Clinical utility of a serum biomarker panel in distinguishing prostate cancer from benign prostate hyperplasia.
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ABSTRACT:
SUBMITTER: Kiebish MA
PROVIDER: S-EPMC8302659 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The study aim was to identify novel serum markers of prostate cancer diagnosis compared to benign prostate hyperplasia and healthy controls
2016-10-04 | PXD004575 | Pride
Project description:BackgroundProstate Cancer (PCa) represents the second leading cause of cancer-related death in men. Prostate-specific antigen (PSA) serum testing, currently used for PCa screening, lacks the necessary sensitivity and specificity. New non-invasive diagnostic tools able to discriminate tumoral from benign conditions and aggressive (AG-PCa) from indolent forms of PCa (NAG-PCa) are required to avoid unnecessary biopsies.MethodsIn this work, 32 formerly N-glycosylated peptides were quantified by PRM (parallel reaction monitoring) in 163 serum samples (79 from PCa patients and 84 from individuals affected by benign prostatic hyperplasia (BPH)) in two technical replicates. These potential biomarker candidates were prioritized through a multi-stage biomarker discovery pipeline articulated in: discovery, LC-PRM assay development and verification phases. Because of the well-established involvement of glycoproteins in cancer development and progression, the proteomic analysis was focused on glycoproteins enriched by TiO2 (titanium dioxide) strategy.ResultsMachine learning algorithms have been applied to the combined matrix comprising proteomic and clinical variables, resulting in a predictive model based on six proteomic variables (RNASE1, LAMP2, LUM, MASP1, NCAM1, GPLD1) and five clinical variables (prostate dimension, proPSA, free-PSA, total-PSA, free/total-PSA) able to distinguish PCa from BPH with an area under the Receiver Operating Characteristic (ROC) curve of 0.93. This model outperformed PSA alone which, on the same sample set, was able to discriminate PCa from BPH with an AUC of 0.79. To improve the clinical managing of PCa patients, an explorative small-scale analysis (79 samples) aimed at distinguishing AG-PCa from NAG-PCa was conducted. A predictor of PCa aggressiveness based on the combination of 7 proteomic variables (FCN3, LGALS3BP, AZU1, C6, LAMB1, CHL1, POSTN) and proPSA was developed (AUC of 0.69).ConclusionsTo address the impelling need of more sensitive and specific serum diagnostic tests, a predictive model combining proteomic and clinical variables was developed. A preliminary evaluation to build a new tool able to discriminate aggressive presentations of PCa from tumors with benign behavior was exploited. This predictor displayed moderate performances, but no conclusions can be drawn due to the limited number of the sample cohort. Data are available via ProteomeXchange with identifier PXD035935.
| S-EPMC10662699 | biostudies-literature
Project description:Metalloproteinases (MMPs) are involved in metastatic tumor processes, with changes in circulating levels detected in several cancer types. Here, we compare serum concentrations of metalloproteinase-1 (MMP-1) across individuals clinically diagnosed with prostate cancer (PCa) or benign prostatic hyperplasia (BPH), correcting results for the rs495366 single nucleotide polymorphism (SNP) that predisposes to differential MMP-1 levels. 196 men aged ≥50 years were followed at a university hospital urology outpatient clinic, with clinical, anthropometric, and rectal examinations performed by one urologist. Blood samples obtained prior to any clinical intervention provided baseline MMP-1 and total/free PSA levels as well as metabolic, hormonal, and inflammatory markers. The SNP was genotyped by real-time PCR. Participants with medical and/or laboratory profile compatible with malignancy composed the PCa group when confirmed by the Gleason scale. As expected, A-allele homozygotes showed reduced levels of MMP-1. Genotype-adjusted analyses revealed the mean MMP-1 level as 2-fold higher in PCa carriers compared to BPH patients. No other differences were found according to the prostatic condition or genotypic distribution, except for the expected raise in total and free PSA levels in PCa. In conclusion, increased serum levels of MMP-1 were observed in this context of prostatic malignancy compared to a benign phenotype, regardless of a genetic influence.
