Systematic analysis of clinical relevance and molecular characterization of m6A in COVID-19 patients.
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SUBMITTER: An S
PROVIDER: S-EPMC8730760 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Clinical and molecular characterization by Whole Exome Sequencing (WES) is reported in 35 COVID-19 patients attending the University Hospital in Siena, Italy, from April 7 to May 7, 2020. Eighty percent of patients required respiratory assistance, half of them being on mechanical ventilation. Fiftyone percent had hepatic involvement and hyposmia was ascertained in 3 patients. Searching for common genes by collapsing methods against 150 WES of controls of the Italian population failed to give straightforward statistically significant results with the exception of two genes. This result is not unexpected since we are facing the most challenging common disorder triggered by environmental factors with a strong underlying heritability (50%). The lesson learned from Autism-Spectrum-Disorders prompted us to re-analyse the cohort treating each patient as an independent case, following a Mendelian-like model. We identified for each patient an average of 2.5 pathogenic mutations involved in virus infection susceptibility and pinpointing to one or more rare disorder(s). To our knowledge, this is the first report on WES and COVID-19. Our results suggest a combined model for COVID-19 susceptibility with a number of common susceptibility genes which represent the favorite background in which additional host private mutations may determine disease progression.
| S-EPMC7673557 | biostudies-literature
Project description:Immunosuppression caused by cancer itself and cytotoxic treatment may pose a challenge to coronavirus disease 2019 (COVID-19) patients with hematological malignancies. Here, we use multidimensional flow cytometry (MFC) to analyze immune profiles in peripheral blood samples of 515 COVID-19 patients at presentation. In 14 cases, deep immunophenotyping of B- and T-cells was performed and six myeloid- and dendritic-cell subsets were FACSorted for transcriptome analysis using RNAseq. Of the 515 patients, 15 and 10 had solid and hematological tumors, respectively. Those with hematological cancer showed significantly higher rates of intensive care (50%) and death (30%) from COVID-19 vs cases with solid cancer and no tumor. Patients with hematological malignancies displayed altered immune profiles with significantly decreased absolute numbers of several subsets of myeloid and lymphoid cells. Myeloid- and dendritic-cell types from hematological cases showed differentially expression of genes coding transcription factors, toll-like receptors and proinflammatory interleukin receptors implicated in response to coronaviruses. The relative distribution of the B-cell compartment was notoriously altered in COVID-19 patients with hematological cancer, and progressively lower numbers of B- and T-cell subsets were observed in deceased cases. Altogether, our results suggest an association between impaired immune responses and poorer outcomes in COVID-19 patients with hematological malignancies.
2020-12-31 | GSE153610 | GEO
Project description:The methylation of N6 adenosine (m6A) plays a critical role in diverse biological processes. However, knowledge regarding the reconstitution of m6A across cancer types is still lacking. Here, we systematically analyzed the molecular alterations and clinical relevance of m6A regulators across >?10,000 subjects representing 33 cancer types. We found that there are widespread genetic alterations to m6A regulators, and that their expression levels are significantly correlated with the activity of cancer hallmark-related pathways. Moreover, m6A regulators were found to be potentially useful for prognostic stratification, and we identified IGF2BP3 as a potential oncogene across multiple cancer types. Our results provide a valuable resource that will guide both mechanistic and therapeutic analyses of the role of m6A regulators in cancer.
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Project description:Digestive system tumors, which mainly include esophagus, stomach, colorectum, liver, pancreas, bile duct, and some other tumors, often have a poor prognosis. N6-methyladenosine (m6A) has critical functions in development and tumorigenesis and may help improve the molecular mechanisms of digestive system tumors. However, current understanding of the reconstitution of m6A in digestive system tumors is far from comprehensive. Herein, this study systematically analyzed multi-layered genomic characteristics and clinical relevance of m6A regulators in 1906 patients involving seven digestive system tumor types. We discovered that m6A regulators showed extensive genetic changes and highly consistent expression regulation. The m6A expression was closely related to the activity of cancer pathways. At the same time, we also identified m6A regulators significantly related to the common cancer pathways of digestive system tumors and specific cancer pathways of digestive tract and digestive glands. These cancer pathways may explain the prognostic differences of patients with digestive tract tumors. In addition, m6A regulators demonstrated strong potential in prognostic stratification and drug development, especially in multiple research cohorts on pancreatic cancer, pointing to a strong prognostic stratification capability of m6A regulators. Finally, a m6A scoring model significantly related to highly active ubiquitin-mediated proteolysis, mismatch repair, cell cycle, ebasal transcription factors was constructed and had a strong prognostic stratification ability in digestive gland tumors. The score showed a significant negative correlation with the tumor immune microenvironment. This study demonstrated that the similarities and difference of the action mechanism m6A regulators in the digestive tract and digestive gland tumor progression could guide potential drug development.
| S-EPMC8474987 | biostudies-literature
Project description:BackgroundDelirium prevalence increases with age and is associated with poor outcomes. We aimed to investigate the prevalence and risk factors for delirium in older patients hospitalized with COVID-19, as well as its association with length of stay and mortality.MethodThis was a retrospective study of patients aged 65 years and older hospitalized with COVID-19. Data were collected from computerized medical records and all patients had delirium assessment at admission. Risk factors for delirium as well as the outcomes mentioned above were studied by 2-group comparison, logistic regression, and Cox proportional hazard models.ResultsOf a total of 235 Caucasian patients, 48 (20.4%) presented with delirium, which was hypoactive in 41.6% of cases, and hyperactive and mixed in 35.4% and 23.0%, respectively. Patients with cognitive impairment had a nearly 4 times higher risk of developing delirium compared to patients who were cognitively normal before SARS-CoV-2 infection (odds ratio 3.7; 95% CI: 1.7-7.9, p = .001). The presence of delirium did not modify the time from symptoms' onset to hospitalization or the length of stay in acute care, but it was associated with an increased risk of dying (hazard ratio 2.1; 95% CI: 1.2-3.7, p = .0113).ConclusionDelirium was a prevalent condition in older people admitted with COVID-19 and preexisting cognitive impairment was its main risk factor. Delirium was associated with higher in-hospital mortality. These results highlight the importance of early recognition of delirium especially when premorbid cognitive comorbidities are present.
