scholarly journals Human Tissue Kallikreins: A Family of New Cancer Biomarkers

2002 ◽  
Vol 48 (8) ◽  
pp. 1198-1205 ◽  
Author(s):  
Eleftherios P Diamandis ◽  
George M Yousef
Keyword(s):  
Prostate Cancer ◽  
Steroid Hormone ◽  
Specific Antigen ◽  
Serum Biomarkers ◽  
Protein Levels ◽  
The Past ◽  
Diagnosis And Prognosis ◽  
Glandular Kallikrein ◽  
Protease Enzyme ◽  
Enzymatic Pathways

Abstract Kallikreins are a subgroup of the serine protease enzyme family. Until recently, it was thought that the human kallikrein gene family contained only three members. In the past 3 years, the entire human kallikrein gene locus was discovered and found to contain 15 kallikrein genes. Kallikreins are expressed in many tissues, including steroid hormone-producing or hormone-dependent tissues such as the prostate, breast, ovary, and testis. Most, if not all, kallikreins are regulated by steroid hormones in cancer cell lines. There is strong but circumstantial evidence linking kallikreins and cancer. Prostate-specific antigen (PSA; hK3) and, more recently, human glandular kallikrein (hK2) are widely used tumor markers for prostate cancer. Three other kallikreins, hK6, hK10, and hK11, are emerging new serum biomarkers for ovarian and prostate cancer diagnosis and prognosis. Several other kallikreins are differentially expressed at both the mRNA and protein levels in various endocrine-related malignancies, and they have prognostic value. The coexpression of many kallikreins in the same tissues (healthy and malignant) points to the possible involvement of kallikreins in cascade enzymatic pathways. In addition to their diagnostic/prognostic potential, kallikreins may also emerge as attractive targets for therapeutics.

scholarly journals Prostate Cancer Liquid Biopsy Biomarkers’ Clinical Utility in Diagnosis and Prognosis

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3373
Author(s):  
Milena Matuszczak ◽  
Jack A. Schalken ◽  
Maciej Salagierski
Keyword(s):  
Prostate Cancer ◽  
Liquid Biopsy ◽  
Current Knowledge ◽  
Prostate Gland ◽  
Specific Antigen ◽  
Transrectal Ultrasound ◽  
Digital Rectal Examination ◽  
Cost Effective ◽  
Non Invasive ◽  
Diagnosis And Prognosis

Prostate cancer (PCa) is the most common cancer in men worldwide. The current gold standard for diagnosing PCa relies on a transrectal ultrasound-guided systematic core needle biopsy indicated after detection changes in a digital rectal examination (DRE) and elevated prostate-specific antigen (PSA) level in the blood serum. PSA is a marker produced by prostate cells, not just cancer cells. Therefore, an elevated PSA level may be associated with other symptoms such as benign prostatic hyperplasia or inflammation of the prostate gland. Due to this marker’s low specificity, a common problem is overdiagnosis, which leads to unnecessary biopsies and overtreatment. This is associated with various treatment complications (such as bleeding or infection) and generates unnecessary costs. Therefore, there is no doubt that the improvement of the current procedure by applying effective, sensitive and specific markers is an urgent need. Several non-invasive, cost-effective, high-accuracy liquid biopsy diagnostic biomarkers such as Progensa PCA3, MyProstateScore ExoDx, SelectMDx, PHI, 4K, Stockholm3 and ConfirmMDx have been developed in recent years. This article compares current knowledge about them and their potential application in clinical practice.

scholarly journals Proteomics in Diagnosis of Prostate Cancer/ Протеомика Во Дијагноза На Простатниот Карцином

PRILOZI ◽  
2015 ◽  
Vol 36 (1) ◽  
pp. 5-36 ◽  
Author(s):  
Katarina Davalieva ◽  
Momir Polenakovic
Keyword(s):  
Prostate Cancer ◽  
Tumor Tissue ◽  
Biomarker Discovery ◽  
Molecular Level ◽  
Specific Antigen ◽  
Shotgun Proteomics ◽  
Comparative Proteomics ◽  
Label Free ◽  
The Past ◽  
Proteomics Research

