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Current Opinion in Urology May 2017This article intends to review biomarkers derived from blood, urine, and tissue that can aid in the diagnosis of prostate cancer (PCa). (Review)
Review
PURPOSE OF REVIEW
This article intends to review biomarkers derived from blood, urine, and tissue that can aid in the diagnosis of prostate cancer (PCa).
RECENT FINDINGS
PCa screening requires tools that complement prostate-specific antigen (PSA) with a higher specificity for clinically significant disease. Novel blood biomarkers, such as the Prostate Health Index (phi) and 4Kscore, utilize isoforms of PSA to more accurately predict high-grade PCa than traditional tools such as PSA and the percentage free-to-total PSA. Several gene products associated with PCa can be detected in the urine through commercially available assays. PCa antigen 3 (PCA3), though approved for repeat biopsy decisions, appears inferior to other biomarkers such as phi for identifying aggressive disease. However, combinations of PCA3 with other urine assays have shown promising results. One tissue-based hypermethylation test, named ConfirmMDx, can also be used to determine the need for repeat biopsy in men with a prior negative biopsy.
SUMMARY
Several biomarkers have been developed to aid in the screening and diagnosis of PCa. Such tests are often indicated in men with moderately elevated PSA or history of a prior negative biopsy. Their use facilitates reduction of unnecessary biopsies without sacrificing the early diagnosis of clinically significant PCa.
Topics: Antigens, Neoplasm; Biomarkers, Tumor; Biopsy, Needle; Humans; Male; Predictive Value of Tests; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms
PubMed: 28212119
DOI: 10.1097/MOU.0000000000000384 -
Journal of Andrology 1995In vitro studies suggest that the protease activity of PSA might play a functional role to facilitate the growth and spreading of cancerous prostatic cells. hK2 may have... (Review)
Review
In vitro studies suggest that the protease activity of PSA might play a functional role to facilitate the growth and spreading of cancerous prostatic cells. hK2 may have similar properties. Further investigation to prove their in vivo effects is required. Regulation of PSA and hKLK2 gene expression is mediated not only by androgens, but also by a number of autocrine and paracrine factors, suggesting that the control mechanisms for expression of these genes are complex and multifaceted. Such factors may also be integral for the growth and differentiation of prostate cells. Thus PSA and hKLK2 may serve as useful markers to study the regulation of gene expression during cell growth and differentiation of the prostate.
Topics: Androgens; Gene Expression Regulation; Humans; Kallikreins; Prostate-Specific Antigen
PubMed: 7559150
DOI: No ID Found -
Biosensors & Bioelectronics Dec 2018Prostate specific antigen (PSA) is a widely used marker for the diagnosis of prostate cancer, and the increasing attention has been attracted on the development of rapid...
Prostate specific antigen (PSA) is a widely used marker for the diagnosis of prostate cancer, and the increasing attention has been attracted on the development of rapid assay using biosensing technology. However, it remains challenging for the sensitive and selective detection of PSA in clinical samples. Here, we report a label-free microfluidic paper-based analytical device for highly sensitive electrochemical detection of PSA. The paper device was fabricated with wax printing to generate hydrophobic and hydrophilic layers for the construction of microfluidic channel, followed by screen-printing of three electrodes including working, counter and reference electrode. Gold nanoparticles (AuNPs)/reduced graphene oxide (rGO)/thionine (THI) nano composites were synthesized and characterized, which were coated onto working electrodes for the immobilization of DNA aptamer probe. THI servers as the electrochemical mediator to transduce the biological recognition between DNA aptamer and PSA, and the excellent conductivity of AuNPs and rGO also play a significant role of electron transfer, leading to a sensitive detection for PSA, able to detect PSA as low as 10 pg mL, with a linear range from 0.05 to 200 ng mL. We demonstrated that our electrochemical sensor for the detection of clinical serum samples, indicating that our sensor would provide a new platform for low cost, sensitive and point-of-care diagnosis of prostate cancer.
Topics: Aptamers, Nucleotide; Blood Chemical Analysis; Electrochemical Techniques; Electrodes; Gold; Graphite; Humans; Limit of Detection; Male; Metal Nanoparticles; Nanocomposites; Prostate-Specific Antigen
PubMed: 30196046
DOI: 10.1016/j.bios.2018.08.067 -
Medical Principles and Practice :... 2019To describe the reference ranges of serum prostate-specific antigen (PSA) in Saudi men. Materials/Subjects and Methods: Saudi males, aged 30 and above, were invited to...
