Browse
Submit Data
Databases
API
Help

Dataset Information

19 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Longitudinal Monitoring of Plasma Circulating Tumour DNA Enables the Prediction of Early Relapse in Patients with Non-Hodgkin Lymphoma: A Case Series.

ABSTRACT: Growing evidence now suggests that circulating tumour DNA (ctDNA) has great potential as a non-invasive biomarker for disease monitoring, since ctDNA carries tumour-specific modifications. In particular, monitoring ctDNA has important implications for identifying patients with haematological malignancies at clinical risk of disease progression. We hereby describe three patients with B-cell non-Hodgkin lymphoma and investigate the clinical value of sequential ctDNA profiling for the early detection of tumour relapse. Somatic mutations in diagnostic tumour biopsy samples of these three patients were identified by applying high-throughput next-generation sequencing. Droplet digital PCR probes and primers were designed and tested for each hotspot mutation. Serial ctDNA analysis was subsequently conducted among these three patients. We found that the longitudinal monitoring of plasma ctDNA could predict for at least one month in advance compared with flow cytometry, cytology and conventional imaging modalities. Therefore, our results support liquid biopsy based on ctDNA as a non-invasive complementary modality to other detection methods for detecting early relapse and contribute to more precise management for non-Hodgkin lymphoma patients.

SUBMITTER: Ji H

PROVIDER: S-EPMC8618087 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Longitudinal monitoring of circulating tumour DNA improves prognostication and relapse detection in gastroesophageal adenocarcinoma.

Project description:BackgroundGastroesophageal adenocarcinoma (GOA) has poor clinical outcomes and lacks reliable blood markers. Here we present circulating tumour DNA (ctDNA) as an emerging biomarker.MethodsForty patients (17 palliative and 23 curative) were followed by serial plasma monitoring. Primary tumour DNA was analysed by targeted next-generation sequencing to identify somatic single-nucleotide variants (SNVs), and Nanostring nCounter® to detect copy number alterations (CNAs). Patient-specific SNVs and CNA amplifications (CNAamp) were analysed in plasma using digital droplet PCR and quantitative PCR, respectively.ResultsThirty-five patients (13 palliative, 22 curative) had ≥1 SNVs and/or CNAamp detected in primary tumour DNA suitable for tracking in plasma. Eighteen of 35 patients (nine palliative, nine curative) had ≥1 ctDNA-positive plasma sample. Detection of postoperative ctDNA predicted short RFS (190 vs 934 days, HR = 3.7, p = 0.028) and subsequent relapse (PPV for relapse 0.83). High ctDNA levels (>60.5 copies/ml) at diagnosis of metastatic disease predicted poor OS (90 vs 372 days, HR = 11.7 p < 0.001).ConclusionSensitive ctDNA detection allows disease monitoring and prediction of short OS in metastatic patients. Presence of ctDNA postoperatively predicts relapse and defines a 'molecular relapse' before overt clinical disease. This lead time defines a potential therapeutic window for additional anticancer therapy.

| S-EPMC7555811 | biostudies-literature

Plasma vesicle miRNAs for therapy response monitoring in Hodgkin lymphoma patients.

Project description:BACKGROUND. Cell-free circulating nucleic acids, including 22-nt microRNAs (miRNAs), represent noninvasive biomarkers for treatment response monitoring of cancer patients. While the majority of plasma miRNA is bound to proteins, a smaller, less well-characterized pool is associated with extracellular vesicles (EVs). Here, we addressed whether EV-associated miRNAs reflect metabolic disease in classical Hodgkin lymphoma (cHL) patients. METHODS. With standardized size-exclusion chromatography (SEC), we isolated EV-associated extracellular RNA (exRNA) fractions and protein-bound miRNA from plasma of cHL patients and healthy subjects. We performed a comprehensive small RNA sequencing analysis and validation by TaqMan qRT-PCR for candidate discovery. Fluorodeoxyglucose-PET (FDG-PET) status before treatment, directly after treatment, and during long-term follow-up was compared directly with EV miRNA levels. RESULTS. The plasma EV miRNA repertoire was more extensive compared with protein-bound miRNA that was heavily dominated by a few abundant miRNA species and was less informative of disease status. Purified EV fractions of untreated cHL patients and tumor EVs had enriched levels of miR24-3p, miR127-3p, miR21-5p, miR155-5p, and let7a-5p compared with EV fractions from healthy subjects and disease controls. Serial monitoring of EV miRNA levels in patients before treatment, directly after treatment, and during long-term follow-up revealed robust, stable decreases in miRNA levels matching a complete metabolic response, as observed with FDG-PET. Importantly, EV miRNA levels rose again in relapse patients. CONCLUSION. We conclude that cHL-related miRNA levels in circulating EVs reflect the presence of vital tumor tissue and are suitable for therapy response and relapse monitoring in individual cHL patients. FUNDING. Cancer Center Amsterdam Foundation (CCA-2013), Dutch Cancer Society (KWF-5510), Technology Foundation STW (STW Perspectief CANCER-ID).

| S-EPMC5111516 | biostudies-literature

Circulating tumor DNA for monitoring classic Hodgkin lymphoma patients: correlation with FDG-PET/CT

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

Targeted genotyping of circulating tumor DNA for classical Hodgkin lymphoma monitoring: a prospective study.