Abstract Prostate cancer (PCa) is the second most frequently diagnosed malignancy in men worldwide. The introduction of prostate specific antigen (PSA) has greatly increased the number of men diagnosed with PCa but at the same time, as a result of the low specificity, led to overdiagnosis, resulting to unnecessary biopsies and high medical cost treatments. The primary goal in PCa research today is to find a biomarker or biomarker set for clear and effecttive diagnosis of PCa as well as for distinction between aggressive and indolent cancers. Different proteomic technologies such as 2-D PAGE, 2-D DIGE, MALDI MS profiling, shotgun proteomics with label-based (ICAT, iTRAQ) and label-free (SWATH) quantification, MudPIT, CE-MS have been applied to the study of PCa in the past 15 years. Various biological samples, including tumor tissue, serum, plasma, urine, seminal plasma, prostatic secretions and prostatic-derived exosomes were analyzed with the aim of identifying diagnostic and prognostic biomarkers and developing a deeper understanding of the disease at the molecular level. This review is focused on the overall analysis of expression proteomics studies in the PCa field investigating all types of human samples in the search for diagnostics biomarkers. Emphasis is given on proteomics platforms used in biomarker discovery and characterization, explored sources for PCa biomarkers, proposed candidate biomarkers by comparative proteomics studies and the possible future clinical application of those candidate biomarkers in PCa screening and diagnosis. In addition, we review the specificity of the putative markers and existing challenges in the proteomics research of PCa.

Detection of COX-2 in liquid biopsy of patients with prostate cancer

2021 ◽  
pp. jclinpath-2021-207755
Author(s):  
Vanessa Silva Pereira ◽  
Beatriz da Costa Aguiar Alves ◽  
Jaques Waisberg ◽  
Fernando Fonseca ◽  
Flavia Gehrke
Keyword(s):  
Prostate Cancer ◽  
Slow Growth ◽  
Rna Extraction ◽  
Specific Antigen ◽  
Common Type ◽  
Control Group ◽  
Quantitative Real Time Pcr ◽  
Diagnosis And Prognosis ◽  
The Mean ◽  
Cox 2

AimsTo determine the profile of COX-2 gene expression in patients with prostate cancer attended at the ABC University Health Center outpatient clinic and correlate the results with patients’ anatomopathological examinations. Prostate cancer is the sixth most common type of cancer worldwide and the second in Brazil. COX-2 expression is associated with an unfavourable prognosis.Methods15.0 mL of peripheral blood were collected from 24 patients and 25 healthy men. RNA extraction was performed using the QIAamp RNA Blood Mini Kit. Complementary DNA synthesis was performed using SuperScript II RNAse Reverse Transcriptase. Quantitative real-time PCR was performed with specific COX-2 oligonucleotides and the endogenous GAPDH gene.ResultsThe mean age of the patients was 69 years old. The Gleason scoring system showed 37.5% of patients with Gleason 6 (slow growth, low risk), 45.8% with Gleason 7 (intermediate risk) and 16.7% with Gleason 8 or 9 (risk of high-grade cancer). The median COX-2 expression in the study group was 0.97, while in the control group it was 0.11 (p<0.045).ConclusionsPatients with prostate cancer showed higher COX-2 expression at diagnosis compared with the control group. Since COX-2 detection associated with prostate-specific antigen dosage shows promise as a biomarker for diagnosis and prognosis in patients with prostate cancer, further research is required to confirm these findings.

scholarly journals The Combination of Human Glandular Kallikrein and Free Prostate-specific Antigen (PSA) Enhances Discrimination Between Prostate Cancer and Benign Prostatic Hyperplasia in Patients with Moderately Increased Total PSA

1999 ◽  
Vol 45 (11) ◽  
pp. 1960-1966 ◽  
Author(s):  
Angeliki Magklara ◽  
Andreas Scorilas ◽  
William J Catalona ◽  
Eleftherios P Diamandis
Keyword(s):  
Prostate Cancer ◽  
Benign Prostatic Hyperplasia ◽  
Prostate Specific Antigen ◽  
Prostatic Carcinoma ◽  
Specific Antigen ◽  
Area Under The Curve ◽  
Prostatic Hyperplasia ◽  
Free Psa ◽  
Glandular Kallikrein ◽  
Total Psa

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.

scholarly journals Simultaneous Quantification of Prostate-specific Antigen and Human Glandular Kallikrein 2 mRNA in Blood Samples from Patients with Prostate Cancer and Benign Disease

2002 ◽  
Vol 48 (8) ◽  
pp. 1265-1271 ◽  
Author(s):  
Alice Ylikoski ◽  
Kim Pettersson ◽  
Jussi Nurmi ◽  
Kerttu Irjala ◽  
Matti Karp ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Benign Disease ◽  
Early Event ◽  
Blood Samples ◽  
Simultaneous Quantification ◽  
Glandular Kallikrein ◽  
External Calibration Curve ◽  
Kallikrein 2

