Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Identification of miRNAs specific for prostate cancer (PCa)

ABSTRACT: The purpose of this study are: - To identify new biomarkers specific for prostate cancer (PCa) that can be used as diagnostic markers in the urine of individuals with high probability of PCa (abnormal PSA and/or digital rectal examination). - To validate the utility of these new biomarkers, as well as others already known such as PCA3, fusion gene TMPRSS2-ERG, GOLPH2 and SPINK1. - To establish a prediction model for the diagnosis of PCa based on the expression of these biomarkers. - To validate this model within the framework of an opportunist programme of early diagnosis. - Within the framework of this programme, to associate a series of social-demographic, antropometric, life-style and occupational variables for establishing a risk model predictor that could be associated with the model based on the biomarkers. Methodology: The study is divided in three phases based on three different cohorts of patients: -Phase 1. Identification of biomarkers. This phase includes 60 patients (10 normal prostates and 50 PCa). Form these tumors a screening of miRNAs will be performed. -Phase 2. Validation of the new biomarkers and others already known by means qRT-PCR on urine samples from 300 patients (200 with histological diagnosis of PCa and 100 with an histological negative result). -Phase 3. Prospective validation in a prospective cohort iof 1065 patients included in an opportunist programme of early detection of PCa.

ORGANISM(S): Homo sapiens

SUBMITTER: JOSE LOPEZ-GUERRERO

PROVIDER: E-GEOD-45604 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:A sensitive assay to identify biomarkers that can accurately diagnose the onset of breast cancer using non-invasively collected clinical specimens is ideal for early detection. In this study, we have conducted a prospective sample collection and retrospective blinded validation (PRoBE design) to evaluate the performance and translational utilities of salivary transcriptomic and proteomic biomarkers for the non-invasive detection of breast cancer. The Affymetrix HG U133 Plus 2.0 Array and 2D-DIGE were used to profile transcriptomes and proteomes in saliva supernatants respectively. Significant variations of salivary transcriptomic and proteomic profiles were observed between breast cancer patients and healthy controls. Eleven transcriptomic biomarker candidates and two proteomic biomarker candidates were selected for a preclinical validation using an independent sample set. Transcriptomic biomarkers were validated by RT-qPCR and proteomic biomarkers were validated by quantitative protein immunoblot. Eight mRNA biomarkers and one protein biomarker have been validated for breast cancer detection, yielding ROC-plot AUC values between 0.665 and 0.959. This report provides proof of concept of salivary biomarkers for the non-invasive detection of breast cancer. The salivary biomarkersâ discriminatory power paves the way for a PRoBE-design definitive validation study. Keywords: Salivary biomarker, Breast cancer, Early detection, Salivary transcriptome, Salivary proteome This study, which was approved by the UCLA and Cedars-Sinai Medical Center Institutional Review Boards (#06-07-043 and #3870, respectively), started sample collection in February 2007. The sample collection followed the PRoBE principle (prospective specimen collection). The saliva bank for breast cancer project at the UCLA Dental Research Institute in collaboration with Cedars Sinai Medical Center has collected 200 saliva samples since 2007 with all subjects recruited from the Saul and Joyce Brandman Breast Cancer Center. Of these, 113 samples, including 41 breast cancer patients and 72 healthy control individuals, were selected for the discovery and validation phase of this study. Inclusion criteria of cancer patients consisted of a confirmed diagnosis of breast cancer. Exclusion criteria of cancer patients included therapy/surgery and/or a diagnosis of other malignancies within 5 years prior to saliva collection. Exclusion criteria of control patients included a diagnosis of any malignancies within 5 years prior to saliva collection. Written informed consents and questionnaire data sheets were obtained from all patients who agreed to serve as saliva donors. Unstimulated saliva samples were consistently collected, stabilized, and preserved as previously described. The sample supernatants were reserved at -80 C prior to assay. This study consisted of a discovery phase, followed by an independent preclinical validation phase. Of the 113 samples, 10 breast cancer samples and 10 healthy control samples were chosen for the discovery phase. All breast cancer cases are invasive ductal carcinoma (IDC), the most common type of breast cancer. Biomarkers identified from the discovery studies were first verified using the discovery sample set. An independent sample set, including 31 breast cancer patients and 62 healthy control subjects, was used for the biomarker validation phase.

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Identification of miRNAs specific for prostate cancer (PCa)

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