Project description:The relevance of circulating tumor DNA (ctDNA) analysis as a liquid biopsy and minimal residual disease tool in the management of classical Hodgkin Lymphoma (cHL) patients was demonstrated in retrospective settings and remains to be confirmed in a prospective setting. We developed a targeted Next-Generation sequencing (NGS) panel for fast analysis (AmpliSeq technology) of nine commonly mutated genes in biopies and ctDNA of cHL patients. We then conducted a prospective trial to assess ctDNA follow up at diagnosis and after 2 cycles of chemotherapy (C2). Sixty cHL patients treated by first line conventional chemotherapy (BEACOPPescalated [21.3%], ABVD/ABVD-like [73.5%] and other regimens [5.2%, for elderly patients] were assessed in this non-interventional study. Median age of the patients was 33.5 years (range 20-86). Variants were identified in 42 (70%) patients. Mutations of NFKBIE, TNFAIP3, STAT6, PTPN1, B2M, XPO1, ITPKB, GNA13 and SOCS1 were found in 13.3%, 31.7%, 23.3%, 5%, 33.3%, 10%, 23.3%, 13.3% and 50% of patients, respectively. ctDNA concentration and genotype are correlated with clinical characteristics and presentation. Regarding early therapeutic response, 45 patients (83%, NA=6) had a negative positron emission tomography (PET) after C2 (Deauville Score 1-3). Mean of DeltaSUVmax after C2 was -78.8%. We analyzed ctDNA after C2 for 54 patients (90%). ctDNA became rapidly undetectable in all cases after C2. Variant detection in ctDNA is suitable to depict the genetic features of cHL at diagnosis and may help to assess early treatment response, in association with PET. Clinical Trial reference: NCT02815137.

| S-EPMC7776248 | biostudies-literature

Multiloculated Cavitary Primary Pulmonary Hodgkin Lymphoma: Case Series.

Project description:Primary pulmonary Hodgkin lymphoma (PPHL) is very rare and typically involves the superior portion of the lung. Pulmonary involvement is observed in 15-40% of Hodgkin lymphoma patients. Three such patients who presented with an unusual form of PPHL in radiological studies, i.e., multiloculated cavitary lesions, were admitted to our hospital. These lesions represent a new pathological and radiological feature of PPHL.

| S-EPMC5869374 | biostudies-other

Circulating clonotypic B cells in classic Hodgkin lymphoma.

Project description:Although Hodgkin and Reed-Sternberg (HRS) cells are B lymphoid cells, they are unlike any normal cells of that lineage. Moreover, the limited proliferative potential of HRS cells belies the clinical aggressiveness of Hodgkin lymphoma (HL). More than 20 years ago, the L428 HL cell line was reported to contain a small population of phenotypic B cells that appeared responsible for the continued generation of HRS cells. This observation, however, has never been corroborated, and such clonotypic B cells have never been documented in HL patients. We found that both the L428 and KM-H2 HL cell lines contained rare B-cell subpopulations responsible for the generation and maintenance of the predominant HRS cell population. The B cells within the HL cell lines expressed immunoglobulin light chain, the memory B-cell antigen CD27, and the stem cell marker aldehyde dehydrogenase (ALDH). Clonal CD27(+)ALDH(high) B cells, sharing immunoglobulin gene rearrangements with lymph node HRS cells, were also detected in the blood of most newly diagnosed HL patients regardless of stage. Although the clinical significance of circulating clonotypic B cells in HL remains unclear, these data suggest they may be the initiating cells for HL.

| S-EPMC2700327 | biostudies-literature

Correlations between baseline <sup>18</sup>F-FDG PET tumour parameters and circulating DNA in diffuse large B cell lymphoma and Hodgkin lymphoma.

