Clinical competence of serum miR-372 expression in diagnosing prostate cancer

2020 ◽  
Author(s):  
Sheng Li ◽  
Xiaolan Ruan ◽  
Tongzu Liu

Abstract Background: Prostate cancer (PCa) is considered as a serious healthy burden among males around the world. The limited diagnosis leads to poor outcomes of this malignancy. Aberrant expression of microRNAs (miRNAs) have been found in human cancers and play crucial roles in these malignant diseases. MicroRNA-372 (miR-372), as a type of miRNAs, has ever been investigated in various cancers. The purpose of the present study was to assess the expression patterns and diagnostic value of miR-372 in patients with PCa.Methods: 134 PCa patients and 68 healthy individuals were included in this study. The serum expression of miR-372 was examined by quantitative real-time PCR (qRT-PCR). To verify the diagnostic significance of miR-372, receiver operating characteristics (ROC) analysis was conducted for PCa patients.Results: Downregulated miR-372 expression was detected in serum samples collected from PCa patients compared with the healthy controls (P<0.001). The decreased expression of miR-372 was influenced by the positive lymph node metastasis (P=0.016), high prostate-specific antigen (PSA) concentration (P=0.002) and advanced TNM stage (P=0.013). The ROC curve was obtained with an AUC value of 0.896. At the cutoff value of 2.855, the sensitivity and specificity were 82.8% and 87.3%, respectively, suggesting the high diagnostic accuracy of miR-372.Conclusion: In summary, serum downregulated expression of miR-372 could serve as an efficient diagnostic biomarker for patients with PCa.

2019 ◽  
Vol 7 (10) ◽  
pp. 1628-1630 ◽  
Author(s):  
Kharisma Prasetya Adhyatma ◽  
Fauriski F. Prapiska ◽  
Ginanda Putra Siregar ◽  
Syah Mirsya Warli

BACKGROUND: Over the past decades, the study of the microenvironment of cancer has supported the hypothesis between inflammation and cancer. Previous studies have demonstrated a promising value of platelet-to-lymphocyte (PLR) and neutrophil-to-lymphocyte ratio (NLR) as a systemic inflammatory response in prostate cancer. AIM: To evaluate their pre-biopsy values of PLR and NLR in predicting prostate cancer. MATERIAL AND METHODS: This is a diagnostic study with retrospective design. We included all benign prostatic hyperplasia (BPH) and prostate cancer (PCa) patients who underwent prostate biopsy in Adam Malik Hospital between August 2011 and August 2015. We used PSA value above 4 ng/dL as the threshold for the biopsy candidates. The relationship between pre-biopsy variables affecting the percentage of prostate cancer risk was evaluated, including age, prostate-specific antigen (PSA) level, and estimated prostate volume (EPV). The PLR and NLR were calculated from the ratio of related platelets or absolute neutrophil counts with their absolute lymphocyte counts. The values then analysed to evaluate their associations with the diagnosis of BPH and PCa. RESULTS: Out of 298 patients included in this study, we defined two groups consist of 126 (42.3%) BPH and 172 PCa (57.7%) patients. Mean age for both groups are 66.36 ± 7.53 and 67.99 ± 7.48 years old (p = 0.64), respectively. There are statistically significant differences noted from both BPH and PCa groups in terms of PSA (19.28 ± 27.11 ng/dL vs 40.19 ± 49.39 ng/dL), EPV  (49.39 ± 23.51 cc vs 58.10 ± 30.54 cc), PLR (160.27 ± 98.96 vs 169.55 ± 78.07), and NLR (3.57 ± 3.23 vs 4.22 ± 2.59) features of both BPH and PCa groups respectively (p < 0.05). A Receiver Operating Characteristics (ROC) analysis was performed for PLR and NLR in analysing their value in predicting prostate cancer. The Area Under the Curve (AUC) of PLR is 57.9% with a sensitivity of 56.4% and specificity of 55.6% in the cut-off point of 143 (p = 0.02). The NLR cut-off point of 3.08 gives 62.8% AUC with 64.5% sensitivity and 63.5% specificity. These AUCs were comparable with the AUC of PSA alone (68.5%). We performed logistic regression between PSA, PLR, and NLR with result in the exclusion of PLR if calculated conjunctively. Therefore, NLR has a promising performance in predicting PCa in patients with PSA above 4 ng/dL (OR = 3.2; 95% CI: 1.96-5.11). We found as many as 80 (63.5%) patients with benign biopsy results with negative NLR value in this study. CONCLUSION: NLR has promising value in predicting prostate cancer. A further prospective study in validating its diagnostic value was needed.


