Elective colorectal cancer surgery in nonagenarians and postoperative outcomes
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer
PROVIDER: 2724350 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
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.
2023-01-09 | GSE215937 | GEO
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:Postoperative cognitive dysfunction (POCD) is one of the severe complications inducing low life quality and high mortality after surgery, especially in elderly patients.Here we probed differentially expressed circRNAs using microarray assay in POCD patients, aiming to find potential key circRNAs related to the occurrence of POCD. Subsequently, ten dysregulated circRNAs were confirmed via quantitative real-time polymerase chain reaction (qRT-PCR) in 10 paired samples. Then, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to probe the vital functions of dysregulated genes.
2020-07-14 | GSE147277 | GEO
Project description:In the past decades, ample evidence has shown that combined radio-chemotherapy is superior to either radiotherapy or chemotherapy alone in oligodendroglioma. However, the survival benefit comes at the cost of immediate and long-term toxicities. Therefore, deferring postoperative therapy until progression may be a valid option to delay treatment-related side effects. Still, systematic data and reliable predictive biomarkers are limited. In this large retrospective series of oligodendroglioma cases, we could show that early postoperative treatment is not associated with improved PFS and OS while correcting for baseline differences between both groups. In addition, we performed whole-genome DNA methylation analyses and observed a predictive role of certain methylation patterns independent from MGMT promoter methylation status, extent of resection and CNS WHO grade. The results of this real-life study may serve as a benchmark for future trial planning in oligodendroglioma, and further studies should evaluate the predictive value of DNA methylation profiles.
2022-08-22 | GSE209579 | GEO
Project description:This dataset is part of the European BioCog project (EU602461) and comprises perioperative plasma samples from elderly patients (≥65 years) undergoing elective surgery. Proteomic profiling was conducted in a matched case-control design to investigate molecular mechanisms of postoperative delirium (POD). Samples were collected preoperatively (T0) and on postoperative day 1 (T1).
2026-02-16 | PXD071265 | Pride
Project description:Objectives. Postoperative neurological complications (PONC), associated with substantial morbidity and mortality, represent a prevalent clinical challenge following surgical repair of acute type A aortic dissection (AAD). This study aimed to identify novel biomarkers for early diagnosis of PONC to facilitate timely clinical intervention. Methods. We established deep hypothermic circulatory arrest (DHCA) rat models, extracted total RNA from the hippocampus of rats (DHCA group and control group), performed miRNA sequencing, screened for differentially expressed genes (DEGs) between the two groups, and analyzed their associated biological processes (BP) and pathways. A cohort of 95 patients diagnosed with AAD was enrolled in this study. Comprehensive clinical assessments and a standardized neuropsychological test battery were systematically conducted. Serum miR-29 levels were quantified via reverse transcription quantitative real-time polymerase chain reaction. Results. Transcriptomic profiling of rat hippocampus under deep hypothermic circulatory arrest / cardiopulmonary bypass (DHCA/CPB) identified 37 differentially expressed miRNAs (|log2FC|≥1.3, P<0.05), with miR-29a-5p and miR-29b-3p showing the most significant dysregulation. Functional enrichment implicated MAPK signaling and junctional pathways in blood-brain barrier modulation. In a clinical cohort of 95 aortic dissection patients, the PONC group exhibited prolonged CPB time (164.00 (137.00, 193.00) vs. 140.00 (120.25, 161.00), P=0.012), elevated inflammatory biomarkers (pre-op interleukin-6: 106.60 vs. 47.00, P<0.001), and altered miR-29 expression profiles. Multivariate analysis confirmed preoperative miR-29b-3p (OR=2.53, 95%CI 1.17-5.47) and postoperative miR-29a-5p (OR=0.21, 95%CI 0.05-0.96) as independent PONC predictors. The nomogram demonstrated robust discrimination (AUC=0.867, 95%CI 0.771-0.963) and clinical utility (net benefit=0.23), with 30-day survival analysis revealing miR-29b-3p-associated mortality risk (HR=4.372, 95%CI 0.928-20.596, P=0.041). Conclusions. Dual-phase miR-29 dysregulation predicts PONC post-AAD repair, validated by a nomogram and miR-29b-3p-associated mortality risk, guiding early intervention strategies.
