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.
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.
Project description:Background: Immunotherapy has increased the expected survival of patients with advanced HCC. However, objective radiological response to these therapies has been reported to occur in around 20% of patients. Our aim was to identify potential serological markers of response to ICIs. Methods: 25 patients with advanced HCC treated with immunotherapy were prospectively in-cluded. Cytokine and cfDNA/ctDNA levels were measured prior to first treatment administration (basal) and after 3 months of treatment. Basal ctDNA profiling was also analyzed. Results: Basal levels of CTLA-4, cfDNA and ctDNA were significantly different in patients presenting progres-sive disease as best radiological response. The percentage of patients with basal mutations in CDKN2A was significantly higher in patients presenting progressive disease and they have a significantly lower number of CNV. Levels at 3 months of starting the treatment of MCP-1, TNF-alpha, cfDNA and ctDNA were also significantly different between patients with and without progressive disease. Higher cfDNA and ctDNA levels were associated with a poorer overall survival. Conclusion: Analysis of cfDNA and cytokines could help to stratify patients according to expected response to immunotherapies.
Project description:This study aims to compared ctDNA methylation status induced by ionizing to different ograns. SD rats were irradiated with local radaition to brain, lung or skin. Serum was collected and subjiected to ctDNA extraction. ctDNA were then treated by methylation-sensive bisulfite and sequencing.
Project description:Medulloblastoma (MB) is an embryonal tumor of the cerebellum and a highly malignant childhood brain tumor. Cell-free circulating tumor DNA (ctDNA) from the cerebrospinal fluid (CSF) of patients with brain tumors faithfully represent genomic alterations of brain tumors. Distinct epigenetic signatures among subgroups of MB allow us to detect epigenetic alterations in CSF to aid classify and guide therapy of MB tumors. Here, we evaluate DNA methylation and hydroxymethylation of ctDNA derived from small amount of CSF (200 µL) and matched tumor DNA from 3 MB patients. We find highly concordance of DNA methylation and hydroxymethylation between CSF ctDNA and tumor DNA, especially in CpG islands. Importantly, CSF ctDNA can mostly recapitulate the dynamic changes of DNA methylation and hydroxymehtylation in tumor species compared to healthy cerebellums. Those MB tumor signature CpGs’ DNA methylation status are recovered in CSF ctDNA can clearly distinguish MB subgroups by utilizing public large cohort data. We further identified potential diagnostic and prognostic DNA methylation markers in CSF ctDNA. Our results show that CSF ctNDA methylation and hydroxymethylation can be a minimal invasive method to assess epigenetic alterations of MB, which is complementary to current diagnoses of MB tumors.
Project description:Minimal residual disease (MRD) after frontline treatment of advanced stage ovarian cancer remains a longstanding barrier to cure. We investigated the prognostic and translational value of MRD detection by second look laparoscopy (SLL) and circulating tumor DNA (ctDNA) at the completion of frontline therapy. Patients with high-grade epithelial ovarian cancer with complete clinical response to frontline therapy who underwent SLL and plasma collection for ctDNA were included. Progression-free survival (PFS) and overall survival (OS) were estimated based on MRD and clinicopathologic status. Spatial transcriptomics (GeoMx and Visium) and proteomics (CODEX) profiling were performed on serial samples from select patients. Forty of 95 (42.1%) patients had surgically detected MRD, and this was associated with worse PFS (median PFS 7.4 vs 23.8 months; p<0.001) and OS (median OS 33.9 vs not reached; p<0.001). SLL positivity was found to be an independent negative prognostic factor for OS (HR 4.40, 95% CI 1.37-14.21, p=0.013) in multivariable analysis. Among 44 patients who underwent SLL and had ctDNA testing, 34% (15/44) were ctDNA-positive, which was associated with worse PFS (6.4 vs 28.1 months; p<0.001) and OS (32.4 months vs not reached; p=0.008). We demonstrated the feasibility of spatial multi-omics in studying MRD, and their ability to provide hypothesis-generating observations, implicating the upregulation of the hypoxia signaling pathway, expression of multiple druggable targets (CDK6, GLS, MSLN, and ERBB2), and immune exclusion, in the development of MRD lesions. In summary, approximately half of patients in clinical remission after frontline therapy have assessable MRD which can inform prognosis, therapeutic target discovery, and clinical trials.
Project description:Medulloblastoma (MB) is an embryonal tumor of the cerebellum and a highly malignant childhood brain tumor. Cell-free circulating tumor DNA (ctDNA) from the cerebrospinal fluid (CSF) of patients with brain tumors faithfully represent genomic alterations of brain tumors. Distinct epigenetic signatures among subgroups of MB allow us to detect epigenetic alterations in CSF to aid classify and guide therapy of MB tumors. Here, we evaluate DNA methylation of ctDNA derived from small amount of CSF (200 µL) and matched tumor DNA from four subtypes of MB patients. We find highly concordance of DNA methylation between CSF ctDNA and tumor DNA in a subtype manner. Our results show that CSF ctNDA methylation can be a minimal invasive precisely method to assess epigenetic alterations of MB in a subtype manner, which is complementary to current diagnoses of MB tumors.
Project description:Medulloblastoma (MB) is an embryonal tumor of the cerebellum and a highly malignant childhood brain tumor. Cell-free circulating tumor DNA (ctDNA) from the cerebrospinal fluid (CSF) of patients with brain tumors faithfully represent genomic alterations of brain tumors. Distinct epigenetic signatures among subgroups of MB allow us to detect epigenetic alterations in CSF to aid classify and guide therapy of MB tumors. Here, we evaluate DNA methylation of ctDNA derived from small amount of CSF (200 µL) and matched tumor DNA from four subtypes of MB patients. We find highly concordance of DNA methylation between CSF ctDNA and tumor DNA in a subtype manner. Our results show that CSF ctNDA methylation can be a minimal invasive precisely method to assess epigenetic alterations of MB in a subtype manner, which is complementary to current diagnoses of MB tumors.