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Circulating microRNAs combined with PSA for an accurate and non-invasive prostate cancer detection

ABSTRACT: Background: Early detection of prostate cancer (PCa) is limited by the lack of accurate non-invasive biomarkers easily evaluable in men within a screening context. Prostate-specific antigene (PSA) measurement leads to high percentages of both false positives and false negatives. In the era of liquid biopsies, we propose to combine PSA dosage with the evaluation of circulating microRNAs (miRs), to discriminate between men harbouring or not PCa. Methods: miR profiling of plasma samples from 60 men with PCa, 51 with benign prostatic hyperplasia (BPH) and 27 healthy donors (HD) was performed using microarrays. Univariate analysis (linear models with an empirical Bayes approach) and multivariate penalized logistic regression models were applied to highlight miRs and clinical variables associated with the presence of malignant disease, and were combined in a classification score. Finally, the developed score was tested on an independent dataset of 242 plasma samples (68 PCa, 8 premalignant lesions, 93 BPH, 73 HD), where miR expression was evaluated by RT-qPCR. Results: Out of 2006 miRs analyzed, a linear combination of miR-103a-3p and let-7a-5p with PSA defined our score. A classification rule based on this score allowed reclassification of samples with accuracy (0.61), sensitivity (0.87), specificity (0.35) and AUC (0.68) higher than those obtained by PSA alone. On the validation set, the same classification rule still performed better than PSA alone in terms of specificity (0.57 versus 0.55) and AUC (0.76 versus 0.74), allowing correct reclassification of all but one tumors not detected by PSA and 33% of BPH with PSA in the 4-16 ng/ml range. Conclusion: The combination of two circulating miRs with PSA could be an interesting biomarker to detect the presence of PCa (even when PSA levels are below the standard cut-off of 4 ng/ml) and the absence of PCa in an important fraction of men with high PSA, who may avoid unnecessary biopsies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE113234 | GEO | 2019/01/31

REPOSITORIES: GEO

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Project description:BACKGROUND: Noninvasive methods for the early identify diagnosis of prostatitis, benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are current clinical challenges.METHODS: The serum metabolites of 20 healthy individuals and patients with prostatitis, BPH, or PCa were identified using untargeted liquid chromatography-mass spectrometry (LC-MS).RESULTS: Organic acid metabolites had good sensitivity and specificity in differentiating prostatitis, BPH, and PCa. In addition, targeted LC-MS was used to verify the organic acid metabolites in the serum of a validation cohort. 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[1]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 (A UC=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. Targeted organic acid assay is reported in the current study MTBLS6038.Untargeted assay is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS6039' rel='noopener noreferrer' target='_blank'>MTBLS6039</a>.

Project description:BACKGROUND: Noninvasive methods for the early identify diagnosis of prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer (PCa) are current clinical challenges.METHODS: The serum metabolites of 20 healthy individuals and patients with prostatitis, BPH, or PCa were identified using untargeted liquid chromatography-mass spectrometry (LC-MS).RESULTS: Organic acid metabolites had good sensitivity and specificity in differentiating prostatitis, BPH, and PCa. In addition, targeted LC-MS was used to verify the organic acid metabolites in the serum of a validation cohort. 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 (A UC=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. Untargeted assay is reported in the current study MTBLS6039.Targeted organic acid assay is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS6038' rel='noopener noreferrer' target='_blank'>MTBLS6038</a>.

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Circulating microRNAs combined with PSA for an accurate and non-invasive prostate cancer detection

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