Urinary biomarkers in prostate cancer: to the miRnome and beyond.
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ABSTRACT:
SUBMITTER: Hoey C
PROVIDER: S-EPMC7214960 | biostudies-literature | 2020 Apr
REPOSITORIES: biostudies-literature
Publications
Urinary biomarkers in prostate cancer: to the miRnome and beyond.
Hoey Christianne C Jeyapala Renu R Boutros Paul C PC Bapat Bharati B Liu Stanley K SK
Translational andrology and urology 20200401 2
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Project description:Exosomes have recently appeared as a novel source of non-invasive cancer biomarkers since tumour-specific molecules can be found in exosomes isolated from biological fluids. We have here investigated the proteome of urinary exosomes by using mass spectrometry to identify proteins differentially expressed in prostate cancer patients compared to healthy male controls. In total, 15 control and 16 prostate cancer samples of urinary exosomes were analyzed. Importantly, 246 proteins were differentially expressed in the two groups. The majority of these proteins (221) were up-regulated in exosomes from prostate cancer patients. These proteins were analyzed according to specific criteria to create a focus list that contained 37 proteins. At 100% specificity, 17 of these proteins displayed individual sensitivities above 60%. Even though several of these proteins showed high sensitivity and specificity for prostate cancer as individual biomarkers, combining them in a multi-panel test has the potential for full differentiation of prostate cancer from non-disease controls. The highest sensitivity, 94%, was observed for transmembrane protein 256 (TM256; chromosome 17 open reading frame 61). LAMTOR proteins were also distinctly enriched with very high specificity for patient samples. TM256 and LAMTOR1 could be used to augment the sensitivity to 100%. Other prominent proteins were V-type proton ATPase 16 kDa proteolipid subunit (VATL), adipogenesis regulatory factor (ADIRF), and several Rab-class members and proteasomal proteins. In conclusion, this study clearly shows the potential of using urinary exosomes in the diagnosis and clinical management of prostate cancer.
| S-EPMC4745805 | biostudies-literature
Project description:The lack of accuracy in the current prostate specific antigen (PSA) test for prostate cancer (PCa) screening causes around 60-75% of unnecessary prostate biopsies. Therefore, alternative diagnostic methods that have better accuracy and can prevent over-diagnosis of PCa are needed. Researchers have examined various potential biomarkers for PCa, and of those fatty acids (FAs) markers have received special attention due to their role in cancer metabolomics. It has been noted that PCa metabolism prefers FAs over glucose substrates for continued rapid proliferation. Hence, we proposed using a urinary FAs based model as a non-invasive alternative for PCa detection. Urine samples collected from 334 biopsy-designated PCa positive and 232 biopsy-designated PCa negative subjects were analyzed for FAs and lipid related compounds by stir bar sorptive extraction coupled with gas chromatography/mass spectrometry (SBSE-GC/MS). The dataset was split into the training (70%) and testing (30%) sets to develop and validate logit models and repeated for 100 runs of random data partitioning. Over the 100 runs, we confirmed the stability of the models and obtained optimal tuning parameters for developing the final FA based model. A PSA model using the values of the patients' PSA test results was constructed with the same cohort for the purpose of comparing the performances of the FA model against PSA test. The FA final model selected 20 FAs and rendered an AUC of 0.71 (95% CI = 0.67-0.75, sensitivity = 0.48, and specificity = 0.83). In comparison, the PSA model performed with an AUC of 0.51 (95% CI = 0.46-0.66, sensitivity = 0.44, and specificity = 0.71). The study supports the potential use of urinary FAs as a stable and non-invasive alternative test for PCa diagnosis.
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Project description:Prostate cancer (PCa) is one of the most prevalent types of cancer in men worldwide; however, the main diagnostic tests available for PCa have limitations and a biopsy is required for histopathological confirmation of the disease. Prostate-specific antigen (PSA) is the main biomarker used for the early detection of PCa, but an elevated serum concentration is not cancer-specific. Therefore, there is a need for the discovery of new non-invasive biomarkers that can accurately diagnose PCa. The present study used trichloroacetic acid-induced protein precipitation and liquid chromatography-mass spectrometry to profile endogenous peptides in urine samples from patients with PCa (n=33), benign prostatic hyperplasia (n=25) and healthy individuals (n=28). Receiver operating characteristic curve analysis was performed to evaluate the diagnostic performance of urinary peptides. In addition, Proteasix tool was used for in silico prediction of protease cleavage sites. Five urinary peptides derived from uromodulin were revealed to be significantly altered between the study groups, all of which were less abundant in the PCa group. This peptide panel showed a high potential to discriminate between the study groups, resulting in area under the curve (AUC) values between 0.788 and 0.951. In addition, urinary peptides outperformed PSA in discriminating between malignant and benign prostate conditions (AUC=0.847), showing high sensitivity (81.82%) and specificity (88%). From in silico analyses, the proteases HTRA2, KLK3, KLK4, KLK14 and MMP25 were identified as potentially involved in the degradation of uromodulin peptides in the urine of patients with PCa. In conclusion, the present study allowed the identification of urinary peptides with potential for use as non-invasive biomarkers in PCa diagnosis.
