Dataset Information

Protein Signatures to Distinguish Aggressive from Indolent Prostate Cancer

ABSTRACT: We performed a mass spectrometry-based proteomic analysis of normal and malignant prostate tissues from 22 men who underwent surgery for prostate cancer. Prostate cancer samples included Grade Groups (3 to 5), with 8 patients experiencing recurrence and 14 without evidence of recurrence with a mean of 6.8 years of follow-up.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Prostate Gland

DISEASE(S): Prostate Cancer

SUBMITTER: Sharon Pitteri

LAB HEAD: Sharon Pitteri

PROVIDER: PXD028118 | Pride | 2022-05-04

REPOSITORIES: Pride

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Publications

Protein signatures to distinguish aggressive from indolent prostate cancer.

Garcia-Marques Fernando F Liu Shiqin S Totten Sarah M SM Bermudez Abel A Tanimoto Cheylene C Hsu En-Chi EC Nolley Rosalie R Hembree Amy A Stoyanova Tanya T Brooks James D JD Pitteri Sharon J SJ

The Prostate 20220131 5

<h4>Background</h4>Distinguishing men with aggressive from indolent prostate cancer is critical to decisions in the management of clinically localized prostate cancer. Molecular signatures of aggressive disease could help men overcome this major clinical challenge by reducing unnecessary treatment and allowing more appropriate treatment of aggressive disease.<h4>Methods</h4>We performed a mass spectrometry-based proteomic analysis of normal and malignant prostate tissues from 22 men who underwen ...[more]

PMID: 35098564

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Project description:BACKGROUND: In previous studies using candidate gene approaches, low sperm count (oligospermia) has been associated with altered sperm mRNA content and DNA methylation in both imprinted and non-imprinted genes. We performed a genome-wide analysis of sperm DNA methylation and mRNA content to test for associations with sperm function. METHODS AND RESULTS: Sperm DNA and mRNA were isolated from 21 men with a range of semen parameters presenting to a tertiary male reproductive health clinic. DNA methylation was measured with the Illumina Infinium array at 27,000 CpG loci. Unsupervised clustering of methylation data differentiated the 21 sperm samples by their motility values. Recursively partitioned mixture modeling (RPMM) of methylation data resulted in four distinct methylation profiles that were significantly associated with sperm motility (P=0.01). Linear models of microarray analysis (LIMMA) was performed based on motility and identified 9,189 CpG loci with significantly altered methylation (Q<0.05) in the low motility samples, with many loci located in genes associated with subfertility and epigenetic regulation. In the low motility samples, the majority of disrupted CpG loci (80%) were hypomethylated. Of the aberrantly methylated CpGs, 194 were associated with imprinted genes almost equally distributed into hypermethylated (predominantly paternally expressed) and hypomethylated (predominantly maternally expressed) groups. Sperm mRNA was measured with the Human Gene 1.0 ST Affymetrix GeneChip Array. LIMMA analysis based on motility identified 20 candidate transcripts as differentially expressed in low motility sperm, including HDAC1 (NCBI 3065), SIRT3 (NCBI 23410), and DNMT3A (NCBI 1788). Altered expression of these epigenetic regulatory genes was associated with RPMM DNA methylation class. CONCLUSIONS: Using integrative genome-wide approaches to study epigenetic and gene expression patterns in human sperm we identified CpG methylation profiles and mRNA alterations associated with low sperm motility, and that low motility sperm may have aberrant genome-wide hypomethylation due to excess HDAC1 activity. See summary above

Dataset Information

Protein Signatures to Distinguish Aggressive from Indolent Prostate Cancer

Publications

Protein signatures to distinguish aggressive from indolent prostate cancer.

Similar Datasets

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