The Validation set of the genomic nodal index (GNI) in 2014
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE234114 | GEO | 2023/06/09
REPOSITORIES: GEO
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Project description:A classifier was build on 82 training samples to differentiate between lymph node negative (N0) and lymph node metastasis (N+) head and neck squamous-cell carcinomas (HNSCC). The 102 predictor genes that resulted from this classifier where then validated against a independent validation set.
2005-01-09 | E-UMCU-11 | biostudies-arrayexpress
Project description:Lymph node involvement is the most important prognostic factor in breast cancer, but little is known about the underlying molecular changes. First, to identify a molecular signature associated with nodal metastasis, gene expression analysis was performed on a homogeneous group of 96 primary breast tumors, balanced for lymph node involvement. Each tumor was diagnosed as a poorly differentiated, estrogen positive, her2-neu negative invasive ductal cancer. (Affymetrix Human U133 Plus 2.0 microarray chips). A model, including 241 genes was built and validated on an internal and external dataset performed with Affymetrix technology. All samples used for validation had the same characteristics as the initial tumors. The area under the ROC curve (AUC) for the internal dataset was 0.646 and 0.651 for the external datasets. Thus, the molecular profile of a breast tumor reveals information about lymph node involvement, even in a homogeneous group of tumors. However, an AUC of 0.65 indicates only a weak correlation. Our model includes multiple kinases, apoptosis related and zinc ion binding genes. Pathway analysis using the Molecular Signatures Database revealed relevant gene sets (BAF57, Van 't Veer). Next, miRNA profiling was performed on 82/96 tumors using Human MiRNA microarray chips (Illumina). Eight miRNAs were significantly differentially expressed according to lymph node status at a significance level of 0.05, without correcting for multiple testing. The analysis of the inverse correlation between a miRNA and its computationally predicted targets point to general deregulation of the miRNA machinery potentially responsible for lymph node invasion. In conclusion, our results provide evidence that lymph node involvement in breast cancer is not a random process. Gene expression profiling: A training set of 96 patients and an independent internal dataset of 20 patients balanced for lymph node involvement was selected from the multidisciplinary breast centre database miRNA profiling not provided in this Series.
2011-02-04 | E-GEOD-23177 | biostudies-arrayexpress
Project description:We performed an expression profiling study of 168 primary breast tumors, lymph node metastases, and autopsy samples of primary breast tumours and metastases to liver, chest wall, lymph node, lung, and spleen, as well as positive and negative RNA controls, with technical replicates, to assess quality control methodology and probe-level reproducibility of the Illumina DASL microarray assay. The experiment included both Illumina DASL HumanRef-v3 and DASL HT-12; this series includes only the 120 HumanRef-v3 samples . This series includes 120 samples in total: 19 autopsy tissues of the chest wall, liver, lymph nodes, lung, spleen, liver, and breast, 5 negative controls, 6 positive controls, and 90 lymph node metastases.
2012-10-02 | E-GEOD-32489 | biostudies-arrayexpress
Project description:Lymph node involvement is the most important prognostic factor in breast cancer, but little is known about the underlying molecular changes. First, to identify a molecular signature associated with nodal metastasis, gene expression analysis was performed on a homogeneous group of 96 primary breast tumors, balanced for lymph node involvement. Each tumor was diagnosed as a poorly differentiated, estrogen positive, her2-neu negative invasive ductal cancer. (Affymetrix Human U133 Plus 2.0 microarray chips). A model, including 241 genes was built and validated on an internal and external dataset performed with Affymetrix technology. All samples used for validation had the same characteristics as the initial tumors. The area under the ROC curve (AUC) for the internal dataset was 0.646 and 0.651 for the external datasets. Thus, the molecular profile of a breast tumor reveals information about lymph node involvement, even in a homogeneous group of tumors. However, an AUC of 0.65 indicates only a weak correlation. Our model includes multiple kinases, apoptosis related and zinc ion binding genes. Pathway analysis using the Molecular Signatures Database revealed relevant gene sets (BAF57, Van 't Veer). Next, miRNA profiling was performed on 82/96 tumors using Human MiRNA microarray chips (Illumina). Eight miRNAs were significantly differentially expressed according to lymph node status at a significance level of 0.05, without correcting for multiple testing. The analysis of the inverse correlation between a miRNA and its computationally predicted targets point to general deregulation of the miRNA machinery potentially responsible for lymph node invasion. In conclusion, our results provide evidence that lymph node involvement in breast cancer is not a random process.