2026-04-13 | GSE298179 | GEO
Project description:The inflammatory response to surgery is essential for healing and recovery, however hyperinflammation and altered immune competence increases the risk of inflammation mediated complications. We hypothesised that, in some patients, a state of postoperative systemic inflammatory dysregulation (PSID) exists increasing the risk or infection and sepsis, and that this will be associated with, and potentially predicted by, altered patterns of genome-wide peripheral blood mononuclear cell differential DNA methylation and gene expression. In this study we utilised phenotypic extremes of postoperative plasma C-reactive protein levels to define PSID, which manifested clinically in significantly higher rates of sepsis, complications and longer hospital stays following major abdominal surgery. We identified altered DNA methylation and differential gene expression in specific immune and metabolic pathways during PSID. Our findings suggest that dysregulation results in, or from, dramatic changes in differential DNA methylation and highlights potential targets for early detection and treatment. The combination of altered DNA methylation and gene expression confirms that dysregulation is mediated at multiple levels within specific gene sets and hence, non-specific anti-inflammatory treatments such as corticosteroids alone are unlikely to represent an effective therapeutic strategy.
2021-09-17 | GSE184047 | GEO
Project description:The inflammatory response to surgery is essential for healing and recovery, however hyperinflammation and altered immune competence increases the risk of inflammation mediated complications. We hypothesised that, in some patients, a state of postoperative systemic inflammatory dysregulation (PSID) exists increasing the risk or infection and sepsis, and that this will be associated with, and potentially predicted by, altered patterns of genome-wide peripheral blood mononuclear cell differential DNA methylation and gene expression. In this study we utilised phenotypic extremes of postoperative plasma C-reactive protein levels to define PSID, which manifested clinically in significantly higher rates of sepsis, complications and longer hospital stays following major abdominal surgery. We identified altered DNA methylation and differential gene expression in specific immune and metabolic pathways during PSID. Our findings suggest that dysregulation results in, or from, dramatic changes in differential DNA methylation and highlights potential targets for early detection and treatment. The combination of altered DNA methylation and gene expression confirms that dysregulation is mediated at multiple levels within specific gene sets and hence, non-specific anti-inflammatory treatments such as corticosteroids alone are unlikely to represent an effective therapeutic strategy.
2021-09-17 | GSE184039 | GEO
Project description:Background: On-pump cardiac surgery triggers sterile inflammation and postoperative complications such as postoperative atrial fibrillation (POAF). Hematopoietic somatic mosaicism (HSM) is a recently identified risk factor for cardiovascular diseases and results in a shift toward a chronic proinflammatory monocyte transcriptome and phenotype. Objectives: The aim of this study was to assess the prevalence, characteristics, and impact of HSM on preoperative blood and myocardial myeloid cells as well as on outcomes after cardiac surgery. Methods: Blood DNA from 104 patients referred for surgical aortic valve replacement (AVR) was genotyped using the HemePACT panel (576 genes). Four screening methods were applied to assess HSM, and postoperative outcomes were explored. In-depth blood and myocardial leukocyte phenotyping was performed in selected patients using mass cytometry and preoperative and postoperative RNA sequencing analysis of classical monocytes. Results: The prevalence of HSM in the patient cohort ranged from 29%, when considering the conventional HSM panel (97 genes) with variant allelic frequencies ≥2%, to 60% when considering the full HemePACT panel and variant allelic frequencies ≥1%. Three of 4 explored HSM definitions were significantly associated with higher risk for POAF. On the basis of the most inclusive definition, HSM carriers exhibited a 3.5-fold higher risk for POAF (age-adjusted OR: 3.5; 95% CI: 1.52-8.03; P = 0.003) and an exaggerated inflammatory response following AVR. HSM carriers presented higher levels of activated CD64+CD14+CD16- circulating monocytes and inflammatory monocyte-derived macrophages in presurgery myocardium. Conclusions: HSM is frequent in candidates for AVR, is associated with an enrichment of proinflammatory cardiac monocyte-derived macrophages, and predisposes to a higher incidence of POAF. HSM assessment may be useful in the personalized management of patients in the perioperative period.
2023-03-15 | GSE190353 | GEO
Project description:Postoperative neurocognitive disorder (PND) is one of the most common postoperative neurological complications in aged patients. In order to detect the differential expression profiles of genes caused by PND, a total of 26 18-month-old male C57BL/6 mice were randomly assigned to control group and PND group. Behavioral tests showed that mice in the PND group had impaired cognitive function compared with the control group. Three mice in each group were randomly selected to harvest the brain for analysis the expressions of circRNAs, miRNAs and mRNAs in the prefrontal cortex by next-generation sequencing (NGS) technology. Differentially expressed genes, including 1192 circRNAs, 27 miRNAs and 266 mRNAs were identified, and its accuracy was further confirmed by qRT-PCR.
2021-06-23 | GSE174412 | GEO