Stable isotope metabolic labeling suggests differential turnover of the DPYSL protein family

Turck, Christoph W.; Webhofer, Christian; Nussbaumer, Markus; Teplytska, Larysa; Chen, Alon; Maccarrone, Giuseppina; Filiou, Michaela D.

doi:10.1002/prca.201600078

Cited by 9 publications

(7 citation statements)

References 26 publications

(40 reference statements)

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“…The CRMP family consists of CRMP1-5 (30)(31)(32), some studies have shown that CRMP4 expression is low in PCa. The methylation of CRMP4 promoter leads to a downregulation of CRMP4, which further promotes the invasion and metastasis of PCa and affects the prognosis (18,24,33).…”

Section: Discussionmentioning

confidence: 99%

CRMP4 CpG Hypermethylation Predicts Upgrading to Gleason Score ≥ 8 in Prostate Cancer

Qin

Yang

et al. 2022

Front. Oncol.

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BackgroundThis study determined the predictive value of CRMP4 promoter methylation in prostate tissues collected by core needle biopsies for a postoperative upgrade of Gleason Score (GS) to ≥8 in patients with low-risk PCa.MethodA retrospective analysis of the clinical data was conducted from 631 patients diagnosed with low-risk PCa by core needle biopsy at multiple centers and then underwent Radical Prostatectomy (RP) from 2014-2019. Specimens were collected by core needle biopsy to detect CRMP4 promoter methylation. The pathologic factors correlated with the postoperative GS upgrade to ≥8 were analyzed by logistic regression. The cut-off value for CRMP4 promoter methylation in the prostate tissues collected by core needle biopsy was estimated from the ROC curve in patients with a postoperative GS upgrade to ≥8.ResultMultivariate logistic regression showed that prostate volume, number of positive cores, and CRMP4 promoter methylation were predictive factors for a GS upgrade to ≥8 (OR: 0.94, 95% CI: 0.91-0.98, P=0.003; OR: 3.16, 95% CI: 1.81-5.53, P<0.001; and OR: 1.43, 95% CI: 1.32-1.55, P<0.001, respectively). The positive predictive rate was 85.2%, the negative predictive rate was 99.3%, and the overall predictive rate was 97.9%. When the CRMP4 promoter methylation rate was >18.00%, the low-risk PCa patients were more likely to escalate to high-risk patients. The predictive sensitivity and specificity were 86.9% and 98.8%, respectively. The area under the ROC curve (AUC) was 0.929 (95% CI: 0.883-0.976; P<0.001). The biochemical recurrence (BCR)-free survival, progression-free survival (PFS), and cancer-specific survival (CSS) were worse in patients with CRMP4 methylation >18.0% and postoperative GS upgrade to ≥8 than in patients without an upgrade (P ≤ 0.002).ConclusionA CRMP4 promoter methylation rate >18.00% in prostate cancer tissues indicated that patients were more likely to escalate from low-to-high risk after undergoing an RP. We recommend determining CRMP4 promoter methylation before RP for low-risk PCa patients.

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Section: Discussionmentioning

confidence: 99%

CRMP4 CpG Hypermethylation Predicts Upgrading to Gleason Score ≥ 8 in Prostate Cancer

Qin

Yang

et al. 2022

Front. Oncol.

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“…Among the differentially expressed proteins identified by MALDI-TOF/TOF MS in the present study, several of these have a potential role in nerve growth and differentiation. DPYSL2 belongs to the DPYSL family of proteins (29), which includes five members; these proteins serve important roles in the maturation of the nervous system in humans and in rats (30). DPYSL2, also reported as collapsin response mediator protein 2, and isocitrate dehydrogenase (NADP) have been proposed to be plasma membrane-associated proteins involved in neuronal differentiation, axon growth and guidance, neuronal growth cone collapse and cell migration (31).…”