2011-02-04 | GSE23177 | GEO
Project description:The MAQC-II Project: A comprehensive study of common practices for the development and validation of microarray-based predictive models The second phase of the MicroArray Quality Control (MAQC-II) project evaluated common practices for developing and validating microarray-based models aimed at predicting toxicological and clinical endpoints. The purposes of the MAQC-II project were to survey approaches in genomic model development in an attempt to understand sources of variability in prediction performance, and to assess the influences of endpoint signal strength in data. Thirty-six teams developed classifiers for 13 diverse endpoints -- some easy, some difficult to predict, from six relatively large training data sets -- three preclinical (toxicogenomics) and three clinical. By providing the same data sets to many organizations for analysis, but not restricting their data analysis protocols (DAPs), the project made it possible to evaluate to what extent, if any, results depend on the team that performs the analysis. These analyses collectively produced >18,000 models that were challenged by independent and blinded validation sets generated for MAQC-II. The cross-validated performance estimates for models developed under good practices are predictive of the blinded validation performance. The achievable prediction performance is largely determined by the intrinsic predictability of the endpoint, and simple data analysis methods often perform as well as more complicated approaches. Multiple models of comparable performance can be developed for a given endpoint and the stability of gene lists correlates with endpoint predictability. Importantly, similar conclusions were reached when >12,000 new models were generated by swapping the original training and validation sets. Description of six data sets including 13 prediction endpoints: (Summarized in GSE16716_MAQC-II_Datasets_Overview.pdf attached as supplementary file. For more details, see the MAQC-II main paper and its references for individual dataset.) The MAQC-II predictive modeling was limited to binary classification problems; therefore, continuous endpoint values such as overall survival (OS) and event-free survival (EFS) times were dichotomized using a "milestone" cutoff of censor data. Prediction endpoints were chosen to span a wide range of prediction difficulty. Two endpoints, H (CPS1) and L (NEP_S), representing the gender of the patients, were used as positive control endpoints, since they are easily predictable by microarrays. Two other endpoints, I (CPS1) and M (NEP_R), representing randomly assigned class labels, were designed to serve as negative control endpoints, since they are not supposed to be predictable. Data analysis teams were not aware of the characteristics of endpoints H, I, L, and M until their swap prediction results had been submitted. If a data analysis protocol did not yield models to accurately predict endpoints H and L, or if a data analysis protocol claims to be able to yield models to accurately predict endpoints I and M, something must have gone wrong. The Hamner data set (endpoint A) was provided by The Hamner Institutes for Health Sciences (Research Triangle Park, NC, USA). The study objective was to apply microarray gene expression data from the lung of female B6C3F1 mice exposed to a 13-week treatment of chemicals to predict increased lung tumor incidence in the 2-year rodent cancer bioassays of the National Toxicology Program. If successful, the results may form the basis of a more efficient and economical approach for evaluating the carcinogenic activity of chemicals. Microarray analysis was performed using Affymetrix Mouse Genome 430 2.0 arrays on three to four mice per treatment group, and a total of 70 mice were analyzed and used as the MAQC-II's training set. Additional data from another set of 88 mice were collected later and provided as the MAQC-II's external validation set. The Iconix data set (endpoint B) was provided by Iconix Biosciences, Inc. (Mountain View, CA, USA). The study objective was to assess, upon short term exposure, hepatic tumor induction by non-genotoxic chemicals, since there are currently no accurate and well-validated short-term tests to identify non-genotoxic hepatic tumorigens, thus necessitating an expensive 2-year rodent bioassay before a risk assessment can begin. The training set consists of hepatic gene expression data from 216 male Sprague-Dawley rats treated for 5 days with one of 76 structurally and mechanistically diverse nongenotoxic hepatocarcinogens and non-hepatocarcinogens. The validation set consists of 201 male Sprague-Dawley rats treated for 5 days with one of 68 structurally and mechanistically diverse non-genotoxic hepatocarcinogens and non- hepatocarcinogens. Gene expression data were generated using the Amersham Codelink Uniset Rat 1 Bioarray (GE HealthCare, Piscataway, NJ). The separation of the training set and validation set was based on the time when the microarray data were collected; i.e., microarrays processed earlier in the study were used as training and those processed later were used as validation. The NIEHS data set (endpoint C) was provided by the National Institute of Environmental Health Sciences (NIEHS) of the National Institutes of Health (Research Triangle Park, NC, USA). The study objective was to use microarray gene expression data acquired from the liver of rats exposed to hepatotoxicants to build classifiers for prediction of liver necrosis. The gene expression "compendium" data set was collected from 418 rats exposed to one of eight compounds (1,2- dichlorobenzene, 1,4-dichlorobenzene, bromobenzene, monocrotaline, N-nitrosomorpholine, thioacetamide, galactosamine, and diquat dibromide). All eight compounds were studied using standardized procedures, i.e. a common array platform (Affymetrix Rat 230 2.0 microarray), experimental procedures and data retrieving and analysis processes. Briefly, for each compound, four to six male, 12 week old F344 rats were exposed to a low dose, mid dose(s) and a high dose of the toxicant and sacrificed at 6, 24 and 48 hrs later. At necropsy, liver was harvested for RNA extraction, histopathology, and clinical chemistry assessments. The