MicroRNA expression levels in plasma exosomes from liver cancer patients before and after surgery [miRNA-Seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE262616 | GEO | 2025/03/28
REPOSITORIES: GEO
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Project description:Treatment options and reliable predictive marker to determine patients at risk to develop postoperative LD and to define the optimal time point of liver resection are limited. Accordingly, there is an urgent need for an easily assessable preoperative test to predict postoperative liver function recovery, specifically as current markers are often expensive, time consuming and sometimes invasive. Emerging evidence suggests that microRNA (miRNA) signatures represent potent diagnostic, prognostic and treatment response biomarkers for several diseases. Using next-generation sequencing as an unbiased systematic approach 554 miRNAs were detected in preoperative plasma of 21 patients suffering from postoperative LD after liver resection and 27 matched controls. Subsequently, we identified a miRNA signature - consisting of miRNAs 151a-5p, 192-5p and 122-5p - that highly correlated with patients developing postoperative LD after liver resection. The predictive potential for postoperative LD was subsequently confirmed using real-time PCR in an independent validation cohort of 98 patients. Ultimately, a regression model of the two miRNA ratios 151a-5p to 192-5p and 122-5p to 151a-5p was found to reliably predict postoperative LD, severe morbidity, prolonged intensive care unit and hospital stay and even mortality prior to surgery with a remarkable accuracy, thereby outperforming established markers of postoperative LD. Ultimately, we documented that miRNA ratios closely followed liver function recovery after partial hepatectomy. Conclusion: Given the clinical relevance of predicting potentially fatal postoperative clinical outcome after liver resection, our data demonstrate the clinical utility of a novel miRNA-based biomarker to support the selection of patients undergoing partial hepatectomy. The dynamical changes during liver function recovery indicate a possible role in tailoring the optimal time point of surgery to each individual patient. Thereby, our data might help to tailor surgical strategies to the specific risk profile of individual patients.
2019-06-30 | GSE123605 | GEO
Project description:MicroRNAs (miRNAs) are intrinsic regulators in the various cellular processes, and their abnormalities are considered to be involved in the onset of human disorders, including cancer. Circulating miRNA is focused as new cancer biomarker however it is regarded that circulating RNA are released not only from tumor but also by various pathways. Recently, exosomes, small membrane vesicles, have been a major interest in cancer research field, because of their unique biological properties. Exosomes are secreted from various cells and the components (Lipids, mRNAs, miRNAs and proteins) reflect origin of the cells secreting them. Identification of exosomal miRNAs from cancer cells is expected to provide useful biomarkers of cancer. To identify specific exosomal miRNAs as candidate biomarkers for colorectal cancer, we profiled exosomal miRNAs in sera of colon cancer patients (n=88) at various TNM stages (I to IV) and healthy controls (n=11) and selected significantly higher microRNAs in serum exosomes of colorectal cancer patients than that of healthy controls. Moreover, we tried to detect their serum exosome levels of using samples from patients after surgical resection of primary tumors (n=24). Serum exosomes were prepared by step-wise ultra-centrifugation methods in 24 colorectal cancer patients (age; 35-65) after surgical resection of primary tumor (TNM stage I; n=6, stage II; n=5, stage IIIa; n=5, stage IIIb; n=5, stage IV; n=3) .Exosome fraction was mixed with Trizol-LS reagent (Invitrogen), and aqueous phase was collected by adding chloroform. After addition of ethanol to the aqueous phase, it was placed on to an RNeasy mini spin column (Qiagen) for the purification of total RNAs. The total RNAs were analyzed by Agilent Human miRNA V3 Microarray (G4470C) according to the manufacturer's instructions.
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Project description:MicroRNAs (miRNAs) are intrinsic regulators in the various cellular processes, and their abnormalities are considered to be involved in the onset of human disorders, including cancer. Circulating miRNA is focused as new cancer biomarker however it is regarded that circulating RNA are released not only from tumor but also by various pathways. Recently, exosomes, small membrane vesicles, have been a major interest in cancer research field, because of their unique biological properties. Exosomes are secreted from various cells and the components (Lipids, mRNAs, miRNAs and proteins) reflect origin of the cells secreting them. Identification of exosomal miRNAs from cancer cells is expected to provide useful biomarkers of cancer. To identify specific exosomal miRNAs as candidate biomarkers for colorectal cancer, we profiled exosomal miRNAs in sera of colon cancer patients (n=88) at various TNM stages (I to IV) and healthy controls (n=11) and selected significantly higher microRNAs in serum exosomes of colorectal cancer patients than that of healthy controls. Moreover, we tried to detect their serum exosome levels of using samples from patients after surgical resection of primary tumors (n=24). Serum exosomes were prepared by step-wise ultra-centrifugation methods in 11 healthy controls and 88 colorectal cancer patients with various TNM stages (I; n=20, stage II; n=20, stage IIIa; n=20, stage IIIb: n=16, stage IV; n=12) (age; 35-65) .Exosome fraction was mixed with Trizol-LS reagent (Invitrogen), and aqueous phase was collected by adding chloroform. After addition of ethanol to the aqueous phase, it was placed on to an RNeasy mini spin column (Qiagen) for the purification of total RNAs. The total RNAs were analyzed by Agilent Human miRNA V3 Microarray (G4470C) according to the manufacturer's instructions.