| S-EPMC7222547 | biostudies-literature
Project description:MicroRNAs (miRNAs) are a class of short (~22nt), single stranded RNA molecules that function as post-transcriptional regulators of gene expression. MiRNAs can regulate a variety of important biological pathways, including: cellular proliferation, differentiation and apoptosis. Profiling of miRNA expression patterns was shown to be more useful than the equivalent mRNA profiles for characterizing poorly differentiated tumours. As such, miRNA expression "signatures" are expected to offer serious potential for diagnosing and prognosing cancers of any provenance. The aim of this study was to investigate the potential of using deregulation of urinary miRNAs in order to detect Prostate Cancer (PCa) among Benign Prostatic Hyperplasia (BPH). To identify the miRNA signatures specific for PCa, miRNA expression profiling of 8 PCa patients, 12 BPH patients and 10 healthy males was carried out using whole genome expression profiling. Differential expression of two individual miRNAs between healthy males and BPH patients was detected and found to possibly target genes related to PCa development and progression. The sensitivity and specificity of miR-1825 for detecting PCa among BPH individuals was found to be 60% and 69%, respectively. Whereas, the sensitivity and specificity of miR-484 were 80% and 19%, respectively. Additionally, the sensitivity and specificity for miR-1825/484 in tandem were 45% and 75%, respectively. The proposed PCa miRNA signatures may therefore be of great value for the accurate diagnosis of PCa and BPH. This exploratory study has identified several possible targets that merit further investigation towards the development and validation of diagnostically useful, non-invasive, urine-based tests that might not only help diagnose PCa but also possibly help differentiate it from BPH.
| S-EPMC3931266 | biostudies-literature
Project description:ObjectivesTo identify and validate a biomarker panel by serum metabolic profiling for improvement of PCa diagnosis.Materials and methodsTotally, 134 individuals were included in this study. Among them, 39 PCa patients and 45 control patients (negative prostate biopsy) were involved in the discovery phase and 50 healthy controls were enrolled for validation phase of metabolomics study. LC-MS Analysis was used for the identification of the serum metabolites of patients.ResultsLogistics regression analysis shows that 5 metabolites [dMePE(18:0/18:2), PC(16:0/20:2), PS(15:0/18:2), SM(d16:0/24:1], Carnitine C14:0) were significantly changed in PCa patients compared with control patients. A metabolic panel (MET) was calculated, showing a significantly higher diagnostic performance than PSA in differentiating PCa from control patients [AUC (MET vs. PSA): 0.823 ± 0.046 vs. 0.712 ± 0.057, p<0.001]. Moreover, this panel was superior to PSA in distinguishing PCa from negative prostate biopsies when PSA levels were less than 20 ng/ml [AUC (MET vs. PSA]: 0.836 ± 0.050 vs. 0.656 ± 0.067, p<0.001]. In the validation set, the MET panel yielded an AUC of 0.823 in distinguishing PCa patients from healthy controls, showing a significant improvement of PCa detection.ConclusionsThe metabolite biomarker panel discovered in this study presents a good diagnostic performance for the detection of PCa.
| S-EPMC8138432 | biostudies-literature
Project description:Bladder outlet obstruction (BOO) in large and small prostates is managed in a similar manner despite considerably different pathophysiology, which can result in higher failure rates. We investigate the clinical and urodynamic features and study the outcome of patients with benign prostate hyperplasia (BPH) according to their prostate size.We prospectively analyzed 100 BPH patients undergoing urodynamic study between January 2015 and August 2016 and divided them into two groups according to their prostate size: small (≤30 mL) and large prostate (>30 mL) groups. We compared the groups regarding age, International Prostate Symptom Score, maximal flow rate (Qmax), postvoided residual, serum prostate-specific antigen (PSA), prostate volume measured by ultrasonography (USG), and urodynamic findings.For testing the hypothesis, we used the Chi-square test, Student's t-test, and one-way analysis of variance when comparing between groups and conducted the logistic regression analysis for determining predictive factors of BOO.Although the total prostate volume significantly correlated with the PSA, patients with a small prostate had lower Qmax (5.27 ± 4.8 mL/s vs. 6.14 ± 6.66 mL/s; P = 0.74), higher incidence of abnormal baldder capacity (39.9% vs. 31.25%), lower voiding efficiency (39.3 ± 40.5% vs. 40.57 ± 32.11%), low compliance (44.4% vs. 31.3%), higher incidence of indeterminate detrusor contractions (38.9% vs. 37.5%), lower incidence of detrusor underactivity (33.3% vs. 28.1%), lower BOO index (40.9 ± 43.2 vs. 49.10 ± 44.48), lower bladder contractility index (77.8 ± 48.84 vs. 92.09 ± 52.79), and lower PdetQmax (51.44 ± 42.23 vs. 61.38 ± 42.01 cmH2O). Small prostates had higher failed voiding trials postsurgery.BOO patients with a small prostate showed poor urodynamic parameters and reported higher postoperative complications.
