine kinase inhibitor (TKI)-resistant anaplastic lymphoma kinase (ALK)-rearranged lung ADC organoids using single-cell RNA-sequencing (scRNA-seq) transcriptomic analysis. IL-17 signaling pathway was found highly induced in a subpopulation of pre-existing ALK-TKI-resistant cells. These drug-tolerant persister (DTP) cells, also found to have high surface intracellular adhesion molecule 1 (ICAM-1) expression level, were more resistant towards ALK-TKI and expressed a higher level of cancer-stem cell transcriptional factors. Moreover, tumor cells with high ICAM-1 expression were found spatially correlated with RORɣt+ Th17 infiltration in ALK-rearranged NSCLC resected tumor tissues. In conclusion, our data revealed marked intratumoral heterogeneity in ALK-rearranged tumor, and pre-existing DTP cells may contribute to the development of drug insensitivity in ALK-rearranged lung ADC.
2023-08-09 | GSE223779 | GEO
Project description:Chemotherapeutic remodeling of the gut microbiome
| PRJEB26424 | ENA
Project description:To determine the effect on gene expression of intratumoral injection of the Toll-like receptor agonist CpG1826. MC38 colon cancer cells were injected subcutaneously into C57BL/6 mice and allowed to establish until ~40 mm2.
2009-09-23 | GSE18203 | GEO
Project description:Vaginal microbiome composition drives metabolic profiles in healthy pregnancy
| PRJEB33234 | ENA
Project description:Significant gut microbiota heterogeneity exists amongst UC patients though the clinical implications of this variance are unknown. European and South Asian UC patients exhibit distinct disease risk alleles, many of which regulate immune function and relate to variation in gut microbiota β-diversity. We hypothesized ethnically distinct UC patients exhibit discrete gut microbiotas with unique luminal metabolic programming that influence adaptive immune responses and relate to clinical status. Using parallel bacterial 16S rRNA and fungal ITS2 sequencing of fecal samples (UC n=30; healthy n=13), we corroborated previous observations of UC-associated depletion of bacterial diversity and demonstrated significant gastrointestinal expansion of Saccharomycetales as a novel UC characteristic. We identified four distinct microbial community states (MCS 1-4), confirmed their existence using microbiota data from an independent UC cohort, and show they co-associate with patient ethnicity and degree of disease severity. Each MCS was predicted to be uniquely enriched for specific amino acid, carbohydrate, and lipid metabolism pathways and exhibited significant luminal enrichment of metabolic products from these pathways. Using a novel in vitro human DC/T-cell assay we show that DC exposure to patient fecal water led to MCS -specific changes in T-cell populations, particularly the Th1:Th2 ratio, and that patients with the most severe disease exhibited the greatest Th2 skewing. Thus, based on ethnicity, microbiome composition, and associated metabolic dysfunction, UC patients may be stratified in a clinically and immunologically meaningful manner, providing a platform for the development of FMC-focused therapy. Fecal microbiome was assessed with Affymetrix PhyloChip arrays from patients with ulcerative colitis and healthy controls.
2016-07-25 | E-GEOD-78724 | biostudies-arrayexpress