MicroRNA ◽  
2020 ◽  
Vol 09 ◽  
Author(s):  
Yakup Dülgeroğlu ◽  
Onur Eroğlu

Introduction: Prostate cancer (PCa) is the second most common cancer in males and is at fifth place in cancerassociated mortality. Although the prostate-specific antigen (PSA) test is widely used in PCa screenings, it has significant limitations in the differential diagnosis of PCa. Therefore, studies on developing new biomarkers on PCa diagnosis are ongoing. miRNAs are good candidate biomarkers for the diagnosis of cancers, including prostate cancer, as they can be easily detected from the circulation. Objective: In this study, it is aimed to determine diagnostic value of serum levels of miR-223-3p and -223-5p in benign prostate hyperplasia (BPH), chronic prostatitis (CP) and prostate cancer (PCa). Methods: Serum samples was collected from 68 patients in total (25 BPH, 10 CP, 33 PCa). miR-223-3p and -223-5p levels were measured in serum with qRT-PCR. The Ct values of miRNAs were normalized according to the Ct value of ce-miR-39 and calculated -ΔCt values were used statistical analyses. Results: The serum levels of miR-223-3p and -223-5p were downregulated in the PCa and CP groups, compared to the BPH group. There was no statistically significant difference between PCa and CP groups. The sensitivity and specificity of miR-223-3p, -223-5p and their combination were calculated as 88% and 88%; 86% and 79%; 93% and 92% in discriminating BPH and PCa groups, respectively. Conclusion: In this study, it was shown that miR-223-3p and -223-5p were both detectable in the circulation. miR-223- 3p, -223-5p, and their combination may be good candidate biomarkers for prostate cancer diagnosis. Also, observation of similar serum levels of miR-223-3p and -223-5p between CP and PCa groups suggests that miR-223 may play a role in prostate cancer development originated from chronic inflammation.


2004 ◽  
Vol 50 (9) ◽  
pp. 1607-1617 ◽  
Author(s):  
Ville Väisänen ◽  
Susann Eriksson ◽  
Kaisa K Ivaska ◽  
Hans Lilja ◽  
Martti Nurmi ◽  
...  

Abstract Background: Free and total human kallikrein 2 (hK2) might improve the discrimination between prostate cancer and benign prostatic hyperplasia. Concentrations of hK2 are 100-fold lower than concentrations of prostate-specific antigen (PSA); therefore, an hK2 assay must have a low detection limit and good specificity. Methods: PSA- and hK2-specific monoclonal antibodies were used in solid-phase, two-site immunofluorometric assays to detect free and total hK2. The total hK2 assay used PSA-specific antibodies to block nonspecific signal. The capture antibody of the free hK2 assay did not cross-react with PSA. To determine the hK2 concentrations in the male bloodstream, total hK2 was measured in a control group consisting of 426 noncharacterized serum samples. Free and total hK2 were measured in plasma from 103 patients with confirmed prostate cancer. Results: All 426 males in the control group had a total hK2 concentration above the detection limit of 0.0008 μg/L. The median total hK2 concentration was 0.022 μg/L (range, 0.0015–0.37 μg/L). hK2 concentrations were 0.1–58% of total PSA (median, 3.6%). hK2 concentrations were similar in men 41–50 and 51–60 years of age. The ratio of hK2 to PSA steadily decreased from 5–30% at PSA &lt;1 μg/L to 1–2% at higher PSA concentrations. In 103 patients with prostate cancer, the median hK2 concentration in plasma was 0.079 μg/L (range, 0.0015–16.2 μg/L). The median free hK2 concentration was 0.070 (range, 0.005–12.2) μg/L. The proportion of free to total hK2 varied from 17% to 131% (mean, 85%). Conclusions: The wide variation in the free-to-total hK2 ratio suggests that hK2 in blood plasma is not consistently in the free, noncomplexed form in patients with prostate cancer. The new assay is sufficiently sensitive to be used to study the diagnostic accuracies of free and total hK2 for prostate cancer.