Project description:Background18F-FDG PET/CT is a standard for many B cell malignancies, while blood DNA measurements are emerging tools. Our objective was to evaluate the correlations between baseline PET parameters and circulating DNA in diffuse large B cell lymphoma (DLBCL) and classical Hodgkin lymphoma (cHL).MethodsTwenty-seven DLBCL and forty-eight cHL were prospectively included. Twelve PET parameters were analysed. Spearman's correlations were used to compare PET parameters each other and to circulating cell-free DNA ([cfDNA]) and circulating tumour DNA ([ctDNA]). p values were controlled by Benjamini-Hochberg correction.ResultsAmong the PET parameters, three different clusters for tumour burden, fragmentation/massiveness and dispersion parameters were observed. Some PET parameters were significantly correlated with blood DNA parameters, including the total metabolic tumour surface (TMTS) describing the tumour-host interface (e.g. ρ = 0.81 p < 0.001 for [ctDNA] of DLBLC), the tumour median distance between the periphery and the centroid (medPCD) describing the tumour's massiveness (e.g. ρ = 0.81 p < 0.001 for [ctDNA] of DLBLC) and the volume of the bounding box including tumours (TumBB) describing the disease's dispersion (e.g. ρ = 0.83 p < 0.001 for [ctDNA] of DLBLC).ConclusionsSome PET parameters describing tumour burden, fragmentation/massiveness and dispersion are significantly correlated with circulating DNA parameters of DLBCL and cHL patients. These results could help to understand the pathophysiology of B cell malignancies.

| S-EPMC7541805 | biostudies-literature

Construction of relapse-related lncRNA-mediated ceRNA networks in Hodgkin lymphoma.

Project description:IntroductionHodgkin lymphoma (HL) is a type of lymphoma common throughout the western countries. However, the detailed mechanisms and special biomarkers of HL remain to be further investigated. Emerging studies have shown that long non-coding RNAs play a key role in human cancers.Material and methodsIn the present work, we constructed relapse-related lncRNA-mediated ceRNA networks in HL. Additionally, we constructed co-expression networks for these relapse-related lncRNAs. We also constructed a relapse-related lncRNA-miRNA-mRNA network to study the potential mechanism of these lncRNAs. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to explore functions of DEGs in Hodgkin lymphoma.ResultsA total of 18 lncRNAs were found to be dysregulated between early relapse and late relapse HL. Six lncRNAs (PCBP1-AS1, HCG18, GAS5, PSMD6-AS2, PRKCQ-AS1, SNHG6), 116 mRNAs and 121 miRNAs were included in the ceRNA network. Bioinformatics analyses revealed that these lncRNAs were significantly involved in regulating immune system processes, responses to chemical stimuli and responses to stress. Among them, HCG18 and PCBP1-AS1 were identified as key lncRNAs in HL relapse.ConclusionsOur results for the first time constructed the key relapse-related lncRNA-mediated ceRNA networks in Hodgkin lymphoma progression. We trust that this work will provide a new therapeutic and prognostic target for HL.

| S-EPMC7667426 | biostudies-literature

Double-refractory Hodgkin lymphoma: tackling relapse after brentuximab vedotin and checkpoint inhibitors.

Project description:The approval of brentuximab vedotin (BV) and checkpoint inhibitors (CPI) has revolutionized the management of relapsed/refractory classical Hodgkin lymphoma (cHL) patients. In recent years these agents have rapidly moved to earlier lines of therapy, including post-autologous hematopoietic cell transplant (auto-HCT) consolidation, pre-HCT salvage, and the frontline treatment setting. This shift in practice means that double-refractory (refractory to both BV and CPI) cHL is becoming an increasingly common clinical problem. In patients who are not eligible for clinical trials, conventional cytotoxic and targeted therapies (off label) may be a potential option. In patients who are transplant eligible, early referral to allogeneic HCT should be considered given the significant improvement in transplant outcomes in the contemporary era. Cellular therapy options including CD30.chimeric antigen receptor T cells, Epstein-Barr virus-directed cytotoxic T cells, and CD16A/30 bispecific natural killer cell engagers appear promising and are currently in clinical trials.

| S-EPMC8791097 | biostudies-literature

Defining the Inflammatory Plasma Proteome in Pediatric Hodgkin Lymphoma.

Project description:Hodgkin lymphoma (HL) histopathology is characterized by rare malignant Reed-Sternberg cells among an inflammatory infiltrate. We hypothesized that characteristics of inflammation in pediatric HL lesions would be reflected by the levels of inflammatory cytokines or chemokines in pre-therapy plasma of children with HL. The study objectives were to better define the inflammatory pre-therapy plasma proteome and identify plasma biomarkers associated with extent of disease and clinical outcomes in pediatric HL. Pre-therapy plasma samples were obtained from pediatric subjects with newly diagnosed HL and healthy pediatric controls. Plasma concentrations of 135 cytokines/chemokines were measured with the Luminex platform. Associations between protein concentration and disease characteristics were determined using multivariate permutation tests with false discovery control. Fifty-six subjects with HL (mean age: 13 years, range 3-18) and 47 controls were analyzed. The cytokine/chemokine profiles of subjects with HL were distinct from controls, and unique cytokines/chemokines were associated with high-risk disease (IL-10, TNF-α, IFN-γ, IL-8) and slow early response (CCL13, IFN-λ1, IL-8). TNFSF10 was significantly elevated among those who ultimately relapsed and was significantly associated with worse event-free survival. These biomarkers could be incorporated into biologically based risk stratification to optimize outcomes and minimize toxicities in pediatric HL.

| S-EPMC7761312 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data