Ly6Chi monocytes massively infiltrate the CRC-tumors by virtue of their CCR2 expression and further mature into Ly6CloF4/80hi CD64hiMHCII+ TAM upon tumor progression. We demonstrated that TAM-deficient tumors display impaired tumor-growth via alternation of the ECM morphology, structure and composition. Using advanced high-resolution optical imaging to visualize the tumoral-ECM macromolecule network together with transcriptomic and proteomic approaches we unraveled that TAM play critical role in the deposition, linearization and cross-linking of collagenous ECM. Remarkably, we show that cues embedded in ECM by TAM-mediated remodeling activity promote tumor cell proliferation in vitro and orthotopic tumor development in vivo.
Tumor macrophages are pivotal constructors of tumor collagenous matrix.
Sex, Specimen part
View SamplesThe host response in critically ill patients with sepsis, septic shock remains poorly defined. Considerable research has been conducted to accurately distinguish patients with sepsis from those with non-infectious causes of disease. Technological innovations have positioned systems biology at the forefront of biomarker discovery. Analysis of the whole-blood leukocyte transcriptome enables the assessment of thousands of molecular signals beyond simply measuring several proteins in plasma, which for use as biomarkers is important since combinations of biomarkers likely provide more diagnostic accuracy than the measurement of single ones or a few. Evidence suggests that genome-wide transcriptional profiling of blood leukocytes can assist in differentiating between infection and non-infectious causes of severe disease. Of importance, RNA biomarkers have the potential advantage that they can be measured reliably in rapid quantitative reverse transcriptase polymerase chain reaction (qRT-PCR)-based point of care tests.
A molecular biomarker to diagnose community-acquired pneumonia on intensive care unit admission.
Sex, Age
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Whole blood transcriptome analysis in amyotrophic lateral sclerosis: A biomarker study.
Sex, Disease
View SamplesTranscriptome-wide analysis of whole blood gene expression profiles of ALS patients, gender- and age-matched controls and patients diagnosed with diseases mimicking ALS at a tertiary referral center for motor neuron diseases.
Whole blood transcriptome analysis in amyotrophic lateral sclerosis: A biomarker study.
Sex, Disease
View SamplesTranscriptome-wide analysis of whole blood gene expression profiles of ALS patients, gender- and age-matched controls and patients diagnosed with diseases mimicking ALS at a tertiary referral center for motor neuron diseases.
Whole blood transcriptome analysis in amyotrophic lateral sclerosis: A biomarker study.
Sex, Disease
View SamplesBackground: We got interested whether genes of airway basal cells are enriched in COPD.
BAL Cell Gene Expression Is Indicative of Outcome and Airway Basal Cell Involvement in Idiopathic Pulmonary Fibrosis.
Specimen part, Disease
View SamplesBackground: We got interested whether genes of airway basal cells are enriched in sarcoidosis.
BAL Cell Gene Expression Is Indicative of Outcome and Airway Basal Cell Involvement in Idiopathic Pulmonary Fibrosis.
Specimen part, Disease
View SamplesBackground: Systemic inflammation is a whole body reaction that can have an infection-positive (i.e. sepsis) or infection-negative origin. It is important to distinguish between septic and non-septic presentations early and reliably, because this has significant therapeutic implications for critically ill patients. We hypothesized that a molecular classifier based on a small number of RNAs expressed in peripheral blood could be discovered that would: 1) determine which patients with systemic inflammation had sepsis; 2) be robust across independent patient cohorts; 3) be insensitive to disease severity; and 4) provide diagnostic utility. The overall goal of this study was to identify and validate such a molecular classifier. Methods and Findings: We conducted an observational, non-interventional study of adult patients recruited from tertiary intensive care units (ICU). Biomarker discovery was conducted with an Australian cohort (n = 105) consisting of sepsis patients and post -surgical patients with infection-negative systemic inflammation. Using this cohort, a four-gene classifier consisting of a combination of CEACAM4, LAMP1, PLA2G7 and PLAC8 RNA biomarkers was identified. This classifier, designated SeptiCyte Lab, was externally validated using RT-qPCR and receiver operating characteristic (ROC) curve analysis in five cohorts (n = 345) from the Netherlands. Cohort 1 (n=59) consisted of unambiguous septic cases and infection-negative systemic inflammation controls; SeptiCyte Lab gave an area under curve (AUC) of 0.96 (95% CI: 0.91-1.00). ROC analysis of a more heterogeneous group of patients (Cohorts 2-5; 249 patients after excluding 37 patients with infection likelihood possible) gave an AUC of 0.89 (95% CI: 0.85-0.93). Disease severity, as measured by Sequential Organ Failure Assessment (SOFA) score or the Acute Physiology and Chronic Health Evaluation (APACHE) IV score, was not a significant confounding variable. The diagnostic utility o f SeptiCyte Lab was evaluated by comparison to various clinical and laboratory parameters that would be available to a clinician within 24 hours of ICU admission. SeptiCyte Lab was significantly better at differentiating sepsis from infection-negative systemic inflammation than all tested parameters, both singly and in various logistic combinations. SeptiCyte Lab more than halved the diagnostic error rate compared to PCT in all tested cohorts or cohort combinations. Conclusions: SeptiCyte Lab is a rapid molecular assay that may be clinically useful in the management of ICU patients with systemic inflammation.
A Molecular Host Response Assay to Discriminate Between Sepsis and Infection-Negative Systemic Inflammation in Critically Ill Patients: Discovery and Validation in Independent Cohorts.
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