scholarly journals Early prediction of prostate cancer biochemical recurrence and identification of disease persistence using PSA isoforms and human kallikrein-2

Tumor Biology ◽  
2021 ◽  
Vol 43 (1) ◽  
pp. 197-207
Author(s):  
Joana Do Carmo Silva ◽  
Stepan Vesely ◽  
Hana Luksanova ◽  
Richard Prusa ◽  
Marko Babjuk
Keyword(s):  
Prostate Cancer ◽  
Biochemical Recurrence ◽  
Specific Antigen ◽  
Early Postoperative Period ◽  
P Value ◽  
Single Marker ◽  
Human Kallikrein 2 ◽  
Kallikrein 2 ◽  
Disease Persistence

BACKGROUND: The role of isoforms of prostate specific antigen (PSA) and other kallikrein-related markers in early detection of biochemical recurrence (BCR) after radical prostatectomy (RP) is not well known and serum PSA is currently used in preoperative risk nomograms. OBJECTIVE: The aim of this research was to study pre- and early postoperative levels of important PSA isoforms and human kallikrein-2 to determine their ability to predict BCR and identify disease persistence (DP). METHODS: This study included 128 consecutive patients who underwent RP for clinically localized prostate cancer. PSA, fPSA, %fPSA, [–2]proPSA, PHI and hK2 were measured preoperatively, at 1 and 3 months after RP. We determined the ability of these markers to predict BCR and identify DP. RESULTS: The DP and BCR rate were 11.7%and 20.3%respectively and the median follow up was 64 months (range 3–76 months). Preoperatively, the independent predictors of BCR were PSA (p-value 0.029), [–2]proPSA (p-value 0.002) and PHI (p-value 0.0003). Post-RP, PSA was the single marker correlating with BCR, both at one (p-value 0.0047) and 3 months (p-value 0.0004). PSA, fPSA, [–2]proPSA and PHI significantly correlated to DP at 1 and 3 months post-RP (p-value <  0.05), although PSA had the most significant existing correlation (p-value <  0.0001). CONCLUSIONS: [–2]proPSA and PHI are preoperative predictors of BCR and DP that outperform the currently used serum PSA. At the early postoperative period there is no additional benefit of the other markers tested.

scholarly journals Development of Sensitive Immunoassays for Free and Total Human Glandular Kallikrein 2

2004 ◽  
Vol 50 (9) ◽  
pp. 1607-1617 ◽  
Author(s):  
Ville Väisänen ◽  
Susann Eriksson ◽  
Kaisa K Ivaska ◽  
Hans Lilja ◽  
Martti Nurmi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Detection Limit ◽  
Solid Phase ◽  
Specific Antigen ◽  
Control Group ◽  
Serum Samples ◽  
Human Kallikrein 2 ◽  
Kallikrein 2 ◽  
Capture Antibody ◽  
Total Psa

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.

The value of (−7, −5)pro-prostate-specific antigen and human kallikrein-2 as serum markers for grading prostate cancer

2004 ◽  
Vol 93 (6) ◽  
pp. 720-724 ◽  
Author(s):  
C.H. Bangma ◽  
M.F. Wildhagen ◽  
G. Yurdakul ◽  
F.H. Schröder ◽  
B.G. Blijenberg
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Serum Markers ◽  
Human Kallikrein 2 ◽  
Kallikrein 2

Single Nucleotide Polymorphism of the Human Kallikrein-2 Gene Highly Correlates With Serum Human Kallikrein-2 Levels and in Combination Enhances Prostate Cancer Detection

2003 ◽  
Vol 21 (12) ◽  
pp. 2312-2319 ◽  
Author(s):  
Robert K. Nam ◽  
William W. Zhang ◽  
John Trachtenberg ◽  
Eleftherios Diamandis ◽  
Ants Toi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Odds Ratio ◽  
Adjusted Odds Ratio ◽  
Specific Antigen ◽  
Prostate Cancer Risk ◽  
Wild Type ◽  
Patients With Cancer ◽  
Prostate Biopsies ◽  
Human Kallikrein 2 ◽  
Kallikrein 2

Purpose: We examined the relationship between a mutant (T) for wild-type (C) allele substitution of the human kallikrein-2 gene (KLK2), circulating human kallikrein-2 (hK2) levels and prostate cancer risk.Patients and Methods: We studied 1,287 consecutive men who underwent prostate biopsies because of an abnormal prostate-specific antigen level. Serum and DNA were obtained before biopsy. Cases were patients with cancer, and controls were patients with no cancer. The mutant and wild-type alleles of the KLK2 gene were designated as the T and C alleles, respectively.Results: Of the 1,287 men, 616 had cancer, and 671 had no cancer. The overall distribution of the CC, CT, and TT KLK2 genotypes was 55.1%, 38.2%, and 6.8%, respectively. The median hK2 levels for men with the CC, CT, and TT genotypes were 0.24, 0.18, and 0.062 ng/mL and correlated with the genotypes, respectively (P = .0001). The adjusted odds ratios for prostate cancer for patients with the TT and CT genotypes compared with patients with the CC genotype, were 2.13 (95% confidence interval [CI], 1.3 to 3.5; P = .004) and 1.51 (95% CI, 1.2 to 2.0; P = .002), respectively. The adjusted odds ratio for prostate cancer for patients in the fourth quartile of hK2 compared with the first quartile was 4.33 (95% CI, 2.9 to 6.4; P = .0001). When combined, the adjusted odds ratio for having prostate cancer was 13.92 (95% CI, 6.6 to 29.2; P = .0001) for patients with high hK2 levels and at least one T allele.Conclusion: The C/T polymorphism of the KLK2 gene and circulating levels of hK2 are correlated and, in combination, are highly predictive for prostate cancer.

