Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide. The oxygen-sensitive Hypoxia Inducible Factor (HIF) transcriptional regulators HIF-1 and HIF-2 are overexpressed in many human NSCLCs, and constitutive HIF-2 activity can promote murine lung tumor progression, suggesting that HIF proteins may be effective NSCLC therapeutic targets. To investigate the consequences of inhibiting HIF activity in lung cancers, we deleted Hif-1 or Hif-2 in an established KrasG12D-driven murine NSCLC model. Deletion of Hif-1 had no obvious effect on tumor growth, whereas Hif-2 deletion resulted in an unexpected increase in tumor burden that correlated with reduced expression of the candidate tumor suppressor gene Scgb3a1 (HIN-1).
HIF-2alpha deletion promotes Kras-driven lung tumor development.
No sample metadata fields
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 SamplesWe report a 29-gene diagnostic signature, which distinguishes individuals with NSCLC from controls with non-malignant lung disease with 91% Sensitivity, 79% Specificity and a ROC AUC of 92%. Accuracy on an independent set of 18 NSCLC samples from the same location was 79%. Samples from an independent location including 12 stage 1 NSCLC and 15 controls, achieved an accuracy of 74%. A study of 18 paired samples taken pre and post surgery shows that the PBMC associated cancer signature is significantly reduced after tumor removal, supporting the hypothesis that the signature detected in pre-surgery samples is a response to the presence of the tumor.
Gene expression profiles in peripheral blood mononuclear cells can distinguish patients with non-small cell lung cancer from patients with nonmalignant lung disease.
Sex, Age, Race
View SamplesPI3K/AKT pathway plays one of pivotal roles in breast cancer development and maintenance. PIK3CA, coding PIK3 catalytic subunit, is the oncogene which shows the high frequency of gain-of-function mutations leading to the PI3K/AKT pathway activation in breast cancer. In particular in the ER-positive breast tumors PIK3CA mutations have been observed in 30% to 40%. However, genes expressed in connection to the pathway activation in breast tumorigenesis remain largely unknown.
Gene expression profiling reveals new aspects of PIK3CA mutation in ERalpha-positive breast cancer: major implication of the Wnt signaling pathway.
Sex, Age, Specimen part
View SamplesMorphogenesis of the mammary gland relies on the precise developmental control of morphological elements including TEBs, ducts and lobules. In the peripubertal mammary gland, rising levels of ovarian hormones control this development through a tightly controlled genetic program where specific sets of genes are up-regulated.
In utero and lactational exposure to vinclozolin and genistein induces genomic changes in the rat mammary gland.
Specimen part, Treatment
View SamplesVascular endothelial growth factor is a multifunctional cytokine playing important roles in angiogenesis, tumor progression and metastasis. Alternative splicing results in the production of several different isoforms of VEGF. We have previously generated human breast cancer cells overexpressing VEGF165 or VEGF189 isoforms (referred to as the V165 and V189 clones, respectively) and showed that VEGF189-transfected cells were less tumorigenic. In this study, we used bioluminescence imaging to analyze the metastasis capacity of breast cancer cell lines (MDA-MB-321) overexpressing VEGF isoforms in nude mice. V165, V189 and control cV clones were transfected with a luciferase plasmid to generate bioluminescent clones (the V165-B, V189-B and cV clones, respectively). These clones were then injected into the left heart ventricle of nude mice.
MDA-MB-231 breast cancer cells overexpressing single VEGF isoforms display distinct colonisation characteristics.
No sample metadata fields
View SamplesDifferentially expressed genes between 171 human soft tissue sarcomas with complex genomics
From PTEN loss of expression to RICTOR role in smooth muscle differentiation: complex involvement of the mTOR pathway in leiomyosarcomas and pleomorphic sarcomas.
Sex, Specimen part, Cell line
View SamplesIdentification of predictive markers of response to treatment is a major objective in breast cancer. A major problem in clinical sampling is the variability of RNA templates, requiring accurate management of tumour material and subsequent analyses for future translation in clinical practice. Our aim was to establish the feasibility and reliability of high throughput RNA analysis in a prospective trial.
Importance of pre-analytical steps for transcriptome and RT-qPCR analyses in the context of the phase II randomised multicentre trial REMAGUS02 of neoadjuvant chemotherapy in breast cancer patients.
Specimen part, Disease stage
View SamplesAcquired resistance to endocrine therapy occurs with high frequency in patients with luminal breast cancer (LBC). We report here the establishment of four patient-derived xenograft models of LBC with acquired resistance in vivo to tamoxifen and estrogen deprivation.
Acquired resistance to endocrine treatments is associated with tumor-specific molecular changes in patient-derived luminal breast cancer xenografts.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Medullary Breast Carcinoma, a Triple-Negative Breast Cancer Associated with BCLG Overexpression.
Disease, Disease stage
View Samples