Dataset Information

Proteomics of prostate cancer serum and plasma using low and high throughput approaches

ABSTRACT: Mass spectrometry-based proteomics has been successfully used to characterize biofluids, most notably blood, for biomarker discovery or to evaluate patients’ underlying diseases. Despite immense progress, challenges such as blood’s large dynamic range or low throughput remain for those types of studies. In this work, we used cutting-edge proteomics technologies to construct labelled and label-free l workflows, capable of quantifying approximately 2,000 proteins in biofluids. With just 70µL of blood and a single depletion strategy, we conducted an analysis of a cohort comprising 64 individuals, comparing prostate cancer patients to healthy donors. The results revealed dozens of differentially expressed proteins in both plasma and serum. Notably, we identified the upregulation of Prostate Specific Antigen (PSA), a well-known biomarker for prostate cancer, in the cancer cohort, along with the discovery of potential novel markers. Most of the differentially regulated proteins were consistently quantified using both the lower-throughput and higher-throughput workflows. Our bioinformatics analysis of the prostate cancer cohort data suggests that some of the newly discovered proteins may be secreted differentially into the bloodstream, making them potential candidates for disease markers.

INSTRUMENT(S): Orbitrap Fusion Lumos, ultraflex

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood

SUBMITTER: Andrew Jarnuczak

LAB HEAD: Andrew Jarnuczak

PROVIDER: PXD046924 | Pride | 2024-05-21

REPOSITORIES: Pride

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Publications

Proteomics of prostate cancer serum and plasma using low and high throughput approaches.

Hamza Ghaith M GM Raghunathan Rekha R Ashenden Stephanie S Zhang Bairu B Miele Eric E Jarnuczak Andrew F AF

Clinical proteomics 20240312 1

Despite progress, MS-based proteomics in biofluids, especially blood, faces challenges such as dynamic range and throughput limitations in biomarker and disease studies. In this work, we used cutting-edge proteomics technologies to construct label-based and label-free workflows, capable of quantifying approximately 2,000 proteins in biofluids. With 70µL of blood and a single depletion strategy, we conducted an analysis of a homogenous cohort (n = 32), comparing medium-grade prostate cancer patie ...[more]

PMID: 38475692

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Project description:Common epithelial cancers are believed to become more aggressive through the accumulation of multiple independent molecular events that lead to the deregulation of cell signaling. However, the discovery that the majority of prostate cancers harbor gene fusions of the 5'-untranslated region of androgen regulated TMPRSS2 promoter with ETS transcription factor family members has brought this paradigm into question1,2. TMPRSS2-ERG gene fusion is the most common molecular sub-type of prostate cancer. Recent work suggests that the TMPRSS2-ERG fusion is associated with a more aggressive clinical phenotype3. In the most advanced castration resistant prostate cancers where the androgen receptor has been inactivated, the TMPRSS2-ERG fusion remains functionally active. Here we show compelling clinical and gene expression data supporting the existence of a TMPRSS2-ERG fusion prostate cancer subclass. Using expression array profiling on 455 primary prostate tumors, we identified an 87 gene expression signature, distinguishing TMPRSS2-ERG fusion prostate cancer as a discrete molecular entity. Computational analysis suggested that this fusion signature was associated with estrogen receptor signaling. Functional studies demonstrated regulation of the TMPRSS2-ERG fusion transcript by estrogenic compounds. These data identify a previously unrecognized mechanism for regulation of the TMPRSS2-ERG, even in the absence of a functional androgen receptor, and thus may have broader implications in the treatment of prostate cancer. Keywords: Prostate cancer, Expression array, Illumina, gene fusion, TMPRSS2, ERG, Signatures, Estrogen Test Cohort: 388 cases from the population based Swedish-Watchful Waiting cohort. The cohort consists of men with localized prostate cancer (clinical stage T1-T2, Mx, N0); Validation cohort: The PhysiciansM-bM-^@M-^Y Health Study (PHS) cohort included 116 US men diagnosed with incidental prostate cancer between 1983 and 2003; 455 cases were annotated for TMPRSS2-ERG fusion. Test Set: GSM208029 ... GSM208392 Validation Set: GSM208404 ... GSM208512

Dataset Information

Proteomics of prostate cancer serum and plasma using low and high throughput approaches

Publications

Proteomics of prostate cancer serum and plasma using low and high throughput approaches.

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