Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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CaArray_jacob-00182: Gene expression-based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study

ABSTRACT: Here we report a large, training*testing, multi-site, blinded validation study to characterize the performance of several prognostic models based on gene expression for 442 lung adenocarcinomas. The hypotheses proposed examined whether microarray measurements of gene expression either alone or combined with basic clinical covariates (stage, age, sex) could be used to predict overall survival in lung cancer subjects. Several models examined produced risk scores that substantially correlated with actual subject outcome. Most methods performed better with clinical data, supporting the combined use of clinical and molecular information when building prognostic models for early-stage lung cancer. This study also provides the largest available set of microarray data with extensive pathological and clinical annotation for lung adenocarcinomas. jacob-00182 Assay Type: Gene Expression Provider: Affymetrix Array Designs: HG-U133A Organism: Homo sapiens (ncbitax) Material Types: cell, synthetic_RNA, organism_part, whole_organism, total_RNA Disease States: Lung Adenocarcinoma

ORGANISM(S): Homo sapiens

SUBMITTER: Mervi Heiskanen

PROVIDER: E-GEOD-68465 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Gene expression-based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study.

Shedden Kerby K Taylor Jeremy M G JM Enkemann Steven A SA Tsao Ming-Sound MS Yeatman Timothy J TJ Gerald William L WL Eschrich Steven S Jurisica Igor I Giordano Thomas J TJ Misek David E DE Chang Andrew C AC Zhu Chang Qi CQ Strumpf Daniel D Hanash Samir S Shepherd Frances A FA Ding Keyue K Seymour Lesley L Naoki Katsuhiko K Pennell Nathan N Weir Barbara B Verhaak Roel R Ladd-Acosta Christine C Golub Todd T Gruidl Michael M Sharma Anupama A Szoke Janos J Zakowski Maureen M Rusch Valerie V Kris Mark M Viale Agnes A Motoi Noriko N Travis William W Conley Barbara B Seshan Venkatraman E VE Meyerson Matthew M Kuick Rork R Dobbin Kevin K KK Lively Tracy T Jacobson James W JW Beer David G DG

Nature medicine 20080720 8

Although prognostic gene expression signatures for survival in early-stage lung cancer have been proposed, for clinical application, it is critical to establish their performance across different subject populations and in different laboratories. Here we report a large, training-testing, multi-site, blinded validation study to characterize the performance of several prognostic models based on gene expression for 442 lung adenocarcinomas. The hypotheses proposed examined whether microarray measur ...[more]

PMID: 18641660

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Project description:A key step in bringing gene expression data into clinical practice is the conduct of large studies to confirm preliminary models. The performance of such confirmatory studies and the transition to clinical practice requires that microarray data from different laboratories are comparable and reproducible. We designed a study to assess the comparability of data from four laboratories that will conduct a larger microarray profiling confirmation project in lung adenocarcinomas. To test the feasibility of combining data across laboratories, frozen tumor tissues, cell line pellets, and purified RNA samples were analyzed at each of the four laboratories. Samples of each type and several subsamples from each tumor and each cell line were blinded before being distributed. The laboratories followed a common protocol for all steps of tissue processing, RNA extraction, and microarray analysis using Affymetrix Human Genome U133A arrays. High within-laboratory and between-laboratory correlations were observed on the purified RNA samples, the cell lines, and the frozen tumor tissues. Intraclass correlation within laboratories was only slightly stronger than between laboratories, and the intraclass correlation tended to be weakest for genes expressed at low levels and showing small variation. Finally, hierarchical cluster analysis revealed that the repeated samples clustered together regardless of the laboratory in which the experiments were done. The findings indicate that under properly controlled conditions it is feasible to perform complete tumor microarray analysis, from tissue processing to hybridization and scanning, at multiple independent laboratories for a single study. dobbi-00100 Assay Type: Gene Expression Provider: Affymetrix Array Designs: HG-U133A Organism: Homo sapiens (ncbitax) Tissue Sites: Kidney, Lung, Stomach, Uterus, Liver, Lymphoid tissue, Ovary, Skin, Adrenal Gland, Lymph_Node Material Types: cell, nuclear_RNA, synthetic_RNA, organism_part, total_RNA Disease States: Recurrent Renal Cell Carcinoma, Squamous Cell Carcinoma,Conventional_Clear_Cell_Renal_Cell_Carcinoma,Gastrointestinal_Stromal_Tumor, Lung_Adenocarcinoma, Leiomyoma, Non neoplastic liver with cirrosis, Stomach Adenocarcinoma, Large Cell Lymphoma, Ovarian Adenocarcinoma, Melanoma, Malignant G1 Stromal Tumor, Adrenal Cortical Adenoma, Metastatic Renal Cell Carcinoma, Malignant Melanoma

Project description:To assess pathologic complete response (pCR), clinical response, feasibility, safety, and potential predictors of response to preoperative trastuzumab plus vinorelbine in patients with operable, human epidermal growth factor receptor 2 (HER2)-positive breast cancer. EXPERIMENTAL DESIGN: 48 patients received preoperative trastuzumab and vinorelbine weekly for 12 weeks. Single and multigene biomarker studies were done in an attempt to identify predictors of response. RESULTS: 8 of 40 (20%) patients achieved pCR (95% confidence interval, 9-36%). Of 9 additional patients recruited for protocol-defined toxicity analysis, 8 were evaluable; 42 of 48 (88%) patients had clinical response (16 patients, clinical complete response; 26 patients, clinical partial response). T(1) tumors more frequently exhibited clinical complete response (P = 0.05) and showed a trend to exhibit pCR (P = 0.07). 5 (13%) patients experienced grade 1 cardiac dysfunction during preoperative treatment. Neither HER2 nor estrogen receptor status changed significantly after exposure to trastuzumab and vinorelbine. RNA profiling identified three top-level clusters by unsupervised analysis. Tumors with extremes of response [pCR (n = 3) versus nonresponse (n = 3)] fell into separate groups by hierarchical clustering. No predictive genes were identified in pCR tumors. Nonresponding tumors were more likely to be T(4) stage (P = 0.02) and express basal markers (P < 0.00001), growth factors, and growth factor receptors. Insulin-like growth factor-I receptor membrane expression was associated with a lower response rate (50% vs 97%; P = 0.001). CONCLUSIONS: Preoperative trastuzumab plus vinorelbine is active and well tolerated in patients with HER2-positive, operable, stage II/III breast cancer. HER2-overexpressing tumors with a basal-like phenotype, or with expression of insulin-like growth factor-I receptor and other proteins involved in growth factor pathways, are more likely to be resistant to this regimen. harri-00137 Assay Type: Gene Expression Provider: Affymetrix Array Designs: HG-U133_Plus_2 Organism: Homo sapiens (ncbitax)

Dataset Information

CaArray_jacob-00182: Gene expression-based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study

Publications

Gene expression-based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study.

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