Dataset Information

Peripheral blood proteomic signature of newly diagnosed prostate cancer

ABSTRACT: Prostate cancer (PCa) is the most common malignant tumour, with high incidence rates and heterogeneity in men around the world. It is becoming an increasing burden on the health care system due to lack of tests for precise detection of disease, risk assessment and response to treatments. We used SWATH-MS as a discovery proteomics tool to identify markers in the serum of newly diagnosed PCa patients and healthy controls to facilitate the improved diagnosis. Furthermore, identification and expression of proteins was also determined in patients undergone radiotherapy and prostatectomy for monitoring of the clinical response to respective treatment options. Thus, this study provides the basis for a proteomic signature to improve diagnostics of patients with localised prostate cancer.

INSTRUMENT(S): TripleTOF 6600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Serum

DISEASE(S): Prostate Adenocarcinoma

SUBMITTER: AMMARA MUAZZAM

LAB HEAD: Anthony Whetton

PROVIDER: PXD025484 | Pride | 2023-03-11

REPOSITORIES: Pride

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Publications

A Novel Blood Proteomic Signature for Prostate Cancer.

Muazzam Ammara A Spick Matt M Cexus Olivier N F ONF Geary Bethany B Azhar Fowz F Pandha Hardev H Michael Agnieszka A Reed Rachel R Lennon Sarah S Gethings Lee A LA Plumb Robert S RS Whetton Anthony D AD Geifman Nophar N Townsend Paul A PA

Cancers 20230207 4

Prostate cancer is the most common malignant tumour in men. Improved testing for diagnosis, risk prediction, and response to treatment would improve care. Here, we identified a proteomic signature of prostate cancer in peripheral blood using data-independent acquisition mass spectrometry combined with machine learning. A highly predictive signature was derived, which was associated with relevant pathways, including the coagulation, complement, and clotting cascades, as well as plasma lipoprotein ...[more]

PMID: 36831393

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Project description:15-Lipoxygenase 2 (15-LOX2), a human-specific lipid-peroxidizing enzyme, is mainly expressed in luminal compartment of the normal prostate and often decreased or lost in prostate cancer (PCa). Previous studies from our lab implicate 15-LOX2 as a functional tumor suppressor. To better understand the biological role of 15-LOX2 in vivo, we established prostate-specific 15-LOX2 transgenic mice using the ARR2PB promoter. Unexpectedly, 15-LOX2 expression resulted in age-dependent prostatic hyperplasia. Interestingly, transgenic expression of 15-LOX2sv-b, a splice variant that lacks the arachidonic acid metabolizing activity, also induced hyperplasia and enlargement of the prostate. Prostatic hyperplasia induced by both 15-LOX2 and 15-LOX2sv-b was associated with an increase in proliferative (i..e., Ki67+) and luminal cells but 15-LOX2-induced hyperplasia was also accompanied by a prominent increase in basal cells. Microarray analysis revealed distinct gene expression profiles that could help explain the prostate phenotypes. Strikingly, 15-LOX2 (but not 15-LOX2sv-b) transgenic prostate showed up-regulation of several well-known stem/progenitor cell molecules including Sca-1, Trop2, p63 and Psca. Prostatic hyperplasia caused by both 15-LOX2 and 15-LOX2sv-b did not progress to PCa over >5 years of observations. Mechanistically, hyperplastic prostate lobes (especially those of the 15-LOX2 mice) showed a dramatic increase in senescent cells revealed by increased SA-ßgal, HP1, and p27Kip1 staining. Collectively, our results suggest that 15-LOX2 expression in mouse prostate leads to hyperplasia that activates the senescence checkpoint, which may in turn function as a barrier to tumor development. RNA was isolated from combined prostatic lobes of 6 mice (to reduce inter-animal variation) from ~2.5 month old (young; y) 15-LOX2 (line fl26), 15-LOX2sv-b (line svb9), wild type (wt) and ~15 month old (old; o) wt mice and hybridized onto Agilent's whole mouse genome oligoarrays arrays (G4122A) in fl26y(vs)wty, svb9y(vs)wty and wto(vs)wty combinations. The hybridizations were carried out in duplicates using an independent set of samples (biological replicates).

Dataset Information

Peripheral blood proteomic signature of newly diagnosed prostate cancer

Publications

A Novel Blood Proteomic Signature for Prostate Cancer.

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