Abstract Background: Detection or quantification of circulating cancer cells has been proposed as an aid in detection and monitoring of several solid tumors. We investigated the classification accuracy of prostate-specific antigen (PSA) and human glandular kallikrein 2 (hK2) mRNA copy numbers in blood for the differentiation of patients with prostate cancer (PC) and benign disease. Methods: PSA and hK2 mRNA expression was studied in blood samples from 51 men with PC and 19 men with benign disease. Among the PC patients, 10 had organ-confined disease (pT1–pT2). We used a multiplexed reverse transcription-PCR assay with two highly target-like mRNA internal standards for the simultaneous quantification of PSA and hK2 mRNA. An external calibration curve covered the range of 102–106 mRNA copies. Results: PSA and hK2 mRNA were detected in 41 of 51 (median, 1200 copies/0.5 mL of blood) and 43 of 51 (median, 3800 copies/0.5 mL of blood) patients with PC, respectively, whereas only 1 of 19 men with benign disease was positive for both mRNAs (1500 PSA and 3100 hK2 mRNA copies/0.5 mL of blood; P &lt;0.0001, Mann–Whitney U-test). Of the 10 patients with organ-confined PC, only 3 with low Gleason scores (≤5) were negative for both PSA and hK2 (P = 0.02, Mann–Whitney U-test). Conclusions: The presence of PC cells in the blood circulation is an early event in PC progression, and quantitative assays for PSA and hK2 mRNA discriminate benign from PC cases. Further studies are needed to determine the diagnostic accuracy and prognostic value of the assays.

Human glandular kallikrein as a tool to improve discrimination of poorly differentiated and non-organ-confined prostate cancer compared with prostate-specific antigen

Urology ◽  
2000 ◽  
Vol 55 (4) ◽  
pp. 481-485 ◽  
Author(s):  
Franz Recker ◽  
Maciej K Kwiatkowski ◽  
Timo Piironen ◽  
Kim Pettersson ◽  
Andreas Huber ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Glandular Kallikrein ◽  
Poorly Differentiated

Emerging Biomarkers for the Diagnosis and Prognosis of Prostate Cancer

2008 ◽  
Vol 54 (12) ◽  
pp. 1951-1960 ◽  
Author(s):  
Girish Sardana ◽  
Barry Dowell ◽  
Eleftherios P Diamandis
Keyword(s):  
Prostate Cancer ◽  
Early Diagnosis ◽  
Specific Antigen ◽  
Cost Effective ◽  
Detection Methods ◽  
Significant Advance ◽  
Specific Method ◽  
Diagnosis And Prognosis ◽  
Psa Testing ◽  
Formidable Challenge

Abstract Background: Early detection of prostate cancer (CaP), the most prevalent cancer and the second-leading cause of death in men, has proved difficult, and current detection methods are inadequate. Prostate-specific antigen (PSA) testing is a significant advance for early diagnosis of patients with CaP. Content: PSA is produced almost exclusively in the prostate, and abnormalities of this organ are frequently associated with increased serum concentrations. Because of PSA’s lack of specificity for CaP, however, many patients undergo unnecessary biopsies or treatments for benign or latent tumors, respectively. Thus, a more specific method of CaP detection is required to augment or replace screening with PSA. The focus recently has been on creating cost-effective assays for circulating protein biomarkers in the blood, but because of the heterogeneity of CaP, it has become clear that this effort will be a formidable challenge. Each marker will require proper validation to ensure clinical utility. Although much work has been done on variations of the PSA test (i.e., velocity, density, free vs bound, proisoforms) with limited usefulness, there are many emerging markers at various stages of development that show some promise for CaP diagnosis. These markers include kallikrein-related peptidase 2 (KLK2), early prostate cancer antigen (EPCA), PCA3, hepsin, prostate stem cell antigen, and α-methylacyl-CoA racemase (AMACR). We review biomarkers under investigation for the early diagnosis and management of prostate cancer. Summary: It is hoped that the use of panels of markers can improve CaP diagnosis and prognosis and help predict the therapeutic response in CaP patients.

scholarly journals Detection of Tear Biomarkers for Future Prostate Cancer Diagnosis

2010 ◽  
Vol 3 (1) ◽  
pp. 26-29 ◽  
Author(s):  
Yong Li
Keyword(s):  
Prostate Cancer ◽  
Benign Prostate Hyperplasia ◽  
Specific Antigen ◽  
Clinical Proteomics ◽  
Prostate Hyperplasia ◽  
Psa Test ◽  
Diagnosis And Prognosis ◽  
Novel Biomarkers ◽  
Unique Source ◽  
Benign Prostate

Prostate cancer (CaP) continues to be the second leading cause of cancer-specific death in men in Western countries. The marker currently used for CaP detection is an increase in serum prostate specific antigen (PSA). However, the PSA test may give false positive or negative information and does not allow the differentiation of benign prostate hyperplasia (BPH), non-aggressive CaP and aggressive CaP. Tears are a unique source of body fluid and contain proteins, peptides, mucins and lipids, which is useful for studying clinical proteomics. Advances in the field of proteomics have greatly enhanced the study of tears, with a greater number of proteins now being identified in tears. Identification of novel biomarkers in tear is a new area of development. Modern advances in the field of proteomic techniques hold the promise of providing the clinical oncologists with new tools to find novel CaP biomarkers for early diagnosis and prognosis.

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