| S-EPMC10031726 | biostudies-literature
Project description:Prostate cancer (PC) is the second most common cancer in men worldwide. The application of the prostate-specific antigen (PSA) test has improved the diagnosis and treatment of PC. However, the PSA test has become associated with overdiagnosis and overtreatment. Therefore, there is an unmet need for novel diagnostic, prognostic, and predictive biomarkers of PC. Urinary glycoproteins and exosomes are a potential source of PC glycan biomarkers. Urinary glycan profiling can provide noninvasive monitoring of tumor heterogeneity and aggressiveness throughout a treatment course. However, urinary glycan profiling is not popular due to technical disadvantages, such as complicated structural analysis that requires specialized expertise. The technological development of glycan analysis is a rapidly advancing field. A lectin-based microarray can detect aberrant glycoproteins in urine, including PSA glycoforms and exosomes. Glycan enrichment beads can enrich the concentration of N-linked glycans specifically. Capillary electrophoresis, liquid chromatography-tandem mass spectrometry, and matrix-assisted laser desorption/ionization-time of flight mass spectrometry can detect glycans directory. Many studies suggest potential of urinary glycoproteins, exosomes, and glycosyltransferases as a biomarker of PC. Although further technological challenges remain, urinary glycan analysis is one of the promising approaches for cancer biomarker discovery.
| S-EPMC8100853 | biostudies-literature
Project description:Prostate cancer (PCa) is one of the most prevalent cancer types in men worldwide. However, the main diagnostic tests available for PCa have limitations and need biopsy for histopathological confirmation of the disease. The prostate-specific antigen (PSA) is the main biomarker used for PCa early detection, but an elevated serum concentration is not cancer-specific. Therefore, there is a need for discovery of new non-invasive biomarkers that can accurately diagnose PCa. Here, we used trichloroacetic acid-induced protein precipitation and liquid chromatography-mass spectrometry to profile endogenous peptides in urine samples from patients with PCa (n = 33), benign prostatic hyperplasia (n = 25), and healthy individuals (n = 28). Receiver operating characteristic (ROC) curves were performed to evaluate the diagnostic performance of urinary peptides. In addition, proteasix tool was used for in silico prediction of protease cleavage sites. We found five urinary peptides derived from uromodulin significantly altered between the study groups, all of which were less abundant in the PCa group. In addition, urinary peptides outperformed PSA in discriminating between malignant and benign prostate conditions (AUC = 0.847), showing high sensitivity (81.82%) and specificity (88%). Overall, our study allowed the identification of urinary peptides with potential for use as non-invasive biomarkers in PCa diagnosis.
2022-10-25 | PXD037031 | Pride
Project description:Prostate cancer (PCa) is the second most common cancer of men and is typically slow-growing and asymptomatic. The use of blood PSA as a screening method has greatly improved PCa diagnosis, but high levels of false positives has raised much interest in alternative biomarkers. We used next-generation sequencing (NGS) to elucidate the urinary transcriptome of whole urine collected from high-stage and low-stage PCa patients as well as from patients with the confounding diagnosis of benign hyperplasia (BPH). We identified and validated five differentially expressed protein-coding genes (FTH1 BRPF1, OSBP, PHC3, and UACA) in an independent validation cohort of small-volume (1 mL) centrifuged urine (n = 94) and non-centrifuged urine (n = 84) by droplet digital (dd)PCR. These biomarkers were able to discriminate between BPH and PCa patients and healthy controls using either centrifuged or non-centrifuged whole urine samples, suggesting that the urinary transcriptome is a valuable source of non-invasive biomarkers for PCa that warrants further investigation.
| S-EPMC7072374 | biostudies-literature
Project description:Prostate cancer is the second most common male cancer worldwide showing the highest rates of incidence in Western Europe. Although the measurement of serum prostate-specific antigen levels is the current gold standard in PCa diagnosis, PSA-based screening is not considered a reliable diagnosis and prognosis tool due to its lower sensitivity and poor predictive score which lead to a 22%-43% overdiagnosis, unnecessary biopsies, and over-treatment. These major limitations along with the heterogeneous nature of the disease have made PCa a very unappreciative subject for diagnostics, resulting in poor patient management; thus, it urges to identify and validate new reliable PCa biomarkers that can provide accurate information in regard to disease diagnosis and prognosis. Researchers have explored the analysis of microRNAs (miRNAs), messenger RNAs (mRNAs), small proteins, genomic rearrangements, and gene expression in body fluids and non-solid tissues in search of lesser invasive yet efficient PCa biomarkers. Although the presence of miRNAs in body fluids like blood, urine, and saliva initially sparked great interest among the scientific community; their potential use as liquid biopsy biomarkers in PCa is still at a very nascent stage with respect to other well-established diagnostics and prognosis tools. Up to date, numerous studies have been conducted in search of PCa miRNA-based biomarkers in whole blood or blood serum; however, only a few studies have investigated their presence in urine samples of which less than two tens involve the detection of miRNAs in extracellular vesicles isolated from urine. In addition, there exists some discrepancy around the identification of miRNAs in PCa urine samples due to the diversity of the urine fractions that can be targeted for analysis such as urine circulating cells, cell-free fractions, and exosomes. In this review, we aim to discuss research output from the most recent studies involving the analysis of urinary EVs for the identification of miRNA-based PCa-specific biomarkers.
