Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Plasma cell-free mRNA profiles the immune response and myocardial damage in immune checkpoint inhibitor-induced myocarditis

ABSTRACT: Immune checkpoint inhibitor-induced myocarditis (ICI-m) is a highly fatal cancer treatment complication with challenging diagnosis and invasive diagnostic methods. We developed a plasma cell-free mRNA (cf-mRNA) platform for noninvasive characterization of the immune and myocardial landscape in ICI-m. We sequenced bulk cell-free total RNA from plasma of cancer patients treated with ICIs: without immune-related adverse events (irAE) (group A, n=5), with noncardiac irAE (group B, n=7), and with ICI-m with/without noncardiac irAE (group C, n=10). Publicly available healthy control cfRNA (n=30) served as external controls. Cell type-specific gene panels from single cell RNA-sequencing of circulating immune and cardiac cells were used for cellular deconvolution. Cancer and inflammatory pathways were enriched in ICI-treated patients versus controls. Cardiac pathways and conduction system genes were significantly enriched in group C versus A and B. Temra CD8+ T cell and cardiomyocyte signature scores, with CCL5 and MYH6 expression, were elevated in group C. Our custom ICI-m classifier, containing three cardiac- and three immune cell-specific genes, effectively differentiated group C from A (AUC 0.903, 95% CI 0.858-0.903) and B patients (AUC 0.983, 95% CI 0.970-0.983), outperforming unsupervised feature selection. outperforming unsupervised feature selection. This platform captures disease-specific signatures enabling precision diagnostics for inflammatory diseases.

ORGANISM(S): Homo sapiens

PROVIDER: GSE296680 | GEO | 2025/05/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Seven-lncRNA signature in esophageal squamous cell carcinoma

Project description:A seven-lncRNA signature was identified in the training set, which is significantly associated with overall survival (OS) (Hazard Ratio [HR]: 3.535, 95% confidence interval [CI]: 2.113-5.915, P < 0.001) and disease-free survival (DFS) (Hazard Ratio [HR]: 2.413, 95% confidence interval [CI]: 1.573-3.703, P < 0.001). Patients in high-risk group have shorter overall survival (HR: 3.555, 95% CI: 2.195-5.757, p < 0.001) and disease-free survival (HR: 2.537, 95% CI: 1.646-3.909, p < 0.001) in the training set, and we found the same conclusion in the independent set for OS (HR 2.665, p < 0.001) and DFS (HR 2.360, p = 0.001). Combination of the signature and TNM staging system was more powerful than TNM staging system alone in predicting outcomes in both the training set (AUC: 0.772 vs 0.681, p = 0.002) and in the independent set (AUC: 0.772 vs 0.660, p = 0.003).

2020-02-10 | GSE92986 | GEO

Inhibition of the IL-17A axis Protects against Immune-related Adverse Events while Supporting Checkpoint Inhibitor Anti-tumor Efficacy [RNA-seq (human)]

Project description:Checkpoint inhibitor (ICI) immunotherapy leverages the body’s own immune system to attack cancer cells but leads to unwanted autoimmune side effects in up to 60% of patients. Such immune related adverse events (IrAE) lead to treatment interruption, permanent organ dysfunction, hospitalization and premature death. Thyroiditis is one of the most common IrAE, but the cause of thyroid IrAE remains unknown. Here we present a novel mouse model in which checkpoint inhibitor therapy leads to multi-organ autoimmune infiltrates and show that activation and infiltration of Type 3 immune cells including IL17A+ RORt+ CD4+ (T helper 17 or Th17) and gamma delta 17 (T17) T cells promote thyroid IrAE development. In parallel, Th17 and T17 cells were similarly expanded in cancer patients treated with ICI. Furthermore, antibody-based inhibition of IL-17A, a clinically available therapy, significantly reduced thyroid IrAE development in ICI-treated mice. Finally, combination of IL-17A neutralization with ICI treatment in a mouse tumor model did not reduce ICI anti-tumor efficacy and indeed showed a trend toward enhancement. These studies suggest that targeting Th17 and 17 function may reduce IrAE without impairing ICI anti-tumor efficacy and may be a generalizable strategy to address IL17-mediated IrAE.

2023-12-31 | GSE192580 | GEO

Inhibition of IL-17A Protects against Thyroid Immune-related Adverse Events while Preserving Checkpoint Inhibitor Anti-tumor Efficacy [RNA-seq (murine)]

Project description:Checkpoint inhibitor (ICI) immunotherapy leverages the body’s own immune system to attack cancer cells but leads to unwanted autoimmune side effects in up to 60% of patients. Such immune related adverse events (IrAE) lead to treatment interruption, permanent organ dysfunction, hospitalization and premature death. Thyroiditis is one of the most common IrAE, but the cause of thyroid IrAE remains unknown. Here we present a novel mouse model in which checkpoint inhibitor therapy leads to multi-organ autoimmune infiltrates and show that activation and infiltration of Type 3 immune cells including IL17A+ RORgt+ CD4+ (T helper 17 or Th17) and gamma delta 17 (gdT17) T cells promote thyroid IrAE development. In parallel, Th17 and gdT17 cells were similarly expanded in cancer patients treated with ICI. Furthermore, antibody-based inhibition of IL-17A, a clinically available therapy, significantly reduced thyroid IrAE development in ICI-treated mice. Finally, combination of IL-17A neutralization with ICI treatment in a mouse tumor model did not reduce ICI anti-tumor efficacy and indeed showed a trend toward enhancement. These studies suggest that targeting Th17 and gd17 function may reduce IrAE without impairing ICI anti-tumor efficacy and may be a generalizable strategy to address IL17-mediated IrAE.