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Project description:Eicosapentaenoic acid in its free fatty acid form (EPA-FFA), 2g daily, is safe and well-tolerated in patients undergoing liver resection surgery for colorectal liver metastasis.Oral EPA incorporates into colorectal liver metastasis tissue. EPA-FFA treatment is associated with reduced vascularity of liver metastases in Ï-3 PUFA-naïve patients. Preoperative (median 30 days) EPA-FFA treatment may have prolonged benefit on postoperative overall and disease-free survival. We used whole genome expression array to study whether systemic CCL2 level changes were linked to a specific tumour gene expression profile in colorectal liver metastasis patients treated with EPA-FFA. 15 tumour RNA samples from colorectal liver metastasis patients treated with EPA-FFA during the EMT study (ClinicalTrials.gov NCT01070355) were extracted from formalin-fixed paraffin-wax embedded tissue blocks. The RNA samples were used for whole genome expression microarray experiments. We then performed a differential gene expression analysis to compare the tumour expression profile of patients with increased or decreased plasma CCL2 levels after intervention.
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Project description:Tumor-derived exosomes are emerging as mediators of tumorigenesis with a tissue-specific address and message. We explored the function of melanoma-derived exosomes in formation of primary tumors and metastatic progression in both murine models and patients. Whereas exosomes from highly metastatic melanoma cells increased the metastatic behavior of primary tumor cells by educating bone marrow (BM) progenitor cells via the MET receptor, exosomes from low metastatic melanoma cells did not alter the incidence of metastases. Melanoma-derived exosomes induced vascular leakiness at pre-metastatic sites, and reprogrammed BM progenitor cells towards a pro-vasculogenic phenotype (c-Kit+Tie2+MET+). Reducing MET expression in tumor-derived exosomes diminished the pro-metastatic behavior of BM cells. Importantly, MET expression was upregulated in circulating BM progenitor cells (CD45-CD117low and CD45-CD117lowTIE2+) isolated from stage III and stage IV melanoma patients. Rab1a, Rab5b, Rab7, and Rab27a were highly expressed in melanoma and Rab27a RNA interference decreased exosome production and/or soluble angiogenic factors in melanoma cells, thereby preventing mobilization of BM progenitor cells, tumor growth and metastasis. Finally, we identified a melanoma signature in exosomes isolated from metastatic melanoma patients, comprised of TYRP2, VLA-4, Hsp70, an Hsp90 isoform and MET oncoprotein, which together with Rab proteins, appear to represent exosome-specific proteins with prognostic potential, and may provide new therapeutic targets. Identification of molecular finger associated to exosome effects in metastatic organs Microarray analysis of genes differentially expressed in the lungs 24 and 48 hours after B16-F10 exosome tail vein injection compared to control.
2012-05-26 | E-GEOD-36584 | biostudies-arrayexpress
Project description:This experiment aimed to investigate whether exosomess released by IPSC-cardiomyocytes during hypoxia can positively influence cardiac electrophysiology and miRNA expression during hypoxic stress. A multielectrode array (MEA) system was used as an in vitro method of recording real-time cardiac electrophysiological activity, highlighting the biological effects facilitated by exosomes. Additionally, miRNA-sequencing was performed to compare miRNA expressions in exosome-preconditioned and non-preconditioned IPSC-cardiomyocytes, elucidating important modulators of cardiac electrophysiology.
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Project description:Cardiac surgery and cardiopulmonary bypass induce a substantial immune and inflammatory response, the overactivation of which is associated with significant complications. Longitudinal DNA methylation profiling allows the potential to identify changes in gene regulatory mechanisms that are secondary to surgery and to identify molecular processes that predict and/or cause postoperative complications. In this study, we measure DNA methylation in preoperative and postoperative whole blood samples from 96 patients undergoing cardiac surgery on cardiopulmonary bypass. We identify several loci with statistically significant postoperative changes in methylation. Additionally, two of these loci are associated with new-onset postoperative atrial fibrillation, a significant complication after cardiac surgery. This research establishes that there are statistically significant changes in DNA methylation that occur immediately after cardiac surgery and that these acute alterations in DNA methylation have the granularity to identify processes associated with major postoperative complications.
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