Preterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, precise phenotyping of the preterm birth is hampered by the imprecise definition of the clinical phenotype and complexity of the molecular phenotype due to multiple pregnancy tissue types and molecular processes that may contribute to the preterm birth. The studys aim was to comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor using precisely phenotyped samples. Expression profiles of 73 genes and non-coding RNA sequences uniquely identified the four groups of patients: delivering preterm with (PL) and without labor (PNL), term with (TL) and without labor (TNL). The largest differences in gene expression among the four groups occurred in decidua, chorion and amnion. The gene expression profiles showed suppression of chemokines expression in TNL, withdrawal of this suppression in TL, activation of multiple pathways of inflammation in PL, and an immune rejection profile in PNL. The genes constituting expression signatures showed over-representation of three putative regulatory elements in their 5 and 3UTR regions. The results suggest that pregnancy is maintained by downregulation of chemokines at the maternal-fetal interface. Withdrawal of this downregulation results in the term birth and its overriding by the activation of multiple pathways of the immune system in the preterm birth. Complications of the pregnancy associated with impairment of placental function, which necessitated premature delivery of the fetus in the absence of labor, show gene expression patterns associated with immune rejection.
No associated publication
Sex, Specimen part, Subject
View SamplesMolecular prognostic assays, such as Oncotype DX, are increasingly incorporated into the management of patients with invasive breast carcinoma. BreastPRS is a new molecular assay developed and validated from a meta-analysis of publically available genomic datasets. We applied the assay to matched fresh-frozen (FF) and formalin-fixed paraffin embedded (FFPE) tumor samples to translate the assay to FFPE. A linear relationship of the BreastPRS prognostic score was observed between tissue preservation formats. BreastPRS recurrence scores were compared with Oncotype DX recurrence scores from 246 patients with invasive breast carcinoma and known Oncotype DX results. Using this series, a 120-gene linear discriminant algorithm (LDA) was trained to predict Oncotype DX risk groups and then applied to series of untreated, node-negative, estrogen receptor (ER) positive patients from previously published studies with known clinical outcomes. Correlation of recurrence score and risk group between Oncotype DX and BreastPRS was statistically significant (P<0.0001). 59 of 260 (23%) patients from four previously published studies were classified as intermediate-risk when the 120-gene LDA was applied. BreastPRS reclassified the 59 patients into binary risk groups (high vs. low-risk). 23 (39%) patients were classified as low-risk 36 (61%) as high-risk [P=0.029, HR: 3.64, 95% CI: 1.40 to 9.50]. At 10 years from diagnosis, the low-risk group had a 90% recurrence-free survival (RFS) rate, compared to 60% for the high-risk group. BreastPRS recurrence score is comparable to Oncotype DX and can reclassify Oncotype DX intermediate-risk patients into two groups with significant differences in RFS. Further studies are needed to validate these findings.
BreastPRS is a gene expression assay that stratifies intermediate-risk Oncotype DX patients into high- or low-risk for disease recurrence.
Disease stage
View SamplesOxidative stress is a common phenomenon and is linked to a wide range of diseases and pathological processes. Tissue-specific variation in redox signaling and cellular responses to oxidative stress may be associated with vulnerability to toxic agents and carcinogenic exposures. In order to provide a basis for tissue-specific difference, we examined the tissue-specific transcriptional features of 101 oxidative stress-associated genes in 10 different tissues and organs of healthy mice under physiological conditions.
Tissue-Specific Profiling of Oxidative Stress-Associated Transcriptome in a Healthy Mouse Model.
