Determining Prostate Cancer Aggressiveness Utilizing a Novel DNA Methylation Approach
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE73549 | GEO | 2016/11/30
SECONDARY ACCESSION(S): PRJNA297281
REPOSITORIES: GEO
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Project description:Prostate cancer (PCa) is one of the most prevalent cancers among men and the fifth leading cause of cancer-related death in men. Currently, PCa suspicion is based on abnormal digital rectal examination and/or raised PSA serum levels, with prostate needle biopsy being required for a definitive diagnosis. Histopathological classification of tumours based on GS grading, cancer staging and PSA levels are used to predict the indolent or aggressive progression of the tumour as well as the likelihood of disease recurrence. These diagnosis and prognosis tools for PCa have revealed limited usefulness, especially PSA testing, which despite organ-specificity is not cancer-specific, being associated with low specificity. In this vein, new markers have been proposed in order to increase the accuracy of PCa detection, most of them proteins. Despite the significant efforts that have been undertaken for discovering other biomarkers for PCa management, few were translated into clinical practice. The simple and non-invasive nature of urine collection along with its proteome stability and storing many secreted proteins of prostate origin, makes the identification of PCa urinary biomarkers an attractive approach. With this in mind, we aimed to compare the urinary proteome profile of PCa patients with non-cancer patients in order to identify non-invasive candidate biomarkers for PCa prediction. To fulfil this task, we followed a shotgun LC-MS/MS approach using an Orbitrap instrument. A combination of two different software packages, MaxQuant and Proteome Discover was used to increase the robustness of analysis and enhance the search for new biomarkers. Proteins quantification was based on a label-free quantification approach (false discovery rate (FDR) 1%). The present dataset was used to disclosure potential markers in PCa management.
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Project description:Prostate cancer is the third most frequent cancer in men worldwide, with a notable increase in prevalence over the last two decades. The PSA is the only well-established protein biomarker for prostate cancer diagnosis, staging, and sur-veillance. It frequently leads to inaccurate diagnosis and overtreatment since it is an organ-specific biomarker rather than a tumour-specific biomarker. As a result, one of the primary goals of prostate cancer proteome research is to iden-tify novel biomarkers that can be used with or instead of PSA, particularly in non-invasive blood samples. Thousands of peptides or assays were detected in blood samples from patients with low to high-grade prostate cancer and healthy individuals, allowing data processing of sequential window acquisition of all theoretical mass spectra (SWATH-MS). By assisting in the detection of prostate cancer biomarkers in blood samples, this useful resource will improve our un-derstanding of the role of proteomics in prostate cancer diagnosis and risk assessment.
2021-12-20 | PXD028651 | Pride
Project description:Many human cancers present as multi-focal lesions. Understanding the clonal origin of multi-focal cancers is of both etiological and clinical importance. The molecular basis of multi-focal prostate cancer has previously been explored using only a limited number of isolated markers and, although independent origin is widely believed, the clonal origin of multi-focal prostate cancer is still debatable. We attempted to address clonal origin using a genome-wide copy-number analysis of individual cancer and high-grade prostatic intraepithelial neoplasia (HGPIN) lesions. Using Affymetrix array 6.0 copy-number analysis, we compared the genomic changes detected in 54 individual cancer and HGPIN lesions, isolated from 20 clinically localized prostate cancer cases. Identical genomic copy-number changes, shared by all same-case cancer foci, were detected in all 16 informative multi-tumor cases. In addition, both HGPIN lesions in the two multi-HGPIN cases available shared identical genomic changes. Commonly known genomic alterations, including losses at 6q15, 8p21.3-8p21.2, 10q23.2-10q23.31, 13q21.31-13q21.32, 16q22.3, 16q23.2-16q23.3 and 21q22.2-21q22.3 regions and gain of 8q24.3 were the most frequently detected changes in this multi-focal prostate cancer study, occurring in all same-case foci in at least one case. Microarray data were confirmed by fluorescence in situ hybridization in selected foci. Our high-resolution genome-wide copy-number data suggest that many multi-focal cases derive from a single prostate cancer precursor clone and that this precursor may give rise to separate HGPIN foci, which through clonal expansion may progress to multi-focal invasive prostate cancer. These findings, which demonstrate the monoclonal origin of multi-focal prostate cancer, should significantly enhance our understanding of prostate carcinogenesis and potentially improve clinical management of the disease.
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Project description:A major challenge in the clinical management of prostate cancer is the inability to definitively diagnose indolent versus aggressive cases. Contributing to this challenge is a lack of basic science understanding of the molecular basis behind aggressiveness subtypes in prostate cancer. DNA methylation is the epigenetic addition of a methyl group to the DNA base cytosine and has been found to regulate cell proliferation and environmental adaptation. We hypothesized that DNA methylation changes are a mechanism by which an aggressive cancer attains phenotypes that distinguish it from indolent cases via disruption of regulatory networks. This hypothesis was tested by comparing DNA methylation between benign prostate and both low grade (Gleason score 6) and high grade (Gleason score 8 to 10) groups. Methylome-wide next generation sequencing was performed on formalin-fixed paraffin embedded (FFPE) samples from radical prostatectomy cases using MBD-isolated genome sequencing (MiGS). This technique uses a DNA methylation binding protein (MBD) to purify fragments from a genomic library with a high level of CpG DNA methylation. These fragments were then sequenced via next generation sequencing, the reads were aligned to a reference genome, and then the reads were counted within non-overlapping 50bp windows genome wide. Statistical analysis was then performed on these windowed counts to produce differentially methylated regions (DMRs). MBD-isolated Genome Sequencing (MiGS) for groups of benign prostate (from cystoprostatectomy), low grade prostate cancer (from radical prostatectomy with Gleason Score 6), and high grade prostate cancer (from radical prostatectomy with Gleason Scores 8 to 10) in both European Americans and African Americans
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Project description:"Single nucleotide variant detection in multiple foci of three prostate cancer tumors"
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