OBJECTIVE
To describe the reference ranges of serum prostate-specific antigen (PSA) in Saudi men. Materials/Subjects and Methods: Saudi males, aged 30 and above, were invited to participate in the study. Blood samples were taken from each subject to determine serum levels of PSA. Blood sugar levels, lipid profile, and anthropometric measurements were also obtained.
RESULTS
Our cohort consisted of 7,814 men; their mean PSA level was 1.24 ng/mL. The majority (90.5%) had PSA values between 0 and 2.5 ng/mL. The median PSA and the 95th percentile increased steadily with age. There was a sharp increase in the 95th percentile, from 3.8 ng/mL in men between 60 and 70 years old to 6.9 ng/mL in men over 71 years old. The 95th percentiles of PSA serum levels were lower in Saudi men than in the general population.
CONCLUSIONS
PSA serum levels in Saudi men are lower than in other communities. Creating age-specific reference ranges could improve the sensitivity of the PSA tests by allowing the detection of treatable tumors in younger men if the threshold of 4.0 ng/mL is lowered. Furthermore, unnecessary biopsies among older men may be avoided if the threshold is increased.
Topics: Adult; Age Factors; Aged; Arabs; Body Weights and Measures; Cross-Sectional Studies; Humans; Lipids; Male; Middle Aged; Prostate-Specific Antigen; Reference Values; Saudi Arabia
PubMed: 30731465
DOI: 10.1159/000497744 -
Journal of Clinical Laboratory Analysis 2011Prostate-specific antigen (PSA) is the most important biochemical tumor marker for the early detection of prostate cancer; however, its diagnostic specificity is low.... (Comparative Study)
Comparative Study
OBJECTIVE
Prostate-specific antigen (PSA) is the most important biochemical tumor marker for the early detection of prostate cancer; however, its diagnostic specificity is low. Therefore, free PSA (fPSA) test is recommended as an adjunct to increase the specificity. However, all the current technology only allows detecting one biomarker at one time. In this study, we reported a flexible bead-based immunoassay to measure total PSA (tPSA) and fPSA simultaneously.
MATERIALS AND METHODS
We used the Luminex xMAP bead array technology to measure tPSA and fPSA at one time, employing two mouse monoclonal anti-PSA antibodies (5G6 and 8A6) for coating and another mouse monoclonal anti-PSA antibody (5A6) for detection. Then we compared the data of Luminex assay with that of the conventional enzyme-linked immunosorbent assay (ELISA).
RESULTS
The assay was fast with a wide dynamic range. The lower detection limit for tPSA and fPSA were 2.3 and 1.3 pg/ml. The inter-assay coefficients for tPSA and fPSA were between 5.64 and 7.65%, and the intra-assay coefficients for tPSA and fPSA were between 4.15 and 5.89%. A close correlation between the new assay and the conventional ELISA was observed.
CONCLUSIONS
The bead-based platform is rapid, sensitive, and less expensive, which allows both single sample and high-throughput measurement of tPSA and fPSA over a wide range of concentrations.
Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Early Detection of Cancer; Fluoroimmunoassay; Humans; Limit of Detection; Male; Microspheres; Prostate-Specific Antigen; Prostatic Neoplasms; Reproducibility of Results; Sensitivity and Specificity
PubMed: 21254241
DOI: 10.1002/jcla.20427 -
The Journal of Urology Oct 1997The free uncomplexed form of prostate specific antigen (f-PSA) from prostate cancer sera was partially isolated and characterized because the molecular form of f-PSA in...
PURPOSE
The free uncomplexed form of prostate specific antigen (f-PSA) from prostate cancer sera was partially isolated and characterized because the molecular form of f-PSA in the serum is unknown.
MATERIALS AND METHODS
230 ml. of sera from 59 men with bone metastasis and individual PSA values of >2000 ng./mL were combined and centrifuged for 60 minutes at 30,000 RPM (4C). The sera were fractionated by gel filtration column chromatography (Sephacryl S-200, 2.5 cm. x 92 cm.). Free and complexed PSA in the eluted fractions were isolated by measuring immunoreactivity of PSA (Tosoh AIA-600 assay); f-PSA from 23 separate runs were combined, concentrated and re-chromatographed. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used to immobilize the isolated proteins onto a nitrocellulose membrane and a polyvinylidene difluoride (PVDF) membrane. Monoclonal antibody (F5) was used to probe PSA on nitrocellulose membrane and the PSA band was detected by Emission Chemoluminescence (ECL) kit. Amino terminal sequence analysis of the isolated f-PSA was performed with a gas-phase sequentor (Applied Biosyntens 4760 A) using the program designed by the manufacturer.