Section: Discussionmentioning

confidence: 99%

Proteomics analysis of fetal growth restriction and taurine‑treated fetal growth restriction rat brain tissue by 2D�DIGE and MALDI‑TOF/TOF MS analysis

et al. 2019

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Fetal growth restriction (FGR) is caused by placental insufficiency and can lead to short and long-term neurodevelopmental delays. Taurine, one of the most abundant amino acids in the brain, is critical for the normal growth and development of the nervous system; however, the mechanistic role of taurine in neural growth and development remains unknown. The present study investigated the role of taurine in FGR. Specifically, we explored the proteomic profiles of fetal rats at 6 h postpartum by two-dimensional difference gel electrophoresis combined with matrix assisted laser desorption ionization-time-of-flight (TOF)/TOF tandem mass spectrometry; the findings were verified via reverse transcription-quantitative polymerase chain reaction. A total of 31 differentially expressed protein spots were selected. Among these, 31 were matched, including dihydropyrimidinase-related protein 2 and, CRK and peroxiredoxin 2. Functional analysis using the Gene Ontology database and Ingenuity Pathway Analysis demonstrated that the differentially expressed proteins were mainly associated with neuronal differentiation, 'metabolic process', 'biological regulation' and developmental processes. The present study identified several proteins that were differentially expressed in rats with FGR in the presence or absence of taurine administration. The results of the present study suggest a potential role for taurine in the treatment and prevention of FGR.

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“…Although not specifically used for detection of newly synthesized proteins but able to label whole animals, in vivo metabolic labeling using heavy isotope 15 N was described in several studies. For example, for quantification of Drosophila (fruit fly) proteomes [45], for preparation of 15 N-labeled protein standards from mice to compare unlabeled proteomes [46], for identification of variation in expression and turnover of dihydropyrimidinase-related proteins DPYSL3 and DPYSL5 during brain development by incorporation of 15 N into mice diet [47], and for determination of protein turnover rates on whole proteome scale by restricting all the nitrogen in the rodent diet to 15 N (spirulina algae) with reversion to normal 14 N diet with time points at days to years [48]. In addition, there have been various reviews published discussing both the strengths and the weaknesses of chemical and metabolic labeling of model organisms [49], the merits and difficulties of labeling methods for assessing protein turnover and dynamics [50–51], and a review article of stable isotopes and mass spectrometry in life sciences covering a time period from 1920 to 2016 [52].…”

Section: Strategy and Methods To Identify Newly Synthetized Proteins mentioning

confidence: 99%

Exploring ribosome composition and newly synthesized proteins through proteomics and potential biomedical applications

Št́astná

Gottlieb

Eyk

2017

Expert Review of Proteomics

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Introduction: Protein synthesis is the outcome of tightly regulated gene expression which is responsive to a variety of conditions. Efforts are ongoing to monitor individual stages of protein synthesis to ensure maximum efficiency and accuracy. Due to post-transcriptional regulation mechanisms, the correlation between translatome and proteome is higher than between transcriptome and proteome. However, the most accurate approach to assess the key modulators and final protein expression is directly by using proteomics. Areas covered: This review covers various proteomic strategies that were used to better understand post-transcriptional regulation, specifically during and early after translation. The methods that identify both regulatory proteins associated with translational components and newly synthesized proteins are discussed. Expert commentary: Emerging proteomic approaches make it possible to monitor protein dynamics in cells, tissues and whole animals. The ability to detect alteration in protein abundance soon after their synthesis enables earlier recognition of disease causing factors and candidates to prevent/rectify disease phenotype.

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Stable isotope metabolic labeling suggests differential turnover of the DPYSL protein family

Cited by 9 publications

References 26 publications

CRMP4 CpG Hypermethylation Predicts Upgrading to Gleason Score ≥ 8 in Prostate Cancer

CRMP4 CpG Hypermethylation Predicts Upgrading to Gleason Score ≥ 8 in Prostate Cancer

Proteomics analysis of fetal growth restriction and taurine‑treated fetal growth restriction rat brain tissue by 2D�DIGE and MALDI‑TOF/TOF MS analysis

Exploring ribosome composition and newly synthesized proteins through proteomics and potential biomedical applications

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