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Project description:Pluripotent stem cell-derived small extracellular vesicles (PSC-sEVs) have demonstrated great clinical translational potential in multiple aging-related degenerative diseases. Characterizing the PSC-sEVs is crucial for their clinical applications. However, the specific biomarker pattern of PSC-sEVs remains unknown. We displayed proteome analysis and further verification for identification of PSC-sEVs' specific biomarkers. The application of these specific biomarkers for PSC-sEVs identification may advance the clinical translation of PSCs-sEVs.
2024-05-23 | PXD047171 | Pride
Project description:Background & Aims: Cholangiocarcinomas (CCAs), heterogeneous biliary tumors with dismal prognosis, lack accurate early-diagnostic methods, especially important for individuals at high-risk (i.e., primary sclerosing cholangitis (PSC)). Here, we searched for protein biomarkers in serum extracellular vesicles (EVs). Methods: EVs from patients with isolated PSC (n=45), concomitant PSC-CCA (n=42), PSC who developed CCA during follow-up (PSC to CCA; n=25), CCAs from non-PSC etiology (n=56), hepatocellular carcinoma (n=34) and healthy individuals (n=55) were characterized by mass-spectrometry. Diagnostic biomarkers of PSC-CCA, non-PSC CCA or CCAs regardless etiology (pan-CCAs) were defined, and their expression was evaluated in human organs/tissues and within CCA tumors at single-cell level. Prognostic EV-biomarkers for CCA were investigated. Results: High-throughput proteomics identified candidate diagnostic biomarkers for PSC-CCA, non-PSC CCA or pan-CCA, as well as and for differential diagnosis of intrahepatic CCA and HCC, that were cross-validated by ELISA using total serum. Machine learning logit modelling disclosed CRP/FRIL/Fibrinogen algorithm with diagnostic value for early-stage PSC-CCA vs isolated PSC (AUC=0.944; OR=82.0), overpowering CA19-9 (AUC=0.735; OR=9.3). An algorithm combining CRP/VWF/PIGR/ /Fibrinogen allowed the diagnosis of early-stage non-PSC CCAs compared to healthy individuals (AUC=0.999; OR=1115). Noteworthy, levels of Fibrinogen/CRP/PIGR/FRIL showed predictive capacity for CCA development in patients with PSC before clinical evidences of malignancy. Multi-organ transcriptomic analysis revealed that serum EV-biomarkers were mostly expressed in hepatobiliary tissues, and scRNA-seq and immunofluorescence analysis of CCA tumors showed their presence mainly in malignant cholangiocytes. Multivariable analysis unveiled EVprognostic biomarkers independent to clinical features, with COMP/GNAI2/CFAI and ACTN1/MYCT1/PF4V associated negatively or positively to patients’ survival, respectively. Conclusions: Serum EVs contain protein biomarkers for the prediction, early diagnosis and prognosis estimation of CCA, representing a novel tumor cell-derived liquid biopsy for personalized medicine.
2023-07-20 | PXD036943 | Pride
Project description:Background & Aims: Cholangiocarcinomas (CCAs), heterogeneous biliary tumors with dismal prognosis, lack accurate early-diagnostic methods, especially important for individuals at high-risk (i.e., primary sclerosing cholangitis (PSC)). Here, we searched for protein biomarkers in serum extracellular vesicles (EVs). Methods: EVs from patients with isolated PSC (n=45), concomitant PSC-CCA (n=42), PSC who developed CCA during follow-up (PSC to CCA; n=25), CCAs from non-PSC etiology (n=56), hepatocellular carcinoma (n=34) and healthy individuals (n=55) were characterized by mass-spectrometry. Diagnostic biomarkers of PSC-CCA, non-PSC CCA or CCAs regardless etiology (pan-CCAs) were defined, and their expression was evaluated in human organs/tissues and within CCA tumors at single-cell level. Prognostic EV-biomarkers for CCA were investigated. Results: High-throughput proteomics identified candidate diagnostic biomarkers for PSC-CCA, non-PSC CCA or pan-CCA, as well as and for differential diagnosis of intrahepatic CCA and HCC, that were cross-validated by ELISA using total serum. Machine learning logit modelling disclosed CRP/FRIL/Fibrinogen algorithm with diagnostic value for early-stage PSC-CCA vs isolated PSC (AUC=0.944; OR=82.0), overpowering CA19-9 (AUC=0.735; OR=9.3). An algorithm combining CRP/VWF/PIGR/ /Fibrinogen allowed the diagnosis of early-stage non-PSC CCAs compared to healthy individuals (AUC=0.999; OR=1115). Noteworthy, levels of Fibrinogen/CRP/PIGR/FRIL showed predictive capacity for CCA development in patients with PSC before clinical evidences of malignancy. Multi-organ transcriptomic analysis revealed that serum EV-biomarkers were mostly expressed in hepatobiliary tissues, and scRNA-seq and immunofluorescence analysis of CCA tumors showed their presence mainly in malignant cholangiocytes. Multivariable analysis unveiled EVprognostic biomarkers independent to clinical features, with COMP/GNAI2/CFAI and ACTN1/MYCT1/PF4V associated negatively or positively to patients’ survival, respectively. Conclusions: Serum EVs contain protein biomarkers for the prediction, early diagnosis and prognosis estimation of CCA, representing a novel tumor cell-derived liquid biopsy for personalized medicine.
2023-07-20 | PXD037007 | Pride
Project description:The presence of mutations in human pluripotent stem cells (PSC), whether embryonic stem (ESC) cells, or induced pluripotent stem (iPSC) cells, is a concern for their safe use in therapeutic applications. Indeed, in one case, a potential trial of retinal pigment cells from an autologous iPS cell line was abandoned because the cells carried a mutation of unknown significance (Mandai et al. 2017). Certainly some such variants are likely to have been present in the embryos or somatic cells from which particular PSC were derived and can be classed as ‘variants of origin’ (Amps et al. 2011). However, the propensity of PSC to acquire genetic variants on prolonged passage poses additional concerns, not only because of the difficulty for their early detection (Baker et al. 2016), but also their selective growth advantages might presage malignant potential (Andrews et al. 2017). In this study, to determine the rate and types of mutation that occur during culture of human PSC, we have used a cloning strategy coupled with whole genome- and RNA-sequencing to compare two well characterized, clinical grade human ES cell lines, as well as the effects of culture in the presence of a Rho kinase inhibitor, now commonly used in routine culture of human PSC, and of culture under low oxygen (5% O2) conditions. We have tested whether the mutations are randomly distributed throughout the genome or clustered in regions related to chromatin structure and gene expression. Our results indicate that the mutation rate is low compared to estimates in somatic or cancer cells, and can be further reduced by culture under low oxygen conditions. Furthermore, the mutational signature of human PSC is similar to that of other cultured human cells, but low oxygen culture does alter the frequency of some types of base pair change associated with oxidative damage.
2020-06-20 | GSE120794 | GEO
Project description:COBRA - clinical trial for colorectal cancer diagnosis from breath samples
2019-08-23 | MSV000084227 | MassIVE
Project description:Clinical isolate from vaccine trial
| PRJNA28511 | ENA