2022-11-21 | GSE176561 | GEO

miRNA sequencing of serum exosomes from hepatocellular carcinoma and liver cirrhosis patients

Project description:Exosomal microRNAs have recently been studied as potential diagnostic marker for various malignancies, including hepatocellular carcinoma (HCC). The aim of this study was to investigate serum exosomal microRNA profiles as HCC diagnostic marker. Transmission electron microscopy and western blot were used to identify serum exosomes. Deep sequencing was performed to screen differentially expressed microRNAs between HCC (n=5) and liver cirrhosis (LC, n=5) group. Three upregulated and two downregulated microRNAs were selected for qPCR analysis. The levels of selected microRNAs were normalized to Caenorhabditis elegans miR-39 microRNA mimics. Serum exosomal level of miR-122, miR-148a, and miR-1246 were further analyzed and significantly higher in HCC than LC and normal control (NC) group (P<0.001), but not different from chronic hepatitis group(p>0.05). The receiver operating characteristic curve was used to evaluate diagnostic perfromance of candidate microRNAs. Area under the curve (AUC) of miR-148a was 0.891 [95 % confidence interval (CI), 0.809-0.947] in discriminating HCC from LC, remarkably higher than alpha fetoprotein (AFP) (AUC: 0.712, 95 % CI: 0.607-0.803). Binary logistic regression was adpoted to establish the diagnostic model for discriminating HCC from LC. And the combination of miR-122, miR-148a and AFP increased the AUC to 0.931 (95% CI, 0.857-0.973), which can also be applied for distinguishing early HCC from LC. miR-122 was the best for differentiating HCC from NC (AUC: 0.990, 95% CI, 0.945-1.000). These data suggests that serum exosomal microRNAs signature or their combination with traditional biomarker may be used as a suitable peripheral screening tool for HCC.

2018-10-01 | GSE104251 | GEO

Genome-wide DNA methylation markers associated with metabolic liver cancer

Project description:Background and Aims: Metabolic liver disease is the fastest rising cause of hepatocellular carcinoma (HCC) worldwide, but the underlying molecular processes that drive HCC development in the setting of metabolic perturbations are unclear. We investigated the role of aberrant DNA methylation in metabolic HCC development in a multicenter international study. Results: We enrolled 272 metabolic HCC patients and 316 control patients with metabolic liver disease from six sites. Fifty-five differentially methylated CpGs were identified; 33 hypermethylated and 22 hypomethylated in cases versus controls. The panel of 55 CpGs discriminated between cases and controls with AUC=0.79 (95%CI=0.71-0.87), sensitivity=0.77 (95%CI=0.66-0.89), and specificity=0.74 (95%CI=0.64-0.85). The 55-CpG classifier panel performed better than a base model that comprised age, sex, race, and diabetes mellitus (AUC=0.65, 95%CI=0.55-0.75, sensitivity=0.62 (95%CI=0.49-0.75) and specificity=0.64 (95%CI=0.52-0.75). A multifactorial model that combined the 55 CpGs with age, sex, race, and diabetes, yielded AUC=0.78 (95%CI=0.70-0.86), sensitivity=0.81 (95%CI=0.71-0.92), and specificity=0.67 (95%CI=0.55-0.78). Conclusions: A panel of 55 blood leukocyte DNA methylation markers differentiates patients with metabolic HCC from control patients with benign metabolic liver disease, with a slightly higher sensitivity when combined with demographic and clinical information.

2025-02-26 | GSE281691 | GEO

Interleukin 21 drives CXCR6+ CD8+ T cell mediators in Autoimmune Checkpoint Inhibitor Thyroiditis

Project description:Checkpoint inhibitor (ICI) immunotherapy leverages the body’s own immune system to attack cancer cells but leads to unwanted autoimmune side effects in up to 60% of patients. Such immune related adverse events (IrAE) lead to treatment interruption, permanent organ dysfunction, hospitalization and premature death. Thyroiditis is one of the most common IrAE, but the cause of thyroid IrAE remains unknown. To delineate human IRAE pathogenesis, we sampled thyroid tissue from subjects with ICI-thyroiditis and HT. Using single cell RNA sequencing of human thyroid fine needle aspiration (FNA) specimens, we identify CXCR6+ interferon gamma (IFN)+ cytotoxic CD8+ T cells as key contributors to ICI-thyroiditis (IRAE). This is in contrast to the primary role for CD4+ Th17 cells in the pathogenesis of HT (14, 15). Interestingly, we also found a supporting role for IL21-producing CD4+ T follicular (Tfh) and peripheral helper (Tph) cells via the upregulation of CXCR6 and cytotoxic function in CD8+ T cells.

