scholarly journals Circulating miRNAs as Biomarkers for Prostate Cancer Diagnosis in Subjects with Benign Prostatic Hyperplasia

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Wei Jin ◽  
Xiang Fei ◽  
Xia Wang ◽  
Fangjie Chen ◽  
Yan Song

Body fluids often contain freely circulating nucleic acids, many of which can be exploited as noninvasive tools for the diagnosis of cancer as well as for clinical prognostication. Identifying microRNAs (miRNAs) in subjects’ blood with various malignancies means that they can serve as novel biomarkers for prostate cancer (PCa) diagnosis. This study analyzed serum-circulating miRNAs as a noninvasive biomarker in subjects with PCa and subjects with benign prostatic hyperplasia (BPH). In total, 31 PCa subjects and 31 BPH subjects were included, with the BPH group serving as the control group. RT-qPCR was used to quantify the levels of 10 miRNAs, which included miR-18a, miR-34a, miR-106b, miR-183, miR-200a, miR-301a, miR-141, miR-182, miR-200b, and miR-375 in serum. Statistical tests were used to assess the relationship between the levels of miRNAs and the clinicopathological data. A significant increase was observed in the relative expression ratios of miR-141, miR-182, miR-200b, and miR-375 (1.89-, 2.09-, 2.41-, and 2.27-folds, respectively) in the PCa group when compared to the BPH group. Based on the receiver operating characteristic (ROC) analysis, the largest area under the curve (AUC), 0.923, was associated with the miR-200b group, indicating effective diagnostic properties for this biomarker. A correlation was observed between total prostate-specific antigen (TPSA) and the relative levels of miR-141, miR-182, miR-200b, and miR-375. The Gleason score and the miR-200b expression level were also correlated. These results are consistent with previous studies regarding the possibility of differentiating between PCa subjects and healthy controls based on the detection of miRNA. The findings attest to a distinctive expression profile of miRNA that is detectable in the blood of PCa subjects, thereby confirming the role of miRNAs as diagnostic biomarkers for PCa.

1999 ◽  
Vol 45 (11) ◽  
pp. 1960-1966 ◽  
Author(s):  
Angeliki Magklara ◽  
Andreas Scorilas ◽  
William J Catalona ◽  
Eleftherios P Diamandis

Abstract Background: Prostate-specific antigen (PSA) is the most reliable tumor marker available and is widely used for the diagnosis and management of prostate cancer. Unfortunately, PSA cannot distinguish efficiently between benign and malignant disease of the prostate, especially within the range of 4–10 μg/L. Among the refinements developed to enhance PSA specificity is the free/total PSA ratio, which is useful in discriminating between the two diseases within the diagnostic “gray zone”. Recent data indicate that human glandular kallikrein (hK2), a protein with high homology to PSA, may be an additional serum marker for the diagnosis and monitoring of prostate cancer. Methods: We analyzed 206 serum samples (all before treatment was initiated) from men with histologically confirmed benign prostatic hyperplasia (n = 100) or prostatic carcinoma (n = 106) with total PSA in the range of 2.5–10 μg/L. Total and free PSA and hK2 were measured with noncompetitive immunological procedures. Statistical analysis was performed to investigate the potential utility of the various markers or their combinations in discriminating between benign prostatic hyperplasia and prostatic carcinoma. Results: hK2 concentrations were not statistically different between the two groups of patients. There was a strong positive correlation between hK2 and free PSA in the whole patient population. hK2/free PSA ratio (area under the curve = 0.69) was stronger predictor of prostate cancer than the free/total PSA ratio (area under the curve = 0.64). At 95% specificity, the hK2/free PSA ratio identified 30% of patients with total PSA between 2.5–10 μg/L who had cancer. At 95% specificity, the hK2/free PSA ratio identified 25% of patients with total PSA between 2.5 and 4.5 μg/L who had cancer. Conclusions: Our data suggest that hK2 in combination with free and total PSA can enhance the biochemical detection of prostate cancer in patients with moderately increased total PSA concentrations. More specifically, the hK2/free PSA ratio appears to be valuable in identifying a subset of patients with total PSA between 2.5 and 4.5 μg/L who have high probability of cancer and who should be considered for biopsy.