RESULTS
0.5 cc of f-PSA (27,000 ng./mL) was obtained from serums after rechromatography. SDS-PAGE showed one double band around 30 kDa; with ECL technique, one major band at 30-kDa was identified as PSA. The amino terminal sequence analysis of this band showed residue 1 through 9 and 146 through 152.
CONCLUSIONS
In our preliminary experiment, the free form of serum PSA is partially isolated directly from human sera. Amino terminal sequence analysis has shown that serum f-PSA is not a pre-mature or zymogen form of PSA because serum f-PSA has a N-terminus identical to that of seminal fluid PSA. A nicked form of f-PSA is also found in these patient sera.
Topics: Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms
PubMed: 9302183
DOI: No ID Found -
Journal of Cancer Research and... 2017Serum prostate-specific antigen (PSA) is a useful tumor biomarker for prostate cancer (PCa) diagnosis. In this study, I aimed to compare the free/total PSA (fPSA%) with...
Diagnostic efficacy of free prostate-specific antigen/total prostate-specific antigen ratio for the diagnosis of prostate cancer in low concentration (≤4 ng/ml) and intermediate levels of total prostate-specific antigen (4.01-10.0 ng/ml).
AIM OF STUDY
Serum prostate-specific antigen (PSA) is a useful tumor biomarker for prostate cancer (PCa) diagnosis. In this study, I aimed to compare the free/total PSA (fPSA%) with PSA alone for their usefulness in diagnosis for PCa.
METHODS
The patients who underwent prostate biopsy between January 2010 and January 2015 were evaluated retrospectively. Data were expressed as a mean + standard error and P < 0.05 as considered with statistical significance (Med Calc 14.12-2014). The receiver operating characteristic curves were calculated to study the sensitivity and specificity of fPSA and PSA and compared to each other in different PSA levels.
RESULTS
There were 1055 patients in the study. The mean age of the patients was 64.2 + 7.5 and 66.3 + 6.4 years in Groups 1 and 2. The mean PSA and free/total PSA of the patients was 2.79 + 1 ng/ml, 0.2 + 0.08 and 6.49 + 1.59 ng/ml and 0.19 + 0.09 in Groups 1 and 2, respectively. I found the optimal cutoff for fPSA% was ≤18 and ≤14 in Groups 1 and 2 with a sensitivity of 62-45% and specificity of 58-79%. There was a statistical significant difference for fPSA when comparing the area under curve in the PSA level of 4.01-10 ng/ml (P = 0.0009).
CONCLUSION
In this study, serum fPSA% has advantages for diagnosis of PCa when comparing PSA alone in different levels of PSA. These advantages are significant in PSA level of 4.01-10 ng/ml.
Topics: Aged; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Sensitivity and Specificity
PubMed: 28643748
DOI: 10.4103/0973-1482.183177 -
Journal of Clinical Laboratory Analysis 1999We have analyzed matched serum and breast cyst fluid samples for total PSA from 148 patients with fibrocystic breast disease. We have also determined the molecular forms...
We have analyzed matched serum and breast cyst fluid samples for total PSA from 148 patients with fibrocystic breast disease. We have also determined the molecular forms of PSA (free PSA and PSA bound to alpha1-antichymotrypsin) in 78 breast cyst fluid samples. We found that total PSA can be detected in all cyst fluids and in about 75% of female sera. The median total PSA concentration in breast cyst fluid (bcf) is about 30 times higher than the median in the corresponding sera. Breast cyst fluid and serum PSA are not correlated with each other. Total serum PSA is inversely associated with patient age but the inverse association between bcf PSA and age is weak. Lower total PSA in bcf was seen in women who breast feed, and higher bcf PSA is associated with multiple cysts. Type I cysts (with a high K+/ Na+ ratio) tend to have higher total PSA than Type II cysts. All but three of the fractionated cyst fluids (75/78; 96%) had free PSA as the predominant molecular form. The most consistent finding of our study was the positive association between the cyst fluid K+/Na+ ratio and the free to bound PSA ratio. This association was confirmed by Spearman correlation as well as by Wilcoxon and chi-square analysis. Secretory/apocrine cysts (Type I) tend to have more total PSA and proportionally more free PSA than transudative/flattened cysts (Type II).
Topics: Adult; Aged; Aging; Breast Feeding; Cyst Fluid; Female; Fibrocystic Breast Disease; Humans; Middle Aged; Postmenopause; Potassium; Prostate-Specific Antigen; Sodium; alpha 1-Antichymotrypsin
PubMed: 10102136
DOI: 10.1002/(SICI)1098-2825(1999)13:2<75::AID-JCLA6>3.0.CO;2-F -
British Journal of Cancer Mar 2022Altered prostate-specific antigen (PSA) glycosylation patterns can be useful biomarkers in detecting high-grade prostate cancer (HGPC). The microfluidic immunoassay...