| S-EPMC7929187 | biostudies-literature
Project description: Not available
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Project description: Not available
| S-BSST416 | biostudies-other
Project description:Background: Aldehyde dehydrogenase 2 (ALDH2) is well-known to be a key enzyme in alcohol metabolism. However, a comprehensive understanding of ALDH2 across human cancers is lacking. Methods: A systematic and comprehensive analysis of the molecular alterations and clinical relevance for ALDH2 in more than 10,000 samples from 33 cancer types was performed. qRT-PCR was performed on 60 cancer and 60 paired nontumor tissues. Results: It was observed that ALDH2 was generally downregulated in most cancers, which was mainly driven by DNA hypermethylation rather than mutations or copy number variations. Besides, ALDH2 was closely related to the inhibition and activation of tumor pathways and a variety of potential targeted agents had been discovered in our research. Last but not least, ALDH2 had the best prediction efficacy in assessing immunotherapeutic response compared with PD-L1, PD-1, CTLA4, CD8, and tumor mutation burden (TMB) in cutaneous melanoma. According to the analysis of large-scale public data and 60 pairs of clinical cancer samples, we found the downregulation of ALDH2 expression tends to suggest the malignant phenotypes and adverse prognosis, which might enhance the precise diagnosis and timely intervention of cancer patients. Conclusion: This study advanced the understanding of ALDH2 across cancers, and provided important insight into chemotherapy, immunotherapy and prognosis of patients with cancer.
| S-EPMC8792945 | biostudies-literature
Project description:BackgroundStroke in the course of coronavirus disease (COVID-19) has been shown to be associated with more severe respiratory symptoms and higher mortality, but little knowledge in this regard exists on older populations. We aimed to investigate the incidence, characteristics, and prognosis of acute stroke in geriatric patients hospitalized with COVID-19.MethodsA monocentric cross-sectional retrospective study of 265 older patients hospitalized with COVID-19 on acute geriatric wards. 11/265 presented a stroke episode during hospitalization. Mortality rates and two-group comparisons (stroke vs non-stroke patients) were calculated and significant variables added in logistic regression models to investigate stroke risk factors.ResultsCombined ischemic and hemorrhagic stroke incidence was 4.15%. 72.7% of events occurred during acute care. Strokes presented with altered state of consciousness and/or delirium in 81.8%, followed by a focal neurological deficit in 45.5%. Ischemic stroke was more frequently unilateral (88.8%) and localized in the middle cerebral artery territory (55.5%). Smoking and a history of previous stroke increased by more than seven (OR 7.44; 95% CI 1.75-31.64; p = 0.007) and five times (OR 5.19; 95% CI 1.50-17.92; p = 0.009), respectively, the risk of stroke. Each additional point in body mass index (BMI) reduced the risk of stroke by 14% (OR 0.86; 95% CI 0.74-0.98; p = 0.03). In-hospital mortality (32.1% vs. 27.3%; p > 0.999) and institutionalization at discharge (36.4% vs. 21.1%; p = 0.258) were similar between patients with and without stroke.ConclusionIncident stroke complicating COVID-19 in old patients was associated with active smoking, previous history of stroke, and low BMI. Acute stroke did not influence early mortality or institutionalization rate at discharge.
| S-EPMC7807227 | biostudies-literature
Project description:Pituitary adenomas (PA) are amongst the most prevalent intracranial tumors, causing complications by hormonal overproduction or deficiency and tumor mass effects, with 95% of cases occurring sporadically. Associated germline mutations (AIP, MEN1, CDKN1B, PRKAR1A, SDHx) and Xq26.3 microduplications are increasingly identified, but the clinical consequences in sporadic PA remain unclear. This systematic review evaluates predictors of a genetic cause of sporadic PA and the consequences for treatment outcome. We undertook a sensitive MEDLINE/Pubmed, EMBASE, and Web of Science search with critical appraisal of identified studies. Thirty-seven studies on predictors of mutations and 10 studies on the influence on treatment outcome were included. AIP and MEN1 mutations were associated with young age of PA diagnosis. AIP mutations were also associated with gigantism and macroadenomas at time of diagnosis. Xq26.3 microduplications were associated with PA below the age of five. AIP and MEN1 mutation analysis is therefore recommended in young patients (?30 years). AIP mutation analysis is specifically recommended for patients with PA induced gigantism and macroadenoma. Screening for Xq26.3 microduplications is advisable in children below the age of five with increased growth velocity due to PA. There is no evidence supporting mutation analysis of other genes in sporadic PA. MEN1 mutation related prolactinoma respond well to dopamine agonists while AIP mutation associated somatotroph and lactotroph adenoma are frequently resistant to medical treatment. In patients harboring an Xq26.3 microduplication treatment is challenging, although outcome is not different from other patients with PA induced gigantism. Effective use of genetic analysis may lead to early disease identification, while knowledge of the impact of germline mutations on susceptibility to various treatment modalities helps to determine therapeutic strategies, possibly lowering disease morbidity.
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