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PROVIDER: PRJNA342007 | ENA |
REPOSITORIES: ENA
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Project description:INTRODUCTION. Liquid biopsies are a minimally invasive collection of a patient body fluid sample. In oncology, they offer several advantages compared to traditional tissue biopsies. However, potential of this method in endometrial cancer (EC) remains poorly explored. We studied the utility of tumor educated platelets (TEPs) and circulating tumor DNA (ctDNA) for preoperative EC diagnosis, including histology determination. MATERIALS AND METHODS. TEPs from 297 subjects (53 EC patients, 40 patients with benign gynecologic conditions and 204 healthy women) were RNA-sequenced. DNA sequencing was performed in 519 primary tumor tissue samples and in16 plasma samples. Artificial intelligence was applied to sample classification. RESULTS. Platelet-dedicated classifier yielded AUC of 93.1% in test set when discriminating between healthy subjects and cancer patients. However, the discrimination between endometrial cancer and benign gynecologic conditions was relatively low, with AUC of 60.7%. ctDNA-dedicated classifier discriminated primary tumor tissue samples with AUC of 91.4% and ctDNA blood samples with AUC of 87.5%. CONCLUSIONS Liquid biopsies show potential in EC diagnosis. Both TEPs and ctDNA profiles coupled with artificial intelligence constitute a source of useful information. Further work, involving more cases, is warranted.
2021-12-01 | GSE184904 | GEO
Project description:Circulating tumor DNA (ctDNA) as a biomarker of disease activity in classic Hodgkin lymphoma (cHL) patients are still not well-defined. By profiling primary tumors and ctDNA, we identified common variants between primary tumors and longitudinal plasma samples in most of the cases, confirming high PBatial and temporal heterogeneity. Though ctDNA analyses mirrored HRS cell genetics overall, the prevalence of variants shows that none of them can be used as a single biomarker. Conversely, the estimation of hGE/mL, based in total ctDNA quantification, reflects disease activity and is almost perfectly correlated with standard parameters such as PET/CT that are associated with refractoriness.
2023-12-18 | GSE244989 | GEO
Project description:Introduction: microRNAs are promising candidate breast cancer biomarkers due to their cancer-specific expression profiles. However, efforts to develop circulating breast cancer biomarkers are challenged by the heterogeneity of microRNAs in the blood. To overcome this challenge, we aimed to develop a molecular profile of microRNAs specifically secreted from breast cancer cells. Our first step towards this direction relates to capturing and analyzing the contents of exosomes, which are small secretory vesicles that selectively encapsulate microRNAs indicative of their cell of origin. To our knowledge, circulating exosome microRNAs have not been well evaluated as biomarkers for breast cancer diagnosis or monitoring. Methods: Exosomes were collected from the conditioned media of human breast cancer cell lines, mouse plasma of patient-derived orthotopic xenograft models (PDX), and human plasma samples. Exosomes were verified by electron microscopy, nanoparticle tracking analysis, and western blot. Cellular and exosome microRNAs from breast cancer cell lines were profiled by next-generation small RNA sequencing. Plasma exosome microRNA expression was analyzed by qRT-PCR analysis. Results: Small RNA sequencing and qRT-PCR analysis showed that several microRNAs are selectively encapsulated or highly enriched in breast cancer exosomes. Importantly, the selectively enriched exosome microRNA, human miR-1246, was detected at significantly higher levels in exosomes isolated from PDX mouse plasma, indicating that tumor exosome microRNAs are released into the circulation and can serve as plasma biomarkers for breast cancer. This observation was extended to human plasma samples where miR-1246 and miR-21 were detected at significantly higher levels in the plasma exosomes of 16 breast cancer patients as compared to the plasma exosomes of healthy control subjects. Receiver Operating Characteristic (ROC) curve analysis indicated that the combination of plasma exosome miR-1246 and miR-21 levels is a better indicator of breast cancer than their individual levels. Conclusions: Our results demonstrate that certain microRNA species, such as miR-21 and miR-1246, are selectively enriched in human breast cancer exosomes and significantly elevated in the plasma of breast cancer patients. These findings indicate a potential new strategy to selectively analyze plasma breast cancer microRNAs indicative of the presence of breast cancer.