human breast cancer (BR) data set (endpoints D and E) was contributed by the University of Texas M. D. Anderson Cancer Center (MDACC, Houston, TX, USA). Gene expression data from 230 stage I-III breast cancers were generated from fine needle aspiration specimens of newly diagnosed breast cancers before any therapy. The biopsy specimens were collected sequentially during a prospective pharmacogenomic marker discovery study between 2000 and 2008. These specimens represent 70-90% pure neoplastic cells with minimal stromal contamination. Patients received 6 months of preoperative (neoadjuvant) chemotherapy including paclitaxel, 5-fluorouracil, cyclophosphamide and doxorubicin followed by surgical resection of the cancer. Response to preoperative chemotherapy was categorized as a pathological complete response (pCR = no residual invasive cancer in the breast or lymph nodes) or residual invasive cancer (RD), and used as endpoint D for prediction. Endpoint E is the clinical estrogen-receptor status as established by immunohistochemistry. RNA extraction and gene expression profiling were performed in multiple batches over time using Affymetrix U133A microarrays. Genomic analysis of a subset of this sequentially accrued patient population were reported previously. For each endpoint, the first 130 cases were used as a training set and the next 100 cases were used as an independent validation set. The multiple myeloma (MM) data set (endpoints F, G, H, and I) was contributed by the Myeloma Institute for Research and Therapy at the University of Arkansas for Medical Sciences (UAMS, Little Rock, AR, USA). Gene expression profiling of highly purified bone marrow plasma cells was performed in newly diagnosed patients with MM. The training set consisted of 340 cases enrolled on total therapy 2 (TT2) and the validation set comprised 214 patients enrolled in total therapy 3 (TT3). Plasma cells were enriched by anti-CD138 immunomagnetic bead selection of mononuclear cell fractions of bone marrow aspirates in a central laboratory. All samples applied to the microarray contained more than 85% plasma cells as determined by 2-color flow cytometry (CD38+ and CD45-/dim) performed after selection. Dichotomized overall survival (OS) and eventfree survival (EFS) were determined based on a two-year milestone cutoff. A gene expression model of high-risk multiple myeloma was developed and validated by the data provider and later on validated in three additional independent data sets. The neuroblastoma (NB) data set (endpoints J, K, L, and M) was contributed by the Children's Hospital of the University of Cologne, Germany. Tumor samples were checked by a pathologist prior to RNA isolation; only samples with =60% tumor content were utilized and total RNA was isolated from ~50mg of snap-frozen neuroblastoma tissue obtained before chemotherapeutic treatment. First, 502 pre-existing 11K Agilent dye-flipped, dual-color replicate profiles for 251 patients were provided. Of these, profiles of 246 neuroblastoma samples passed an independent MAQC-II quality assessment by majority decision and formed the MAQC-II training data set. Subsequently, 514 dyeflipped dual-color 11K replicate profiles for 256 independent neuroblastoma tumor samples were generated and profiles for 253 samples were selected to form the MAQC-II validation set. Of note, for one patient of the validation set, two different tumor samples were analyzed utilizing both versions of the 2x11K microarray (see below). All dual-color gene-expression of the MAQC-II training set were generated using a customized 2x11K neuroblastoma-related microarray. Furthermore, 20 patients of the MAQC-II validation set were also profiled utilizing this microarray. Dual-color profiles of the remaining patients of the MAQC-II validation set were performed using a slightly revised version of the 2x11K microarray. This version V2.0 of the array comprised 200 novel oligonucleotide probes whereas 100 oligonucleotide probes of the original design were removed due to consistent low expression values (near background) observed in the training set profiles. These minor modifications of the microarray design resulted in a total of 9,986 probes present on both versions of the 2x11K microarray. The experimental protocol did not differ between both sets and gene-expression profiles were performed as described. Furthermore, single-color geneexpression profiles were generated for 478/499 neuroblastoma samples of the MAQC-II dual-color training and validation sets (training set 244/246; validation set 234/253). For the remaining 21 samples no single-color data were available, due to either shortage of tumor material of these patients (n=15), poor experimental quality of the generated single-color profiles (n=5), or correlation of one single-color profile to two different dual-color profiles for the one patient profiled with both versions of the 2x11K microarrays (n=1). Single-color gene-expression profiles were generated using customized 4x44K oligonucleotide microarrays produced by Agilent Technologies (Palo Alto, CA, USA). These 4x44K microarrays included all probes represented by Agilent's Whole Human Genome Oligo Microarray and all probes of the version V2.0 of the 2x11K customized microarray that were not present in the former probe set. Labeling and hybridization was performed following the manufacturer's protocol as described. This SuperSeries is composed of the following subset Series: GSE20194: MAQC-II Project: human breast cancer (BR) data set Additional subset Series will be submitted later Refer to individual Series
2010-02-04 | E-GEOD-16716 | biostudies-arrayexpress
Project description:Lymph node metastases (LNM) and primary tumour samples were analysed using desorption electrospray ionisation mass spectrometry imaging (DESI MSI). Current assessment of LNM depends on subjective histopathological assessment, whereas analysis by DESI MSI permits an entirely objective assessment. The mass spectral data revealed specific lipidomic patterns across samples, which were shown to correspond to the immunohistochemical image. Statistical prediction of LNM samples was performed using the esophageal adenocarcinoma samples with sensitivity and specificity of 89.5% and 100%, respectively.