2013 ◽  
Vol 59 (10) ◽  
pp. 1514-1522 ◽  
Author(s):  
Morteza Razavi ◽  
Lisa DS Johnson ◽  
Julian J Lum ◽  
Gary Kruppa ◽  
N Leigh Anderson ◽  
...  

BACKGROUND Biomarker validation remains one of the most challenging constraints to the development of new diagnostic assays. To facilitate biomarker validation, we previously developed a chromatography-free stable isotope standards and capture by antipeptide antibodies (SISCAPA)-MALDI assay allowing rapid, high-throughput quantification of protein analytes in large sample sets. Here we applied this assay to the measurement of a surrogate proteotypic peptide from protein C inhibitor (PCI) in sera from patients with prostate cancer. METHODS A 2-plex SISCAPA-MALDI assay for quantification of proteotypic peptides from PCI and soluble transferrin receptor (sTfR) was used to measure these peptides in 159 trypsin-digested sera collected from 51 patients with prostate cancer. These patients had been treated with radiation with or without neoadjuvant androgen deprivation. RESULTS Patients who experienced biochemical recurrence of prostate cancer showed decreased serum concentrations of the PCI peptide analyte within 18 months of treatment. The PCI peptide concentrations remained increased in the sera of patients who did not experience cancer recurrence. Prostate-specific antigen concentrations had no predictive value during the same time period. CONCLUSIONS The high-throughput, liquid chromatography–free SISCAPA-MALDI assay is capable of rapid quantification of proteotypic PCI and sTfR peptide analytes in complex serum samples. Decreased serum concentrations of the PCI peptide were found to be related to recurrence of prostate cancer in patients treated with radiation with or without hormone therapy. However, a larger cohort of patients will be required for unequivocal validation of the PCI peptide as a biomarker for clinical use.


2002 ◽  
Vol 48 (8) ◽  
pp. 1272-1278 ◽  
Author(s):  
Barbara R Grzeda ◽  
Tuan Le Bui ◽  
Cheryl N Warner ◽  
Tracy L Pirucki ◽  
Lisa M Dewey ◽  
...  

Abstract Background: Prostate-specific antigen (PSA) is widely used in the detection and monitoring of prostate cancer. We developed a system for the self-collection and transport of capillary whole blood for PSA analysis, with the goal of reducing phlebotomy visits and, thus, increasing the access and utilization of PSA in prostate cancer screening and monitoring. Methods: The blood collection device [BIOSAFE Blood Transport System (BTSTM)] collects 70 μL of blood through a heparin-coated material into 200 μL of stabilizing solution. The diluted whole blood is used for measurement of PSA by a modified version of the Hybritech® Tandem-MP PSA Assay. Results were compared for matched samples of professionally and self-collected BTS blood and for matched BTS samples sera from blood collected by venipuncture. Imprecision for the whole-blood PSA measurement was estimated from analysis of whole-blood controls in duplicate, twice per day, over 20 days. Results: BTS samples (n = 140) collected by a qualified healthcare professional compared with serum samples yielded the regression equation: y =1.02x + 0.04 (Sy|x = 0.35; r = 0.99). Comparison of the results for samples (n = 128) collected by the patient without professional assistance with serum samples yielded: y = 1.08x + 0.02 (Sy|x = 0.31; r = 0.99). The between-run CVs at 0.069, 0.53, 2.9, and 10.7 μg/L were 21%, 6.0%, 3.5%, and 3.8%, respectively. PSA was stable in BTS samples stored for 21 days at 18–24 °C and for 7 days at 37 °C. Conclusion: The BIOSAFE BTS system allows accurate and convenient measurement of circulating PSA by a precise method for diluted whole blood.


2018 ◽  
Vol 33 (3) ◽  
pp. 275-282 ◽  
Author(s):  
Martin Boegemann ◽  
Christian Arsov ◽  
Boris Hadaschik ◽  
Kathleen Herkommer ◽  
Florian Imkamp ◽  
...  