2016-09-12 | GSE83669 | GEO
Project description:Triple Negative Breast Cancer (TNBC) is an aggressive subtype of breast cancer with high intra-tumoral heterogeneity, frequently resistant to treatment and no known targeted therapy available to improve patient outcomes. It has been hypothesized that the genomic architecture of a TNBC tumour evolves over time, both before, and during therapy, leading to therapy resistance and a high propensity to relapse. Whether this is an inherent property of the tumour or acquired over time is not well characterized. Despite this important clinical implication, limited studies have been carried out to unravel temporal evolution of TNBC over time. Herein, we report an OMICS based analysis of three TNBC patients who were longitudinally sampled during their treatment at different times of relapse. We recruited three TNBC patients at the time of their first relapse who were then followed-up through the course of their treatment. We obtained retrospective samples (tumour samples) from patient tumours at diagnosis (before neo-adjuvant chemotherapy - NACT) at surgery (post NACT) and prospectively sampled them at each subsequent relapse (tumour, blood plasma, and buffy coat) as determined by RECIST criteria. Tumor and buffy coat DNA were subjected to whole exome sequencing (WES) at 200x, and SNP arrays for copy number variation (CNV) analysis. RNA from tumour samples at relapse was subjected to whole transcriptome sequencing. Pathogenic germline BRCA1 variants identified in WES were validated using Sanger sequencing. 1084 somatic mutations identified in whole exome sequencing of all tumour tissues (n=13) from three patients, were subjected to a custom amplicon ultra-deep sequencing assay at 30,000X in their germline DNA (n=3), tumour DNA (n=10), and cfDNA from plasma samples at relapse (n=8). Copy number corrected allele frequencies, tumour ploidy, tumour purity, and ultra-deep sequencing assay derived variant allele frequencies were used to infer clonal and phylogenetic architecture of each patient as it evolved under selective pressure of therapy over time. Clonality analysis incorporating allele fractions from ultra-deep sequencing identified clones comprising of mutations that are present throughout the course of therapy which we term as founding clones and stem mutations respectively. Such founding clones comprising of stem mutations in all 3 patients were present throughout the course of treatment, irrespective of change in treatment modalities. These stem clones included well characterized cancer related genes like PDGFRB & ARID2 (Patient 02), TP53, BRAF & CSF3R (Patient 04) and ESR1, APC, EZH2 & TP53 (Patient 07). Such branching evolution is seen in all three patients wherein the dominant clone (stem clone) acquires additional mutations to form sub-clones, while persisting over time. These sub-clones may be chemo and radio resistant, while also providing for organ specific metastatic potential. Allele fractions of expressed variants inferred from RNA-Seq data co-related with allele fractions from WES data indicating that all somatic.
