Unknown,Transcriptomics,Genomics,Proteomics

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Expression data from 22 prostate cancer samples - 6 recurrent and 16 recurrence-free from the validation dataset

ABSTRACT: We analyzed the protein-coding and non-coding gene expression profiles of 64 samples of prostate cancer primary tumors. All samples were collected between 1998 and 2001 with informed consent from patients subjected to radical prostatectomy at Hospital Sirio-Libanes in São Paulo. Selected patients were identified with clinical Stage T1-2 prostate cancer and no lymph node involvement, and received no adjuvant treatment after surgery as long as they remained recurrence-free. Biochemical recurrence was defined as an increase in patient blood PSA level to 0.2 ng per mL of blood at any time during the 5-year follow-up after prostatectomy. For this kind of experiment, also called self-self hybridization, the microarrays were cohybridized with each of Cy3- and Cy5-labeled cRNA replicates. This strategy has been used to derive intensity-dependent cutoffs to classify a gene as differentially expressed or divergent in comparative genomic hybridization (CGH) studies. The comparative analysis of constant fold change cutoffs and intensity-dependent ones has been extensively discussed, showing a superior performance of the intensity-dependent strategy. For the validation dataset processing, reference values obtained with the training dataset processin were applied to normalize the validation dataset. These values were: Average ranked intensities (quantile normalization), batch information (batch adjustment), and gene average and standard deviations (z-score transformation. Here we describe the validation of the gene expression profile comprised of 32 protein-coding mRNAs and 6 intronic non-coding RNAs (ncRNAs) in an independent set of 22 samples, 16 from recurrence-free patients and 6 recurrent patients. In order to compare the expression levels of training and independent validation samples, gene intensity levels of samples in the validation dataset were transformed using normalization factors that had been generated with the training dataset.

ORGANISM(S): Homo sapiens

SUBMITTER: Yuri Moreira

PROVIDER: E-GEOD-18917 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Purpose: Building a universal genomic signature predicting the intensity of FDG uptake in diverse metastatic tumors may allow us to understand better the biological processes underlying this phenomenon and their requirements of glucose uptake. Methods: A balanced training set (n=71) of metastatic tumors including some of the most frequent histologies, with matched PET/CT quantification measurements and whole human genome gene expression microarrays, was used to build the signature. Selection of microarray features was carried out exclusively on the basis of their strong association with FDG uptake (as measured by SUVmean35) by means of univariate linear regression. A thorough bioinformatics study of these genes was performed and multivariable models were built by fitting several state of the art regression techniques to the training set for comparison. Results: The 909 probes with the strongest association with the SUVmean35 (comprising 742 identifiable genes and 62 probes not matched to a symbol) were used to build the signature. Partial Least Squares using 3 components (PLS-3) was the best performing model in the training dataset cross-validation (Root Mean Square Error, RMSE=0.443) and was validated further in an independent validation dataset (n=13) obtaining a performance within the 95% CI of that obtained in the training dataset (RMSE=0.645). Significantly overrepresented biological processes correlating with the SUVmean35 were identified beyond glycolysis, such as ribosome biogenesis and DNA replication (correlating with a higher SUVmean35), and cytoskeleton reorganization and autophagy (correlating with a lower SUVmean35), among others. Conclusions: PLS-3 is a signature predicting accurately the intensity of FDG uptake in diverse metastatic tumors. FDG-PET might help in the design of specific targeted therapies directed to counteract the identified malignant biological processes more likely activated in a tumor as inferred from the SUVmean35 and also from its variations in response to antineoplastic treatments.

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Expression data from 22 prostate cancer samples - 6 recurrent and 16 recurrence-free from the validation dataset

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