2019 ◽  
Vol 14 (5) ◽  
pp. 1934578X1984997 ◽  
Author(s):  
Neil MacKinnon ◽  
Wencheng Ge ◽  
Peisong Han ◽  
Javed Siddiqui ◽  
John T. Wei ◽  
...  

Detection of prostate cancer (PCa) and distinguishing indolent versus aggressive forms of the disease is a critical clinical challenge. The current clinical test is circulating prostate-specific antigen levels, which faces particular challenges in cancer diagnosis in the range of 4 to 10 ng/mL. Thus, a concerted effort toward building a noninvasive biomarker panel has developed. In this report, the hypothesis that nuclear magnetic resonance (NMR)-derived metabolomic profiles measured in the urine of biopsy-negative versus biopsy-positive individuals would nominate a selection of potential biomarker signals was investigated. 1H NMR spectra of urine samples from 317 individuals (111 biopsy-negative, 206 biopsy-positive) were analyzed. A double cross-validation partial least squares-discriminant analysis modeling technique was utilized to nominate signals capable of distinguishing the two classes. It was observed that after variable selection protocols were applied, a subset of 29 variables produced an area under the curve (AUC) value of 0.94 after logistic regression analysis, whereas a “master list” of 18 variables produced a receiver operating characteristic ROC) AUC of 0.80. As proof of principle, this study demonstrates the utility of NMR-based metabolomic profiling of urine biospecimens in the nomination of PCa-specific biomarker signals and suggests that further investigation is certainly warranted.


2002 ◽  
Vol 48 (8) ◽  
pp. 1251-1256 ◽  
Author(s):  
Manuel Martínez ◽  
Francisco España ◽  
Montserrat Royo ◽  
José M Alapont ◽  
Silvia Navarro ◽  
...  

Abstract Background: The aim of this study was to assess the diagnostic accuracy of the proportion of prostate-specific antigen (PSA) complexed to α1-antichymotrypsin (PSA-α1ACT:PSA ratio) in the differential diagnosis of prostate cancer (CaP) and benign prostatic hyperplasia (BPH) in men with total PSA of 10–30 μg/L. Methods: We used our immunoassays (ELISAs) for total PSA and PSA-α1ACT complex to study 146 men. In 123, total PSA was between 10 and 20 μg/L; 66 of these had CaP and 57 BPH. In 23 men, total PSA was between 20 and 30 μg/L; 14 of these had CaP and 9 BPH. We calculated the area under the ROC curves (AUC) for total PSA, PSA-α1ACT complex, and PSA-α1ACT:PSA ratio, and determined the cutoff points that gave sensitivities approaching 100%. Results: In the total PSA range between 10 and 20 μg/L, the AUC was significantly higher for the PSA-α1ACT:PSA ratio (0.850) than for total PSA (0.507) and PSA-α1ACT complex (0.710; P <0.0001). A cutoff ratio of 0.62 would have permitted diagnosis of all 66 patients with CaP (100% sensitivity) and avoided 19% of unnecessary biopsies (11 of 57 patients). In the total PSA range between 20 and 30 μg/L, the AUC for the PSA-α1ACT:PSA ratio (0.980; 95% confidence interval, 0.82–0.99) was greater than the AUC for total PSA (0.750; 95% confidence interval, 0.51–0.89; P = 0.042). In this range, a cutoff point of 0.64 would have permitted the correct diagnosis of all 14 patients with CaP and 6 of the 9 with BPH. Conclusions: The diagnostic accuracy of the PSA-α1ACT:PSA ratio persists at high total PSA concentrations, increasing the specificity of total PSA. Prospective studies with large numbers of patients are needed to assess whether the ratio of PSA-α1ACT to total PSA is a useful tool to avoid unnecessary prostatic biopsy in patients with a total PSA >10 μg/L.


1993 ◽  
Vol 150 (5 Part 2) ◽  
pp. 1740-1745 ◽  
Author(s):  
Takayoshi Demura ◽  
Yoshihiko Watarai ◽  
Masaki Togashi ◽  
Tetsuo Hirano ◽  
Nobuo Ohashi ◽  
...  

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