BACKGROUND
Altered prostate-specific antigen (PSA) glycosylation patterns can be useful biomarkers in detecting high-grade prostate cancer (HGPC). The microfluidic immunoassay system can analyse α2,3-linked sialylated PSA (α2,3-Sia-PSA) and α1,6-linked fucosylated PSA (α1,6-Fuc-PSA) using different lectins, Mackkia amurensis agglutinin and Pholiota squarrosa lectin, respectively. Here, we investigated the diagnostic value of simultaneous analysis of α2,3-Sia-PSA and α1,6-Fuc-PSA for the detection of HGPC.
METHODS
Men with serum PSA levels of 4-20 ng/mL who underwent prostate biopsy were included. The model to predict HGPC (Gleason grade ≥2) was constructed by multivariate logistic regression analysis, in combination with α2,3-Sia-PSA and α1,6-Fuc-PSA (SF index).
RESULTS
In the development cohort (n = 150), the SF index showed good discrimination for HGPC (area under the receiver-operating curve (AUC) 0.842; 95% confidence interval (CI) 0.782-0.903), compared to the single PSA test (AUC 0.632, 95% CI 0.543-0.721), α2,3-Sia-PSA (AUC 0.711, 95% CI 0.629-0.793) and α1,6-Fuc-PSA (AUC 0.738, 95% CI 0.657-0.819). Decision-curve analysis showed the superior benefit of the SF index. In the validation cohort (n = 57), the SF index showed good discrimination for HGPC (AUC 0.769, 95% CI 0.643-0.895).
CONCLUSIONS
The SF index could differentiate HGPC, providing useful information for decision making for prostate biopsy in men with abnormal PSA levels.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Glycosylation; Humans; Logistic Models; Male; Microfluidic Analytical Techniques; Middle Aged; Neoplasm Grading; Prostate-Specific Antigen; Prostatic Neoplasms; Sensitivity and Specificity
PubMed: 34802050
DOI: 10.1038/s41416-021-01637-x -
Medical Science Monitor : International... Aug 2019BACKGROUND Although magnetic resonance imaging (MRI)-targeted biopsy and saturation biopsy can improve the accuracy of prostate biopsy, transrectal ultrasound...
BACKGROUND Although magnetic resonance imaging (MRI)-targeted biopsy and saturation biopsy can improve the accuracy of prostate biopsy, transrectal ultrasound (TRUS)-guided prostate biopsy is still the cornerstone for diagnosis of prostate cancer. However, it is not clear whether it is necessary to perform the same TRUS-guided biopsy scheme for patients with different prostate specific antigen (PSA) or prostate specific antigen density (PSAD) levels. The purpose of this study was to evaluate the optimal core number for specific suspected prostate cancer patients. MATERIAL AND METHODS There were 398 patients who underwent 12-core biopsy scheme, who were included in this retrospective analysis. The 12-core scheme incorporated a classic sextant scheme and 4-core biopsies from the base and middle regions bilaterally. The cancer detection rates of patients with different PSA or PSAD levels between the 12-core, sextant, 4-core, and 2-core biopsy were compared. RESULTS The differences in cancer detection rates between the 12-core biopsy scheme and the sextant biopsy scheme were significant in patients with PSA <20 ng/mL or PSAD <0.3. There were no differences in the cancer detection rates between the 12-core biopsy scheme and the 4-core biopsy scheme in patients with PSA ≤50 ng/mL or PSAD ≤1.0. There were significant differences between 12-core and 2-core scheme when PSA ≤70 ng/mL or PSAD ≤1.5. CONCLUSIONS We recommend that the 12-core biopsy should be used for patients with PSA <20 ng/mL or PSAD <0.3. The biopsy scheme in patients with PSA 20-50 ng/mL or PSAD 0.3-1.0 should be considered in combination with DRE and MRI. For patients with PSA >50 ng/mL or PSAD >1.0, we recommend 6-core or 4-core biopsy by comprehensively considering multiple factors. The 2-core biopsy is recommended for patients with PSA >70 ng/mL or PSAD >1.5.
Topics: Aged; Aged, 80 and over; Biopsy; Biopsy, Large-Core Needle; China; Humans; Kallikreins; Male; Microscopy, Acoustic; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies; Ultrasonography
PubMed: 31424055
DOI: 10.12659/MSM.915826