9 research outputs found
Genome CNVs from leukocytes predicting short PSADT correlated with lower PSA-free survival.
<p>Kaplan-Meier analysis on patients predicted by LSR based on CNV of patients’ leukocytes as likely recurrent and having PSADT 4 months or less versus likely non-recurrent or recurrent but having PSADT 15 months or more (upper left). Similar survival analyses were also performed on case segregations based on Gleason’s grades (upper middle), Nomogram probability (upper right), the status of 8 fusion transcripts (lower left), or a model by combining LSR, Nomogram and fusion transcript status using LDA (lower middle), or a model by combining LSR, Nomogram, Gleason grade and fusion transcript status using LDA (lower right). Number of samples analyzed and p values are indicated.</p
Large LSRs of genome CNVs from leukocytes correlated with lower PSA-free survival.
<p>Kaplan-Meier analysis on patients predicted by LSR based on CNV of patients’ leukocytes as likely recurrent versus likely non-recurrent (upper left). Similar survival analyses were also performed on case segregations based on Gleason’s grades (upper middle), Nomogram probability (upper right), the status of 8 fusion transcripts (lower left), or a model by combining LSR, Nomogram and fusion transcript status using LDA (lower middle), or a model by combining LSR, Nomogram, Gleason grade and fusion transcript status using LDA (lower right). Number of samples analyzed and p values are indicated.</p
LSR of genome CNV from leukocytes to predict prostate cancer recurrence with short PSADT.
<p>LSR derived from leukocyte genome CNV predicts PSADT 4 months or less. ROC analysis using LSRs derived from leukocyte CNVs as a prediction parameter (red) to predict PSADT 4 months or less, versus Nomogram (blue), Gleason’s grade (green) and the status of 8 fusion transcripts[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135982#pone.0135982.ref014" target="_blank">14</a>] (yellow). Samples were analyzed by the same procedure as <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135982#pone.0135982.g003" target="_blank">Fig 3</a>. (B) Combination of LSR (L), Gleason’s grade (G), Nomogram (N) and the status of fusion transcripts (F) to predict prostate cancer recurrent PSADT 4 months or less. ROC analysis of a model combining LSR, fusion transcripts, Nomogram and Gleason’s grade using LDA is indicated by black. ROC analysis of a model combining fusion transcripts, Nomogram and Gleason’s grade using LDA is indicated by red. ROC analysis of a model combining LSR, fusion transcripts and Gleason’s grade using LDA is indicated by blue. ROC analysis of a model combining LSR, fusion transcripts and Nomogram using LDA is indicated by green. ROC analysis of a model combining LSR, Nomogram and Gleason’s grade is indicated by yellow.</p
Prediction of prostate cancer recurrence based on leukocyte LSR, Gleason, Nomogram and fusion transcript status.
<p>L-LSR; N-Nomogram; F-fusion transcript status; G-Gleason grade.</p><p>L+N+F: LDA model to combine LSR, Nomogram and fusion transcript status</p><p>L+N+G: LDA model to combine LSR, Nomogram and Gleason grade</p><p>N+F+G: LDA model to combine Nomogram, fusion transcript status and Gleason grade</p><p>L+N+F+G: LDA model to combine LSR, Nomogram, fusion transcript status and Gleason grade.</p><p>The results represent the average of the analyses on 10 random equal splits of training and testing results.</p><p>Prediction of prostate cancer recurrence based on leukocyte LSR, Gleason, Nomogram and fusion transcript status.</p
LSR of genome CNV from leukocytes to predict prostate cancer recurrence.