Sex
View SamplesBACKGROUND: In patients with suspicious pulmonary lesions, bronchoscopy is frequently non-diagnostic. This often results in additional invasive testing, including surgical biopsy, although many patients have benign disease. We sought to validate an airway gene-expression classifier for lung cancer in patients undergoing diagnostic bronchoscopy. METHODS: Two multicenter prospective studies (AEGIS 1 and 2) enrolled 1357 current or former smokers undergoing bronchoscopy for suspected lung cancer. Bronchial epithelial cells were collected from normal appearing mucosa in the mainstem bronchus during bronchoscopy. Patients without a definitive diagnosis from bronchoscopy were followed for 12 months. A gene-expression classifier was used to assess the risk of lung cancer, and its performance was evaluated. RESULTS: A total of 298 patients from AEGIS 1 and 341 from AEGIS 2 met criteria for analysis. Bronchoscopy was non-diagnostic for cancer in 272 of 639 patients (43%; 95%CI, 39-46%). The gene expression classifier correctly identified 431 of 487 patients with cancer (89% sensitivity; 95%CI, 85-91%), and 72 of 152 patients without cancer (47% specificity; 95%CI, 40-55%). The combination of the classifier and bronchoscopy had a sensitivity of 97% (95%CI, 95-98%), which was independent of size, location, stage, and histological subtype of lung cancer. In patients with an intermediate pre-test risk (10-60%) of lung cancer, the NPV of the classifier was 91% (95%CI 75-98%). CONCLUSIONS: In patients with an intermediate risk of lung cancer and a non-diagnostic bronchoscopy, a gene-expression classification of low-risk warrants consideration of a more conservative diagnostic approach that could reduce unnecessary invasive testing in patients with benign disease.
A Bronchial Genomic Classifier for the Diagnostic Evaluation of Lung Cancer.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Gene expression profiling reveals epithelial mesenchymal transition (EMT) genes can selectively differentiate eribulin sensitive breast cancer cells.
Specimen part, Cell line
View SamplesThe systematic characterization of somatic mutations in cancer genomes is essential for understanding the disease and for developing targeted therapeutics. Here we report the identification of 2,576 somatic mutations across approximately 1,800 megabases of DNA representing 1,507 coding genes from 441 tumours comprising breast, lung, ovarian and prostate cancer types and subtypes. Additionally, 373 tumors were assayed for copy number alterations via Agilent 244A CGH arrays and 153 breast, lung, and colon samples were assayed for mRNA abundance with Affymetrix HuEx1 Exon Arrays.
Diverse somatic mutation patterns and pathway alterations in human cancers.
Specimen part
View SamplesGastric cancer, a leading cause of cancer related deaths, is a heterogeneous disease, with little consensus on molecular subclasses and their clinical relevance. We describe four molecular subtypes linked with distinct patterns of molecular alterations, disease progression and prognosis viz. a) Microsatellite Instable: hypermutated intestinal subtype tumors occurring in antrum, best overall prognosis, lower frequency of recurrence (22%), with liver metastasis in 23% of recurred cases b) Mesenchymal-like: diffuse tumors with worst prognosis, a tendency to occur at an earlier age and highest recurrence (63%) with peritoneal seeding in 64% of recurred cases, low frequency of molecular alterations c) TP53-inactive with TP53 loss, presence of focal amplifications and chromosomal instability d) TP53-active marked by EBV infection and PIK3CA mutations. The key molecular mechanisms and associated survival patterns are validated in multiple independent cohorts, to provide a consistent and unified framework for further preclinical and clinical research.
Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
No associated publication
Specimen part, Subject
View SamplesThis study is designed to compare and contrast the temporal and spatial changes in bone formation rates and transcriptional profiles in cortical and cancellous bone cell populations enriched by laser capture microdissection (LCM) in ovariectomized rats administered Scl-Ab by subcutaneous injection for up to 26 consecutive weeks, followed by a recovery period of up to 18 weeks.
Time-dependent cellular and transcriptional changes in the osteoblast lineage associated with sclerostin antibody treatment in ovariectomized rats.
Sex, Specimen part, Time
View SamplesEribulin mesylate is a synthetic macrocyclic ketone analog of the marine sponge natural product halichondrin B. Eribulin is a mechanistically unique inhibitor of microtubule dynamics, leading to inhibition of microtubule growth in the absence of effects on microtubule shortening at microtubule plus ends, and formation of nonproductive tubulin aggregates. In this study, we investigated whether selective signal pathways were associated with eribulin activity compared to paclitaxel, which stabilizes microtubules, based on gene expression profiling of cell line panels of breast, endometrial, and ovarian cancer in vitro.
Gene expression profiling reveals epithelial mesenchymal transition (EMT) genes can selectively differentiate eribulin sensitive breast cancer cells.
Specimen part, Cell line
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