Integrated RNA and metabolite profiling of urine liquid biopsies for prostate cancer biomarker discovery

AbstractSensitive and specific diagnostic and prognostic biomarkers for prostate cancer (PCa) are urgently needed. Urine samples are a non-invasive means to obtain abundant and readily accessible “liquid biopsies”. Herein we used urine liquid biopsies to identify and characterize a novel group of urine-enriched RNAs and metabolites in PCa patients and normal individuals with or without benign prostatic disease. Differentially expressed RNAs were identified in urine samples by deep sequencing and metabolites in urine were measured by mass spectrometry. The mRNA and metabolite profiles were distinct in patients with benign and malignant disease. Integrated analysis of urinary gene expression and metabolite signatures unveiled an aberrant glutamate metabolism and tricarboxylic acid (TCA) cycle node in prostate cancer-derived cells. Functional validation supports a role for glutamate metabolism and glutamate oxaloacetate transaminase 1 (GOT1)-dependent redox balance in prostate cancer, which can be exploited for novel biomarkers and therapies.

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Integrated analysis of epigenomic and genomic changes by DNA methylation dependent mechanisms provides potential novel biomarkers for prostate cancer

Oncotarget ◽

10.18632/oncotarget.2313 ◽

2014 ◽

Vol 5 (17) ◽

pp. 7858-7869 ◽

Cited By ~ 9

Author(s):

Nicole M. A. White-Al Habeeb ◽

Linh T. Ho ◽

Ekaterina Olkhov-Mitsel ◽

Ken Kron ◽

Vaijayanti Pethe ◽

...

Keyword(s):

Prostate Cancer ◽

Dna Methylation ◽

Integrated Analysis ◽

Genomic Changes ◽

Novel Biomarkers

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Identification of novel biomarkers of prostate cancer through integrated analysis

Translational Andrology and Urology ◽

10.21037/tau-21-401 ◽

2021 ◽

Vol 0 (0) ◽

pp. 0-0

Author(s):

Pu Zhang ◽

Bei Qian ◽

Zijian Liu ◽

Decai Wang ◽

Fang Lv ◽

...

Keyword(s):

Prostate Cancer ◽

Integrated Analysis ◽

Novel Biomarkers

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Integrated RNA and metabolite profiling of urine liquid biopsies for prostate cancer biomarker discovery

Scientific Reports ◽

10.1038/s41598-020-60616-z ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 4

Author(s):

Bongyong Lee ◽

Iqbal Mahmud ◽

John Marchica ◽

Paweł Dereziński ◽

Feng Qi ◽

...

Keyword(s):

Prostate Cancer ◽

Metabolite Profiling ◽

Biomarker Discovery ◽

Cancer Biomarker ◽

Liquid Biopsies

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Metabolomics Contributions to the Discovery of Prostate Cancer Biomarkers

Metabolites ◽

10.3390/metabo9030048 ◽

2019 ◽

Vol 9 (3) ◽

pp. 48 ◽

Cited By ~ 11

Author(s):

Nuria Gómez-Cebrián ◽

Ayelén Rojas-Benedicto ◽

Arturo Albors-Vaquer ◽

José López-Guerrero ◽

Antonio Pineda-Lucena ◽

...

Keyword(s):

Prostate Cancer ◽

Biomarker Discovery ◽

Tca Cycle ◽

Tricarboxylic Acid ◽

Metabolic Signature ◽

Diagnosis And Prognosis ◽

Clinical Biomarkers ◽

Specificity And Sensitivity ◽

Fatty Acids Metabolism ◽

Patient Prognosis

Prostate cancer (PCa) is one of the most frequently diagnosed cancers and a leading cause of death among men worldwide. Despite extensive efforts in biomarker discovery during the last years, currently used clinical biomarkers are still lacking enough specificity and sensitivity for PCa early detection, patient prognosis, and monitoring. Therefore, more precise biomarkers are required to improve the clinical management of PCa patients. In this context, metabolomics has shown to be a promising and powerful tool to identify novel PCa biomarkers in biofluids. Thus, changes in polyamines, tricarboxylic acid (TCA) cycle, amino acids, and fatty acids metabolism have been reported in different studies analyzing PCa patients’ biofluids. The review provides an up-to-date summary of the main metabolic alterations that have been described in biofluid-based studies of PCa patients, as well as a discussion regarding their potential to improve clinical PCa diagnosis and prognosis. Furthermore, a summary of the most significant findings reported in these studies and the connections and interactions between the different metabolic changes described has also been included, aiming to better describe the specific metabolic signature associated to PCa.