| S-EPMC5532887 | biostudies-other
Project description:Papillary thyroid carcinoma (PTC) is the most common endocrine cancer with a significantly increase of the incidence recently. Several cytokines, such as thyroid peroxidase (TPO), cluster of differentiation 56 (CD56), Galectin-3, mesothelial cell (MC), cytokeratin 19 (CK19) and BRAF (B-raf) were recommended to be tested by immunohistochemistry (IHC) for a definitive diagnosis, but were still limited in clinical use because of their relative lower sensitivity and specificity. MicroRNA (miRNA), as a new molecular biomarkers, however, has not been reported yet so far. To address this, hsa-miR-200a-5p, a miRNA, was selected and detected in PTC patients by in situ hybrization with benign thyroid tumor with papillary hyperplasia as a control, and the differential expression of hsa-miR-200a-5p between fresh PTC tissues and control was detected by qRT-PCR. Expressive levels of cytokines of TPO, CD56, Galectin-3, MC, CK19 and B-raf were also detected by immunohistochemistry. The correlation was analyzed by SPSS software using Spearman methods. As expected, the hsa-miR-200a-5p expressive level was significantly increased in PTC patients, compared to that of control, and was consistent with that of TPO, CD56, Galectin-3, MC, CK19 and B-raf. In addition, expression of hsa-miR-200a-5p showed negative correlation to that of TPO (rs = - 0.734; **: P < 0.01) and CD56 (rs = - 0.570; **: P < 0.01), but positive correlation to that of Galectin-3 (rs = 0.601; **: P < 0.01), MC (rs = 0.508; **: P < 0.01), CK19 (rs = 0.712; **: P < 0.01) and B-raf (rs = 0.378; **: P < 0.01). PTC and papillary benign thyroid papillary hyperplasia are difficult to distinguish in morphology, so requiring immunohistochemistry to further differentiate the diagnosis, however, for the existing clinical common diagnostic marker for immunohistochemistry, the sensitivity and accuracy are low, it is easy to miss diagnosis. Therefore, there is an urgent need for a rapid and sensitive molecular marker. So miR-200a-5p can be used to assist in the diagnosis of PTC at the molecular level, and as a biomarker, can be effectively used to distinguish between PTC and benign thyroid tumor with papillary hyperplasia.
| S-EPMC6044525 | biostudies-literature
Project description:It is well known that prostate cancer (PCa) is a progressive disease involving multiple gene alterations. The Gleason score (GS) is a morphologic feature of PCa used in the clinic to evaluate the risk of disease progression. However, GS often fail to clearly distinguish between indolent and aggressive disease. The aim of this study was to identify potential biomarkers for PCa risk stratification. An in-depth proteomics analysis (LC ESI-MS/MS) was performed on human PCa and BPH tissues. First, we identified differentially expressed proteins between PCa and BPH samples. We then filtered the proteins based on peptide spectrum matches and selected a panel of candidates. To assess and validate the clinical significance of these peptides we performed an integrative bioinformatics analysis using public database repositories. We identified YWHAZ, an androgen receptor downstream target, as one of the proteins enriched in PCa compared with BPH. We also found a strong association of YWHAZ expression with poor prognosis across different PCa datasets. Briefly, overall and relapse-free survival were significantly shorter in PCa cases expressing high vs. low YWHAZ expression. Further, multivariate analyses displayed high significant correlation with poor prognosis, independent from GS, age, PSA at diagnosis and TMPRSS2-ERG fusion. A multi-cancer screening for YWHAZ unveils amplification as the main alteration for this gene correlating with increased mRNA expression levels across all types of cancer through the cBioPortal platform. YWHAZ rises as a promising prognostic factor in PCa, independent from GS, aiding in disease risk stratification.
