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GSE65682
Homo sapiens
802 Downloadable Samples
Affymetrix Human Genome U219 Array (hgu219)
Description
The 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.
Publication Title
A molecular biomarker to diagnose community-acquired pneumonia on intensive care unit admission.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 437 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Purpose: Severe late normal tissue damage limits radiotherapy treatment regimens. This study aims to validate -H2AX foci decay ratios and induced expression levels of DNA double strand break (DSB) repair genes, found in a retrospective study, as possible predictors for late radiation toxicity. Methods and Materials: Prospectively, decay ratios (initial/residual -H2AX foci numbers) and genome-wide expression profiles were examined in ex vivo irradiated lymphocytes of 198 prostate cancer patients. All patients were followed 2 years after radiotherapy, clinical characteristics were assembled and toxicity was recorded using the Common Terminology Criteria (CTCAE) v4.0. Results: No clinical factors were correlated with late radiation toxicity. Analysis of -H2AX foci uncovered a negative correlation between the foci decay ratio and toxicity grade. Significantly smaller decay ratios were found in grade3 compared to grade 0 patients (p=0.02), indicating less efficient DNA-DSB repair in radio-sensitive patients. Moreover, utilizing a foci decay ratio threshold determined in our previous retrospective study correctly classified 23 of the 28 grade3 patients (sensitivity, 82%) and 9 of the 14 grade 0 patients (specificity, 64%). Grade of toxicity also correlated with a reduced induction of the homologous recombination (HR) repair gene-set. The difference in average fold induction of the HR gene-set was most pronounced between grade 0 and grade3 patients (p=0.008). Conclusions: Reduced responsiveness of HR repair genes to irradiation and inefficient DSB repair correlate with an increased risk of late radiation toxicity. Using a decay ratio classifier, we could correctly classify 82% of the patients with grade3 toxicity. Additional studies are required to further optimize and validate the foci decay assay and to assess its predictive value for late radiation toxicity in patients prostate cancer
Publication Title
Prostate Cancer Patients with Late Radiation Toxicity Exhibit Reduced Expression of Genes Involved in DNA Double-Strand Break Repair and Homologous Recombination.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 103 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Consensus molecular subtypes of colorectal cancer are recapitulated in in vitro and in vivo models.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Cell line, Subject
View Samples- Homo sapiens
- 71 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Colorectal cancer (CRC) is a heterogeneous disease classified into four consensus molecular subtype (CMSs) with distinct biological and clinical features. This study aims to understand the value of patient-derived xenografts (PDXs) in relation to these CMSs. A total of 42 primary tumors, recurrences and metastases were used to develop PDXs. Detailed genetic analyses were performed on PDXs and corresponding patient tumors to determine relationship and PDX heterogeneity. Out of 42 tumors 22 (52%) showed successfully PDX engraftment, which was biased towards metastases and CMS1 and CMS4 tumors. Importantly, gene expression analysis revealed a clinical relevant association between an engraftment gene signature and prognosis for stage II patients. Moreover, this gene signature revealed an association between Src pathway activation and positive engraftment. Src pathway activity co-aligned with CMS4 and the levels of fibronectin in tumors and was confirmed by pSrc immunohistochemistry. From this analysis we further deduced that decreased cell cycle activity is a prognostic factor for successful engraftment and related to patient prognosis. However, this is not a general phenomenon, but subtype specific as decreased cell cycle activity was highly prognostic for recurrence-free survival within CMS2 but not in CMS1 and CMS4, while it showed an inverse correlation in CMS3. These data illustrate that CRC PDX establishment is biased toward CMS1 and CMS4, which impacts translation of results derived from pre-clinical studies using PDXs. Moreover, our analysis reveals subtype-specific features, pSrc in CMS4 and low Ki67 in CMS2, which provide novel avenues for therapy and diagnosis.
Publication Title
Capturing colorectal cancer inter-tumor heterogeneity in patient-derived xenograft (PDX) models.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 67 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Rhinovirus infections are the most common cause of asthma exacerbations. The complex responses by the airway epithelium to rhinovirus can be captured by gene expression profiling. We hypothesized that the upper and lower airway epithelium exhibit differential responses to double-stranded RNA (dsRNA), and that this is modulated by the presence of asthma and allergic rhinitis.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 52 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Colorectal cancer (CRC) is a highly heterogeneous disease both from a molecular and clinical perspective. Several distinct molecular entities, such as microsatellite instability (MSI), have been defined that make up biologically distinct subgroups with their own clinical course. Recent data indicated that CRC can be best segregated into four groups called Consensus Molecular Subtypes (CMS1-4), which each have a unique biology and gene expression pattern. In order to develop improved, subtype-specific therapies and to gain insight into the molecular wiring and origin of these subtypes, reliable models are needed. This study was designed to determine the heterogeneity and identify the presence of CMSs in a large panel of CRC cell lines, primary cultures and patient-derived xenografts (PDX). We provide a repository encompassing this heterogeneity and moreover describe that a large part of the models can be robustly assigned to one of the four CMSs, independent of the stromal contribution. We subsequently validate our CMS stratification by functional analysis which for instance shows mesenchymal enrichment in CMS4 and metabolic dysregulation in CMS3. Finally, we observe a clear difference in sensitivity to chemotherapy-induced apoptosis, specifically between CMS2 and CMS4. This relates to the in vivo efficacy of chemotherapy, which delays outgrowth of CMS2, but not CMS4 xenografts. This indicates that molecular subtypes are faithfully modelled in the CRC cell cultures and PDXs, representing tumour cell intrinsic and stable features. This repository provides researchers with a platform to study CRC using the existing heterogeneity.
Publication Title
Consensus molecular subtypes of colorectal cancer are recapitulated in in vitro and in vivo models.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Mus musculus, Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip, Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Multi-OMIC profiling of survival and metabolic signaling networks in cells subjected to photodynamic therapy.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
TGFβ signaling directs serrated adenomas to the mesenchymal colorectal cancer subtype.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
The link between upper and lower airways in patients with both asthma and allergic rhinitis is still poorly understood. As the biological complexity of these disorders can be captured by gene expression profiling we hypothesized that the clinical expression of rhinitis and/or asthma is related to differential gene expression between upper and lower airways epithelium.
Publication Title
The impact of allergic rhinitis and asthma on human nasal and bronchial epithelial gene expression.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 32 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Pneumonia accounts for more deaths than any other infectious disease worldwide. The intestinal microbiota has emerged as a key defense system by local support of mucosal immunity as well as proposed modulatory effects on systemic immunity. We here investigated the transcriptomes of whole-lungs and alveolar macrophages between untreated and antibiotic treated mice.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Treatment
View Samples