| S-EPMC9895092 | biostudies-literature
Project description:BackgroundSignificant numbers of prostate cancer (PCa) patients experience tumour upstaging and upgrading in surgical specimens that cause serious problems in timely and proper selection of the treatment strategy. This study was aimed at the evaluation of a set of established epigenetic biomarkers as a noninvasive tool for more accurate PCa categorization before radical prostatectomy (RP).MethodsQuantitative methylation-specific PCR was applied for the methylation analysis of RARB, RASSF1, and GSTP1 in 514 preoperatively collected voided or catheterized urine samples from the single-centre cohort of 1056 treatment-naïve PCa patients who underwent RP. The rates of biopsy upgrading and upstaging were analysed in the whole cohort.ResultsPathological examination of RP specimens revealed Gleason score upgrading in 27.2% and upstaging in 20.3% of the patients with a total misclassification rate of 39.0%. DNA methylation changes in at least one gene were detected in more than 80% of urine samples. Combination of the PSA test with the three-gene methylation analysis in urine was a significant predictor of pathological upstaging and upgrading (P < 0.050), however, with limited increase in overall accuracy. The PSA test or each gene alone was not informative enough.ConclusionsThe urinary DNA methylation assay in combination with serum PSA may predict tumour stage or grade migration post-RP aiding in improved individual risk assessment and appropriate treatment selection. Clinical utility of these biomarkers should be proven in larger multi-centre studies.
| S-EPMC6683454 | biostudies-literature
Project description:Current screening methods towards prostate cancer (PCa) are not without limitations. Research work has been on-going to assess if there are other better tests suitable for primary or secondary screening of PCa to supplement the serum prostate specific antigen (PSA) test, which fails to work accurately in a grey zone of 4-10ng/ml. In this pilot study, the potential roles of urinary polyamines as prostate cancer biomarkers were evaluated. PCa, benign prostatic hyperplasia (BPH) patients and healthy controls (HC) showing PSA>4.0ng/ml were enrolled in the study. Their urine samples were obtained, and the urinary levels of putrescine (Put), spermidine (Spd) and spermine (Spm) were determined by ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometer (UPLC-MS/MS). Receiver operating characteristics (ROC) curve and Student's t-test were used to evaluate their diagnostic accuracies. Among the three biogenic polyamines, Spm had demonstrated a good diagnostic performance when comparing their levels in PCa patients with BPH patients (1.47 in PCa vs 5.87 in BPH; p<0.0001). Results are in accordance with transrectal ultrasound prostatic biopsy (TRUSPB) results, with an area under curve (AUC) value of 0.83±0.03. Therefore urinary Spm shows potential to serve as a novel PCa diagnostic biomarker, which in turn can help to address the limited sensitivity and specificity problem of serum PSA test.
| S-EPMC5012650 | biostudies-literature
Project description:BackgroundProstate cancer progresses slowly when present in low risk forms but can be lethal when it progresses to metastatic disease. A non-invasive test that can detect significant prostate cancer is needed to guide patient management.MethodsCapillary electrophoresis/mass spectrometry has been employed to identify urinary peptides that may accurately detect significant prostate cancer. Urine samples from 823 patients with PSA (<15 ng/ml) were collected prior to biopsy. A case-control comparison was performed in a training set of 543 patients (nSig = 98; nnon-Sig = 445) and a validation set of 280 patients (nSig = 48, nnon-Sig = 232). Totally, 19 significant peptides were subsequently combined by a support vector machine algorithm.ResultsIndependent validation of the 19-biomarker model in 280 patients resulted in a 90% sensitivity and 59% specificity, with an AUC of 0.81, outperforming PSA (AUC = 0.58) and the ERSPC-3/4 risk calculator (AUC = 0.69) in the validation set.ConclusionsThis multi-parametric model holds promise to improve the current diagnosis of significant prostate cancer. This test as a guide to biopsy could help to decrease the number of biopsies and guide intervention. Nevertheless, further prospective validation in an external clinical cohort is required to assess the exact performance characteristics.
| S-EPMC6738044 | biostudies-literature