2021-09-08 | PXD014291 | Pride
Project description:BackgroundNoninvasive methods for the early identify diagnosis of prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer (PCa) are current clinical challenges.MethodsThe serum metabolites of 20 healthy individuals and patients with prostatitis, BPH, or PCa were identified using untargeted liquid chromatography-mass spectrometry (LC-MS). In addition, targeted LC-MS was used to verify the organic acid metabolites in the serum of a validation cohort.ResultsOrganic acid metabolites had good sensitivity and specificity in differentiating prostatitis, BPH, and PCa. Three diagnostic models identified patients with PROSTATITIS: phenyllactic acid (area under the curve [AUC]=0.773), pyroglutamic acid (AUC=0.725), and pantothenic acid (AUC=0.721). Three diagnostic models identified BPH: citric acid (AUC=0.859), malic acid (AUC=0.820), and D-glucuronic acid (AUC=0.810). Four diagnostic models identified PCa: 3-hydroxy-3-methylglutaric acid (AUC=0.804), citric acid (AUC=0.918), malic acid (AUC=0.862), and phenyllactic acid (AUC=0.713). Two diagnostic models distinguished BPH from PCa: phenyllactic acid (AUC=0.769) and pyroglutamic acid (AUC=0.761). Three diagnostic models distinguished benign BPH from PROSTATITIS: citric acid (AUC=0.842), ethylmalonic acid (AUC=0.814), and hippuric acid (AUC=0.733). Six diagnostic models distinguished BPH from prostatitis: citric acid (AUC=0.926), pyroglutamic acid (AUC=0.864), phenyllactic acid (AUC=0.850), ethylmalonic acid (AUC=0.843), 3-hydroxy-3-methylglutaric acid (AUC=0.817), and hippuric acid (AUC=0.791). Three diagnostic models distinguished PCa patients with PROSTATITISA < 4.0 ng/mL from those with PSA > 4.0 ng/mL: 5-hydromethyl-2-furoic acid (AUC=0.749), ethylmalonic acid (AUC=0.750), and pyroglutamic acid (AUC=0.929). Conclusions: These results suggest that serum organic acid metabolites can be used as biomarkers to differentiate prostatitis, BPH, and PCa.
| S-EPMC9846500 | biostudies-literature
Project description:IntroductionPlatelet indices changes in severely ill people and in dogs with inflammation are compatible findings. This study aimed to compare platelet indices between dogs with clinical benign prostatic hyperplasia (BPH) and healthy controls. Additionally, to determine whether there is a correlation between the relative prostatic size (S rel) and the platelet indices in BPH dogs.MethodsThirty-five adult intact male dogs of different breeds were allocated to the experimental groups: dogs with clinical BPH (groups A; n = 24; median age of 6 years; the median weight of 8.50 kg) and healthy dogs (group B; n = 11; median age 5.50 years; the median weight of 7.00 kg) based on physical examination, clinical signs, and S rel detected by ultrasonographic findings. The individual prostatic volume (IPV) was divided by the expected prostatic volume (EPV) to determine the relative prostatic size in dogs over 4 years old. Platelet indices were compared between the two groups, and a correlation between S rel and these indices was calculated.ResultsThe median S rel of dogs in group A was significantly higher (P = 0.001), and the mean plateletcrit (PCT) was significantly lower (P = 0.003) compared with those in group B. S rel showed a significant negative correlation with PLT and PCT (r = -0.388; P = 0.02 and r = -0.402; P = 0.01). Receiver operating characteristic (ROC) analysis showed PLT and PCT thresholds for estimating S rel > 1 with 75% and 87.5% sensitivity and 71.82 and 63.64% specificity.DiscussionThe findings of this study support the use of platelet indices like PLT and PCT to detect clinical BPH in dogs. However, more research is needed to confirm their utility in conjunction with other previously described diagnostic factors.
| S-EPMC9772470 | biostudies-literature