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Advances and Perspectives in Prostate Cancer Biomarker Discovery in the Last 5 Years through Tissue and Urine Metabolomics

Metabolites ◽

10.3390/metabo11030181 ◽

2021 ◽

Vol 11 (3) ◽

pp. 181

Author(s):

Ana Rita Lima ◽

Joana Pinto ◽

Filipa Amaro ◽

Maria de Lourdes Bastos ◽

Márcia Carvalho ◽

...

Keyword(s):

Prostate Cancer ◽

Biomarker Discovery ◽

Specific Antigen ◽

Cancer Biomarker ◽

Metabolic Reprogramming ◽

The Past ◽

Promising Strategy ◽

Ideal Approach ◽

Novel Biomarkers ◽

The Impact

Prostate cancer (PCa) is the second most diagnosed cancer in men worldwide. For its screening, serum prostate specific antigen (PSA) test has been largely performed over the past decade, despite its lack of accuracy and inability to distinguish indolent from aggressive disease. Metabolomics has been widely applied in cancer biomarker discovery due to the well-known metabolic reprogramming characteristic of cancer cells. Most of the metabolomic studies have reported alterations in urine of PCa patients due its noninvasive collection, but the analysis of prostate tissue metabolome is an ideal approach to disclose specific modifications in PCa development. This review aims to summarize and discuss the most recent findings from tissue and urine metabolomic studies applied to PCa biomarker discovery. Eighteen metabolites were found consistently altered in PCa tissue among different studies, including alanine, arginine, uracil, glutamate, fumarate, and citrate. Urine metabolomic studies also showed consistency in the dysregulation of 15 metabolites and, interestingly, alterations in the levels of valine, taurine, leucine and citrate were found in common between urine and tissue studies. These findings unveil that the impact of PCa development in human metabolome may offer a promising strategy to find novel biomarkers for PCa diagnosis.

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Plasma Metabolomics Characteristic of Gout Patients With Regular Glucose, Blood Pressure, and Blood Lipid

10.21203/rs.3.rs-126057/v1 ◽

2020 ◽

Author(s):

Baoyu Zhang ◽

Lijie Zhang ◽

Yuan Wang ◽

Zongwei Wang ◽

Caiyan Mo ◽

...

Keyword(s):

Blood Lipid ◽

Tca Cycle ◽

Negative Ion ◽

Control Group ◽

Methionine Metabolism ◽

Glutamate Metabolism ◽

Citrate Cycle ◽

Orthogonal Signal Correction ◽

Novel Biomarkers ◽

Negative Ion Mode

Abstract BackgroundGout is a metabolic disease and is the most common form of inflammatory arthritis affecting men. However, the pathogenesis of gout is still uncertain, and novel biomarkers are needed for early prediction and diagnosis of gout. The aim of this study is to reveal the metabolic alterations in plasma of gout patients and discover novel molecular biomarkers for early diagnosis. MethodsMetabonomics was employed to screen and identify novel biomarkers of gout based on human plasma. Ultra High-Pressure Liquid Chromatography-Mass Spectrometry (UHPLC-MS) and orthogonal signal correction partial least squares discriminate analysis (OPLS-DA) were also used for metabonomics study. Kyoto Encyclopedia of Genes and Genomes (KEGG) and MetaboAnalyst were used for pathway enrichment analysis.ResultsIn this study, 51 metabolites in positive ion mode and 39 metabolites in negative ion mode were selected as remarkable significant variables between gout and healthy control group. Four unique pathways were found, namely Citrate cycle (TCA cycle), cysteine and methionine metabolism and alanine, aspartate, and glutamate metabolism. A total of 7 metabolites with AUC>0.75 were involved in the above three metabolic pathways, including L-Malic acid，Pyruvate，cis-Aconitate, Cysteine-S-sulfate, L-2-Aminobutyric acid, L-Methionine, Succinic semialdehyde.ConclusionThe present study identified the plasma metabolomics characteristic of gout through UHPLC-MS. The differential metabolites pathways of gout screened out were involved in Citrate cycle (TCA cycle), cysteine and methionine metabolism and alanine, aspartate, and glutamate metabolism. The metabolomics characteristic of gout could provide novel insights into the pathogenesis of gout.

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