2023-08-09 | E-MTAB-11379 | biostudies-arrayexpress
Project description:Triple Negative Breast Cancer (TNBC) is an aggressive subtype of breast cancer with high intra-tumoral heterogeneity, frequently resistant to treatment and no known targeted therapy available to improve patient outcomes. It has been hypothesized that the genomic architecture of a TNBC tumour evolves over time, both before, and during therapy, leading to therapy resistance and a high propensity to relapse. Whether this is an inherent property of the tumour or acquired over time is not well characterized. Despite this important clinical implication, limited studies have been carried out to unravel temporal evolution of TNBC over time. Herein, we report an OMICS based analysis of three TNBC patients who were longitudinally sampled during their treatment at different times of relapse. We recruited three TNBC patients at the time of their first relapse who were then followed-up through the course of their treatment. We obtained retrospective samples (tumour samples) from patient tumours at diagnosis (before neo-adjuvant chemotherapy - NACT) at surgery (post NACT) and prospectively sampled them at each subsequent relapse (tumour, blood plasma, and buffy coat) as determined by RECIST criteria. Tumor and buffy coat DNA were subjected to whole exome sequencing (WES) at 200x, and SNP arrays for copy number variation (CNV) analysis. RNA from tumour samples at relapse was subjected to whole transcriptome sequencing. Pathogenic germline BRCA1 variants identified in WES were validated using Sanger sequencing. 1084 somatic mutations identified in whole exome sequencing of all tumour tissues (n=13) from three patients, were subjected to a custom amplicon ultra-deep sequencing assay at 30,000X in their germline DNA (n=3), tumour DNA (n=10), and cfDNA from plasma samples at relapse (n=8). Copy number corrected allele frequencies, tumour ploidy, tumour purity, and ultra-deep sequencing assay derived variant allele frequencies were used to infer clonal and phylogenetic architecture of each patient as it evolved under selective pressure of therapy over time. Clonality analysis incorporating allele fractions from ultra-deep sequencing identified clones comprising of mutations that are present throughout the course of therapy which we term as founding clones and stem mutations respectively. Such founding clones comprising of stem mutations in all 3 patients were present throughout the course of treatment, irrespective of change in treatment modalities. These stem clones included well characterized cancer related genes like PDGFRB & ARID2 (Patient 02), TP53, BRAF & CSF3R (Patient 04) and ESR1, APC, EZH2 & TP53 (Patient 07). Such branching evolution is seen in all three patients wherein the dominant clone (stem clone) acquires additional mutations to form sub-clones, while persisting over time. These sub-clones may be chemo and radio resistant, while also providing for organ specific metastatic potential. Allele fractions of expressed variants inferred from RNA-Seq data co-related with allele fractions from WES data indicating that all somatic.
2023-08-18 | E-MTAB-11376 | biostudies-arrayexpress
Project description:Study investigating the role of miRNAs in breast cancer detection miRNA extracted from plasma on 20 breast cancer patients, 20 controls, 20 post-resection breast cancer patients and 10 lung/colorectal cancer patients, miRNA quanitification using Illumina microarray
2012-10-13 | E-GEOD-41526 | biostudies-arrayexpress
Project description:Breast cancer (BC) comprises multiple subtypes with distinct molecular features, which differ in their interplay with host immunity, prognosis, and treatment. The triple-negative and HER2(+) subtypes are generally more immunogenic and associated with better immunotherapy responsiveness than the luminal subtypes. Non-invasive blood analyses can provide valuable insights into systemic immunity during cancer. The aim of this study was to analyze the expression of transcriptional isoforms in peripheral blood mononuclear cells (PBMCs) from BC patients and healthy women to identify potential BC immune biomarkers. RNA-sequencing and isoform-level bioinformatics were performed on PBMCs from 13 triple-negative and 13 luminal A patients. Isoform expression validation by qRT-PCR and clinicopathological correlations were performed in a larger cohort (156 BC patients and 32 healthy women). Transcriptional analyses showed a significant (p<.001) decrease of the ENST00000374459 RASGEF1A isoform in PBMCs of BC compared to healthy subjects, indi-cating disease-related expression changes. The decrease was associated with higher ctDNA and Ki-67 values. The levels of the RASGEF1A transcriptional isoform ENST00000374459 may have the potential to distinguish between BC and healthy subjects. The downregulation of ENST00000374459 in breast cancer is associated with higher proliferation and ctDNA shedding. Specialized bioinformatics analyses such as isoform analyses hold significant promise in the detection of biomarkers, since variant-indiscriminate (standard) RNA sequencing analyses may overlook specific transcriptional changes that may be disease-associated and biologically important.
2024-09-13 | GSE270376 | GEO
Project description:Plasma small noncoding RNA levels were measured in breast cancer patients and healthy control women, to determine whether any of these were associated with either patient prognosis, or as diagnostic markers for breast cancer.
2019-08-31 | GSE118782 | GEO