2023-05-17 | GSE218743 | GEO

Human tRF & tiRNA sequencing of SLE and LN patients

Project description:We first analyzed tsRNA signatures in SLE serum and identified that tRF-His-GTG-1 was significantly upregulated in SLE serum. The combination of tRF-His-GTG-1 and anti-dsDNA could serve as biomarkers for diagnosing SLE with a high AUC of 0.95 (95% CI=0.92-0.99), sensitivity (83.72%) and specificity (94.19%). Importantly, the non-invasive serum tRF-His-GTG-1 could also be used to distinguish SLE with LN or SLE without LN with AUC of 0.81 (95% CI, 0.73–0.88) and performance (sensitivity 66.27%, specificity 96.15%). Moreover, the serum tsRNA is mainly secreted via exosome and directly target signaling molecules that play crucial roles in regulating the immune system.

2021-11-09 | GSE179950 | GEO

MicroRNAs Biomarkers and Host Response Pathways in Severe Pulmonary Hemorrhagic Syndrome due to Leptospirosis

Project description:Serum microRNA profiling revealed distinct expression patterns between the two phenotypes. From the top 81 significantly expressed microRNAs, seven were selected for validation. Among these, miR-5010-3p and miR-147b-3p had area under the curve (AUC) values of 0.72 (95% CI: 0.62–0.81) and 0.66 (95% CI: 0.55–0.76) for discriminating SPHS. Notably, the two microRNAs could detect SPHS in patients who were yet to manifest chest radiograph shadows at the time of sample collection, with consistent AUC values.

2025-04-09 | GSE283845 | GEO

Early isolated v-lesion may not truly represent a rejection of kidney allograft

Project description:Intimal arteritis is known to be a negative prognostic factor for kidney allograft survival. Although Banff classification assesses isolated v-lesion (IV) as a T-cell mediated rejection, its origin and significance remain unclear. To help resolve if IV truly represents acute rejection, molecular study was performed. Transcriptome of early IV, T cell-mediated vascular rejection (TCMRV) and nonrejection histologic findings was compared using microarrays (Illumina Human HT-12 v4 Expression BeadChips). The enrichment of deregulated genes was analysed using DAVID. Differential gene expression analysis identified 310 genes to be deregulated in TCMRV compared to IV. Gene enrichment analysis categorized deregulated genes to be associated with immune and inflammatory response. Principal component and unsupervised hierarchical cluster analysis revealed clear distinction of TCMRV samples but showed similarity of IV with control group. RT-qPCR validation on external sample set (n=20) confirmed upregulation of genes involved in immune response in TCMRV compared to IV. Based on stepwise logistic regression SLA2 gene represented the strongest group classifier [OR 0.106 (95 % CI 0.01- 0.774), p=0.03] with ROC AUC 0.906 [95% CI (0.769-1.0), p=0.003)]. IV reveals weak immunologic signature compared to TCMRV but shows similarity with non-rejection findings. Early IV in a DSA- and C4d- negative patients may feature non-rejection origin and reflect injury distinct from alloimmune response. Study calls for reassessment of current Banff histopathology criteria which considers an intimal arteritis to be TCMR irrespective of TI and supports use of molecular diagnostics as a part of integrative approach.

2018-05-22 | GSE114712 | GEO

Clinical and Biomarker Results from A Phase II Trial of Combined Cabozantinib and Durvalumab in Patients with Chemotherapy-refractory Colorectal Cancer (CRC): CAMILLA CRC Cohort

Project description:CAMILLA is a basket trial (NCT03539822) evaluating cabozantinib plus the ICI durvalumab in chemorefractory gastrointestinal cancer. Herein, are the phase II colorectal cohort results. 29 patients were evaluable. 100% had confirmed pMMR/MSS tumors. Primary endpoint was met with ORR of 27.6% (95% CI 12.7-47.2%). Secondary endpoints of 4-month PFS rate was 44.83% (95% CI 26.5-64.3%); and median OS was 9.1 months (95% CI 5.8-20.2). Grade≥3 TRAE occurred in 39%. In post-hoc analysis of patients with RAS wild type tumors, ORR was 50% and median PFS and OS were 6.3 and 21.5 months respectively. Exploratory spatial transcriptomic profiling of pretreatment tumors showed upregulation of VEGF and MET signaling, increased extracellular matrix activity and pre-existing anti-tumor immune responses coexisting with immune suppressive features like T cell migration barriers in responders versus non-responders. Cabozantinib plus durvalumab demonstrated anti-tumor activity, manageable toxicity, and have led to the activation of the phase III STELLAR-303 trial.

2024-01-27 | GSE254054 | GEO

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