Non-invasive urinary metabolomic profiling discriminates prostate cancer from benign prostatic hyperplasia

Pérez-Rambla, Clara; Puchades‐Carrasco, Leonor; García-Flores, María; Rubio‐Briones, J.; Löpez‐Guerrero, José Antonio; Pineda‐Lucena, Antonio

doi:10.1007/s11306-017-1194-y

Cited by 62 publications

(42 citation statements)

References 72 publications

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“…The serum pyrimidines pseudouridine, 5,6‐dihydrouridine, 2’‐O‐methyluridine and 5‐methyluridine were elevated in cases compared to their matched control subjects, and the overall pathway showed a strong association. Pseudouridine is a modified nucleoside generated from the degradation of transfer RNA (tRNA), and previous studies have demonstrated elevated levels of modified nucleosides, particularly pseudouridine, in the biological fluids of cancer patients when compared to cancer‐free controls . Dihydrouridine is one of the most common modifications of tRNA and has been related to cancer, cancer cell growth and survival .…”

Section: Discussionmentioning

confidence: 99%

“…Pseudouridine is a modified nucleoside generated from the degradation of transfer RNA (tRNA), and previous studies have demonstrated elevated levels of modified nucleosides, particularly pseudouridine, in the biological fluids of cancer patients when compared to cancer-free controls. 27,28 Dihydrouridine is one of the most common modifications of tRNA and has been related to cancer, 29,30 cancer cell growth and survival. 30 Our data also showed that serum dihydroorotate was inversely associated with lethal prostate cancer risk.…”

Section: Discussionmentioning

confidence: 99%

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Prospective serum metabolomic profiling of lethal prostate cancer

Huang

Mondul

Weinstein

et al. 2019

Intl Journal of Cancer

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Impaired metabolism may play an important role in the pathogenesis of lethal prostate cancer, yet there is a paucity of evidence regarding the association. We conducted a large prospective serum metabolomic analysis of lethal prostate cancer in 523 cases and 523 matched controls nested within the Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention (ATBC) Study. Median time from baseline fasting serum collection to prostate cancer death was 18 years (maximum 30 years). We identified 860 known biochemicals through an ultrahigh‐performance LC–MS/MS platform. Conditional logistic regression models estimated odds ratios (OR) and 95% confidence intervals of risk associated with 1‐standard deviation (s.d.) increases in log‐metabolite signals. We identified 34 metabolites associated with lethal prostate cancer with a false discovery rate (FDR) < 0.15. Notably, higher serum thioproline, and thioproline combined with two other cysteine‐related amino acids and redox metabolites, cystine and cysteine, were associated with reduced risk (1‐s.d. OR = 0.75 and 0.71, respectively; p ≤ 8.2 × 10−5). By contrast, the dipeptide leucylglycine (OR = 1.36, p = 8.2 × 10−5), and three gamma‐glutamyl amino acids (OR = 1.28–1.30, p ≤ 4.6 × 10−4) were associated with increased risk of lethal prostate cancer. Cases with metastatic disease at diagnosis (n = 179) showed elevated risk for several lipids, including especially the ketone body 3‐hydroxybutyrate (BHBA), acyl carnitines, and dicarboxylic fatty acids (1.37 ≤ OR ≤ 1.49, FDR < 0.15). These findings provide a prospective metabolomic profile of lethal prostate cancer characterized by altered biochemicals in the redox, dipeptide, pyrimidine, and gamma‐glutamyl amino acid pathways, whereas ketone bodies and fatty acids were associated specifically with metastatic disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Prospective serum metabolomic profiling of lethal prostate cancer

Huang

Mondul

Weinstein

et al. 2019

Intl Journal of Cancer

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“…As a result, hnRNPM is expected to become a biomarker for predicting the invasiveness of PCa to guide the selection of treatment schemes. At present, most of the studies on PCa biomarkers focus on the specific proteins that are differentially expressed in PCa tissue compared to normal prostate tissue or in different grade groups using the Gleason grading system . We not only studied the expression level of hnRNPM in ADENO and BPH tissues, but also compared its expression in NEPC and ADENO tissues.…”