2017-01-10 | MTBLS385 | MetaboLights
Project description:We performed an expression profiling study of 168 primary breast tumors, lymph node metastases, and autopsy samples of primary breast tumours and metastases to liver, chest wall, lymph node, lung, and spleen, as well as positive and negative RNA controls, with technical replicates, to assess quality control methodology and probe-level reproducibility of the Illumina DASL microarray assay. The experiment included both Illumina DASL HumanRef-v3 and DASL HT-12; this series includes only the 120 HumanRef-v3 samples .
2012-10-02 | GSE32489 | GEO
Project description:Validation of a previously established gene expression profile for detection of lymph node metastasis (ArrayExpress E-UMCU-11).
2012-10-10 | GSE30788 | GEO
Project description:In this paper we show for the first time a metabolomic-based biomarker discovery using HRMS applied to plasma of NB patients and its validation on a second independent cohort of patients using a different analytical method.
2021-10-15 | ST002238 | MetabolomicsWorkbench
Project description:Background Breast cancer patients who present in the early stage of disease are affected by metastasis to the axillary group of lymph nodes. The first among this group that is affected is called as sentinel lymph node, and metastasis to this lymph node is crucial for the staging of cancer and the quality of surgical intervention. Sentinel Lymph Node Biopsy (SLNB) that is currently used to assess lymph node metastasis is neither sensitive, nor specific, is time-consuming, thereby necessitating the identification of novel biomarkers that can flag sentinel lymph node metastasis. Methods Breast cancer patients were screened, and those with early stage were recruited in the study. Surgical resection of the breast was followed by identification of sentinel lymph nodes by methylene fluorescent technique. Histo-pathology of fresh frozen section biopsy was used as the gold standard to assign the clinical phenotypes of metastatic (SLNM+) and non-metastatic sentinel lymph nodes (SLNM-). Discovery phase of the experiment included isobaric Tags for Relative and Absolute Quantitation (iTRAQ) technique comprising of six comparative experiments coupled with mass spectrometric analysis on Orbitrap Fusion to identify differentially expressed proteins on Proteome Discoverer 2.4. Functional enrichment and pathway analyses of differentially regulated genes was carried out in DAVID functional annotation tool. Validation was done by ELISA and protein concentrations were used to estimate the ROC for computing diagnostic parameters. Results Based on MS/MS spectra there were 2396 unique protein groups and 81 differentially expressed proteins comparing SLNB + and SLNB -. Nineteen proteins up-regulated, and eight proteins that were down regulated in SLNB+ as compared to SLNB-. Bioinformatic analysis showed the implication of extra cellular matrix proteins and ECM-receptor interaction pathways to be implicated in lymph node metastasis. ELISA confirmed the up-regulation of caveolin 1, collagen α-1, desmin, fibrillin-1, and microfibrillar associated glycoprotein 4 in metastatic, as compared to non-metastatic lymph nodes. These proteins are known to be integral in tumorogenesis, cell proliferation, invasion, cell survival and anti-apoptosis. These proteins have 80%-100%, of sensitivity and specificity to differentiate the two clinical phenotypes. Conclusion Identified extra cellular matrix protein biomarkers have requisite diagnostic parameters to be developed as a translational tool to assess the status of sentinel lymph nodes during mastectomy procedure to guide surgical therapy of axillary lymph nodes in early breast oncology.
2022-05-01 | PXD027668 | Pride