Introduction: Total PSA (tPSA) and free PSA (fPSA) are the most commonly used biomarkers for early detection of prostate cancer. Despite standardization efforts, many available PSA assays may still produce discordant results. In the present study, we compared four PSA assays calibrated to the WHO standards 96/670 and 96/668 for tPSA and fPSA, respectively. Methods: Within the scope of the Prostate Cancer Early Detection Study Based on a ‘‘Baseline’’ PSA Value in Young Men (PROBASE), we tested tPSA and fPSA in serum samples from 50 patients in the four different PROBASE sites using four WHO-calibrated assays from Roche (Elecsys, Cobas), Beckman-Coulter (Access-II) and Siemens (ADVIA Centaur). The comparison was performed using the Passing–Bablok regression method. Results: Compared to Access, the median tPSA levels for Centaur, Elecsys, and Cobas were +3%, +11%–20%, and +17%–23%, respectively, while for median fPSA levels the differences for Centaur, Elecsys, and Cobas were +49%, +29%–31%, and +22%, respectively. Discussion: Despite all investigated assays being WHO-calibrated, the Elecsys and Cobas tPSA assays produced considerably higher results than the Access and Centaur assays. Differences in fPSA-recovery between all investigated assays were even more pronounced. When applying the tPSA cutoff of 3.1 μg/L recommended for WHO-calibrated assays, the use of higher calibrated assays may lead to unnecessary prostate biopsies. Conversely, if the historical threshold of 4 μg/L is applied when using WHO-calibrated assays, it could lead to falsely omitted prostate biopsies.


2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Changqing Yin ◽  
Changliang Luo ◽  
Wei Hu ◽  
Xu Ding ◽  
Chunhui Yuan ◽  
...  

As part of “liquid biopsy,” lots of literature indicated the potential diagnostic value of circulating cell-free DNA (cfDNA) in the management of prostate cancer (PCa). However, the literature on the accuracy of cfDNA detection in PCa has been inconsistent. Hence, we performed this meta-analysis to assess the diagnostic value of cfDNA in PCa. A total of 19 articles were included in this analysis according to the inclusion and exclusion criteria. We then investigated two main subgroups in this meta-analysis, including qualitative analysis of abnormal level of cfDNA and qualitative analysis of single-gene methylation alterations. Overall, the results of quantitative analysis showed sensitivity of 0.73 (95% CI, 0.62–0.82) and specificity of 0.80 (95% CI, 0.70–0.87), with an area under the curve (AUC) of 0.83 (95% CI, 0.80–0.86). For qualitative assessment, the values were 0.34 (95% CI, 0.22–0.48), 0.99 (95% CI, 0.97–1.00), and 0.91 (95% CI, 0.88–0.93), respectively. Our results suggest the pooled specificity of each subgroup is much higher than the specificity of prostate-specific antigen (PSA). However, they are not recommended for PCa screening alone, because their sensitivities are not higher than the conventional serum biomarkers PSA. We conclude that analysis of cfDNA can be used as an adjuvant tool for PCa screening.


Author(s):  
Xavier Filella ◽  
Laura Foj

AbstractmicroRNAs (miRNAs) are small non-coding RNAs that control gene expression posttranscriptionally and are part of the giant non codifying genoma. Cumulating data suggest that miRNAs are promising potential biomarkers for many diseases, including cancer. Prostate cancer (PCa) detection is currently based in the serum prostate-specific antigen biomarker and digital rectal examination. However, these methods are limited by a low predictive value and the adverse consequences associated with overdiagnosis and overtreatment. New biomarkers that could be used for PCa detection and prognosis are still needed. Recent studies have demonstrated that aberrant expressions of microRNAs are associated with the underlying mechanisms of PCa. This review attempts to extensively summarize the current knowledge of miRNA expression patterns, as well as their targets and involvement in PCa pathogenesis. We focused our review in the value of circulating and urine miRNAs as biomarkers in PCa patients, highlighting the existing discrepancies between different studies, probably associated with the important methodological issues related to their quantitation and normalization. The majority of studies have been performed in serum or plasma, but urine obtained after prostate massage appears as a new way to explore the usefulness of miRNAs. Large screening studies to select a miRNA profile have been completed, but bioinformatics tools appear as a new approach to select miRNAs that are relevant in PCa development. Promising preliminary results were published concerning miR-141, miR-375 and miR-21, but larger and prospective studies using standardized methodology are necessary to define the value of miRNAs in the detection and prognosis of PCa.


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