<p>(A) LSR derived from leukocyte genome CNV predicts prostate cancer recurrence. Receiver operating curve (ROC) analyses using LSRs derived from leukocyte CNVs as prediction parameter (red) to predict prostate cancer recurrence, versus Nomogram (blue), Gleason’s grade (green) and the status of 8 fusion transcripts[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135982#pone.0135982.ref014" target="_blank">14</a>] (yellow). The samples were equally split randomly into training and testing sets 10 times. The ROC analysis represents the results from the most representative split. (B) Combination of LSR (L), Gleason’s grade (G), Nomogram (N) and the status of fusion transcripts (F) to predict prostate cancer recurrence. ROC analysis of a model combining LSR, fusion transcripts, Nomogram and Gleason’s grade using LDA is indicated by black. ROC analysis of a model combining fusion transcripts, Nomogram and Gleason’s grade using LDA is indicated by red. ROC analysis of a model combining LSR, fusion transcripts and Gleason’s grade using LDA is indicated by blue. ROC analysis of a model combining LSR, fusion transcripts and Nomogram using LDA is indicated by green. ROC analysis of a model combining LSR, Nomogram and Gleason’s grade is indicated by yellow. Similar random splits of training and testing data sets were performed as of (A).</p
Large size ratio (LSR) of CNVs from leukocytes from prostate cancer patients are correlated with aggressive behavior of prostate cancer.
<p>(A) Schematic diagram of LSR model of leukocyte CNV. (B) LSRs from leukocytes are associated with aggressive prostate cancer recurrence behavior. Upper panel: Correlation of LSRs from leukocyte genomes with prostate cancers that were recurrent; Lower panel: Correlation of LSRs from leukocyte genomes with prostate cancers that were non-recurrent 90 months after radical prostatectomy. (C) LSRs from leukocytes are associated with short PSADT. Upper panel: Correlation of LSRs from leukocyte genomes with prostate cancers that had recurrent serum prostate specific antigen doubling time (PSADT) 4 months or less; Lower panel: Correlation of LSRs from leukocyte genomes with prostate cancers that were not recurrent or recurrent but having PSADT 15 months or more.</p
Copy number variations (CNV) in blood and prostate cancer from prostate cancer patients.
<p>(A) Histogram of frequency of amplification (red) or deletion (blue) of genome sequences of leukocytes (upper panel, n = 273) from prostate cancer patients. (B) Manhattan plots of p-values in association with prostate cancer recurrence of each gene CNV from leukocytes.</p
Relative Quantitation of Proteins in Expressed Prostatic Secretion with a Stable Isotope Labeled Secretome Standard
Expressed prostatic secretion (EPS) is a proximal fluid directly derived from the prostate and, in the case of prostate cancer (PCa), is hypothesized to contain a repertoire of cancer-relevant proteins. Quantitative analysis of the EPS proteome may enable identification of proteins with utility for PCa diagnosis and prognosis. The present investigation demonstrates selective quantitation of proteins in EPS samples from PCa patients using a stable isotope labeled proteome standard (SILAP) generated through the selective harvest of the “secretome” from the PC3 prostate cancer cell line grown in stable isotope labeled cell culture medium. This stable isotope labeled secretome was digested with trypsin and equivalently added to each EPS digest, after which the resultant mixtures were analyzed by liquid chromatography–tandem mass spectrometry for peptide identification and quantification. Relative quantification of endogenous EPS peptides was accomplished by comparison of reconstructed mass chromatograms to those of the chemically identical SILAP peptides. A total of 86 proteins were quantified from 263 peptides in all of the EPS samples, 38 of which were found to be relevant to PCa. This work demonstrates the feasibility of using a SILAP secretome standard to simultaneously quantify many PCa-relevant proteins in EPS samples
Small Molecule Antagonists of the Nuclear Androgen Receptor for the Treatment of Castration-Resistant Prostate Cancer
After
a high-throughput screening campaign identified thioether <b>1</b> as an antagonist of the nuclear androgen receptor, a zone
model was developed for structure–activity relationship (SAR)
purposes and analogues were synthesized and evaluated in a cell-based
luciferase assay. A novel thioether isostere, cyclopropane (1<i>S</i>,2<i>R</i>)-<b>27</b>, showed the desired
increased potency and structural properties (stereospecific SAR response,
absence of a readily oxidized sulfur atom, low molecular weight, reduced
number of flexible bonds and polar surface area, and drug-likeness
score) in the prostate-specific antigen luciferase assay in C4-2-PSA-rl
cells to qualify as a new lead structure for prostate cancer drug
development