Section: Discussionmentioning

confidence: 99%

“…To our surprise, no significant changes were detected in specific proteins that are differentially expressed in PCa tissue compared to normal prostate tissue or in different grade groups using the Gleason grading system. 65,68 We not only studied the expression level of hnRNPM in ADENO and BPH tissues, but also compared its expression in NEPC and ADENO tissues. The results suggested that hnRNPM may play a significant role in the occurrence and progression of PCa.…”

Section: Discussionmentioning

confidence: 99%

HnRNPM is a potential mediator of YY1 which promotes EMT in prostate cancer cells

Yang

Zhang

et al. 2019

The Prostate

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Background With the popularity of serum prostate‐specific antigen (PSA) screening, the number of newly diagnosed prostate cancer (PCa) patients is increasing. However, indolent and invasive PCa cannot be distinguished by the PSA level. Here, we mainly explored the role of heterogeneous nuclear ribonucleoprotein M (hnRNPM) in the invasiveness of PCa. Methods Reverse‐transcription quantitative polymerase chain reaction and Western blotting were used to detect the expression of hnRNPM in PCa and benign prostate hyperplasia (BPH) tissue samples as well as PCa cell lines. Immunohistochemistry was applied to detect hnRNPM or Yin Yang 1 (YY1) expression in BPH, prostate adenocarcinoma (ADENO) and neuroendocrine prostate cancer (NEPC) tissue samples. After aberrant hnRNPM expression was detected in C4‐2 and PC3 cells, changes in cell migration and invasion were observed through wound healing and transwell assays, respectively. We also predicted the transcription factor (TF) of hnRNPM through databases and then verified the association between hnRNPM and YY1 using chromatin immunoprecipitation and luciferase assays. Results The hnRNPM expression pattern exhibited a gradual reduction from BPH tissue to ADENO tissue to NEPC tissue, and hnRNPM had lower expression in more aggressive PCa cell lines. The overexpression of hnRNPM could significantly reduce the expression of Twist1, which inhibits the migration and invasion of PCa cells in vitro. In PCa cells, the overexpression of YY1 could promote epithelial‐mesenchymal transition (EMT) by reducing hnRNPM expression. Furthermore, this effect caused by the overexpression of YY1 could be partially attenuated by the simultaneous overexpression of hnRNPM. Conclusions Our study demonstrates that hnRNPM negatively regulates PCa cell migration and invasion, and that hnRNPM expression can be transcriptionally inhibited by YY1. We speculate that hnRNPM may be a biomarker that can assist in assessing PCa aggressiveness.

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“…In this cohort, citrate was not a predictor for PCa, and the significant metabolites choline and leucine did not improve diagnosis compared with PSA measurements. However, Perez‐Rambla et al have recently demonstrated significant metabolic differences in urine samples from PCa patients and BPH, without prior prostate massage . The predictive value of this classification model was moderate and only significant after variable selection, and thus requires validation in independent cohorts.…”

Section: Cancer Detection and Diagnosismentioning

confidence: 97%

NMR‐based metabolomics of biofluids in cancer

et al. 2018

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This review describes the current status of NMR-based metabolomics of biofluids with respect to cancer risk assessment, detection, disease characterization, prognosis, and treatment monitoring. While the metabolism of cancer cells is altered compared with that of non-proliferating cells, the metabolome of blood and urine reflects the entire organism. We conclude that many studies show impressive associations between biofluid metabolomics and cancer progression, but translation to clinical practice is currently hindered by lack of validation, difficulties in biological interpretation, and non-standardized analytical procedures.

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Non-invasive urinary metabolomic profiling discriminates prostate cancer from benign prostatic hyperplasia

Cited by 62 publications

References 72 publications

Prospective serum metabolomic profiling of lethal prostate cancer

Prospective serum metabolomic profiling of lethal prostate cancer

HnRNPM is a potential mediator of YY1 which promotes EMT in prostate cancer cells

NMR‐based metabolomics of biofluids in cancer

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