Circulating tumor cells (CTCs) in biochemical recurrence (BR) of prostate cancer: Final results.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 179-179 ◽  
Author(s):  
Jeanny B. Aragon-Ching ◽  
Samuel J. Simmens ◽  
Ramez Andrawis ◽  
Frederick Hendricks ◽  
Harold Frazier ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Biochemical Recurrence ◽  
Metastatic Prostate Cancer ◽  
Specific Antigen ◽  
Primary Treatment ◽  
Test Results ◽  
Undetectable Level ◽  
Bony Lesions ◽  
Prognostic Implications

179 Background: CTCs have known prognostic implications in metastatic prostate cancer. We presented initial data on the role of CTCs in BR of prostate cancer (Aragon-Ching et. al., ASCO GU 2011). The primary aim of this study was to determine whether there is a correlation between the number of CTCs with prostate specific antigen (PSA) levels and PSA doubling time (PSADT) in men with BR. Methods: BR was defined as patients who have undergone primary treatment with prostatectomy or radiation or both, with a rise to ≥ 0.2 from a prior undetectable level for prior prostatectomy or > 2 mg/dl rise for post-nadir radiotherapy. 36 patients (pts) were enrolled from May 2010 to May 2012. CTCs were evaluated in 7.5 mL of peripheral blood using the CTC CellSearch test. Results: The median age for 36 pts was 69.5 (range: 51 – 91) with a median PSA of 1.65 ng/mL (range 0.2 – 65.8) and testosterone levels of 315 ng/dL (range: 31 – 727). Gleason scores ranged from 5 to 9 (median=7). Prostatectomy was the primary treatment in 25 pts, radiotherapy in 9 pts, Cyberknife in 1 pt and combined radiohormones in 1 pt. PSADT varied between 0.35 to 55 months, with a median of 7.43 mos. The incidence of positive CTCs was 8.3% (3 out of 36 pts) of whom 2 had biopsy-proven bony lesions upon presenting with equivocal scans. The 3 pts who had measurable CTCs had PSADT of 2.27, 4.99 and 3.08 months, respectively. Conclusions: Obtaining CTCs in unselected patients presenting with biochemical recurrence have low yield. However, obtaining a positive CTC raises the suspicion of presence of metastatic disease and may have utility for longitudinal follow-ups of patients with BR. Supported by IRG-08-091-01 from ACS to GWU Cancer Institute.

What is the role of microRNA-301A expression as a diagnostic and predictive marker of biochemical recurrence for prostate cancer?

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 19-19
Author(s):  
Adnan Dervishi ◽  
Samarpit Rai ◽  
Kristy Doan Nguyen ◽  
Thomas Michael FitzGibbon ◽  
Paul Knoll ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Biochemical Recurrence ◽  
Clinical Decision Making ◽  
Specific Antigen ◽  
Predictive Marker ◽  
Clinical Decision ◽  
Definitive Treatment ◽  
Serum Samples ◽  
Prostate Hyperplasia

19 Background: Prostate specific antigen (PSA) screening for prostate cancer (PCa) remains controversial, due to its association with an increase in overdiagnosis of clinically insignificant PCa, and overtreatment. Hence, the need for more specific biomarkers to detect PCa and determine its prognosis. MicroRNA expression has previously been demonstrated as a biomarker to detect several malignancies. Studies suggest that microRNA-301a (miR-301a) inhibits the pro-apoptotic function of RUNX3, a transcription factor, and consequently activates ROCK1-mediated survival signaling in PCa. This study establishes the role of miR-301a as a reliable biomarker that can distinguish between patients with benign prostate hyperplasia (BPH) and PCa, and predict biochemical recurrence (BCR) after definitive treatment of PCa. Methods: Serum samples and tissue from prostate biopsies were collected from patients with an elevated PSA prospectively. The expression of miR- 301a was measured via reverse transcriptase-polymerase chain reaction. Additionally, miR-301a expression was retrospectively evaluated in prostatic tissue of 50 patients with PCa, including benign tissue, and correlated with clinico-pathological characteristics to predict BCR. Immunohistochemistry was performed to confirm the molecular target of miR-301a in cancerous tissue. Results: miR-301a demonstrated a significantly higher expression (p = 0.013) in both PCa tissue (Gleason 6 & 7 PCa) and serum samples (p = 0.011) when compared to BPH. Expression of miR-301a in Gleason 6 & 7 prostatectomy specimens positively correlated with patients who developed BCR when compared to patients who did not. When compared to the current nomogram for the prediction of PCa (i.e., PSA, age, race, Gleason score, and family history), incorporation of miR-301a was associated with a superior prediction of BCR at three years post-prostatectomy. Conclusions: miR-301a expression is a valuable tool for diagnosing PCa in patients with an elevated PSA. Combining miR-301a with PSA is associated with better risk stratification of PCa patients, and may help facilitate clinical decision making.

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