Tumor Marker For Prostate Cancer Research Articles

A Comparison Study on the Metabolites in PC-3, RWPE-1, and Chrysin-Treated PC-3 Cells

Prostate cancer is frequently diagnosed and the leading cause of death in men worldwide. Prostate-specific antigen (PSA) blood tests and biopsies are the primary methods for diagnosing prostate cancer; however, their accuracy is less than 50%. Therefore, there is a need to develop diagnostic tests that minimize patient discomfort during examination and adequate biomarkers that are more accurate, sensitive, and specific for the detection of prostate cancer. This study investigated the application of metabolomics to identify biomarkers in prostate cancer biofluids. In addition, changes in prostate cancer metabolite levels induced by chrysin, a natural anticancer compound, were evaluated and compared with those in non-treated prostate cancer cells. Gas chromatography-mass spectrometry (GC-MS)-based metabolomic profiling was performed to investigate the differences in metabolic alterations among prostate cancer, normal prostate, and chrysin-treated prostate cancer cells. Pairwise comparisons of the extracellular fluid metabolomes were performed using principal component analysis (PCA), partial least squares–discriminant analysis (PLS-DA), and Student’s t-test. The results revealed significantly different patterns among the metabolite groups, including alcohols, amino acids, carboxylic acids, organic acids, sugars, and urea. The RWPE-1- and chrysin-treated PC-3 (PC-3 Chr) cell groups showed similar tendencies for 23 metabolites, while the groups showed significant differences from the PC-3 group. Most amino acids showed higher concentrations in PC-3 cells than in the normal cell line RWPE-1 cells and PC-3 Chr cells. Our results revealed that GC-MS might be an effective diagnostic tool to detect prostate cancer and contribute to finding new tumor markers for prostate cancer as the basis for new ideas.

B-376 Performance of Pathological Anatomy Immunohistochemical Markers and Serum Tumor Markers in Prostate Cancer

Abstract Background The gold standard method for diagnosing prostate cancer is systematic prostate biopsy under ultrasound guidance and local anesthesia.Serum tumor marker tests (PSA, Free PSA and testosterone) and confirmatory or classificatory immunohistochemical (IHC) complement the conclusion of the patient’s report. The maximum amount of information regarding the pathological anatomy and markers provided to physicians favors assertive decision-making in the conduct of treatment. However, the results of prostate biopsies after treatment with prostatectomy can differ significantly in the course of the disease. In this context, the authors’ objectives were to analyze the performance of the dosages of these widely used serum markers against the IHC markers of biopsies, as well as their indicators of positive and negative predictive values (PPV and NPV) for prostatic neoplasms. The authors analyzed the level of agreement between pathological prostate biopsy results and immunohistochemical (IHC) testing for 34ßE12, p63, and alpha-methylacyl-CoA racemase (AMACR) to provide final pathological results for prostate cancer, as well as their relationship with data provided by biochemical tests for the markers PSA, Free PSA and Testosterone. Methods Descriptive, retrospective study with a qualitative and quantitative approach, based on data obtained through IHC exams and available in a database of a large laboratory in São Paulo—Brazil. Data collection was based on anatomopathological results of male patients diagnosed with prostate cancer, aged between 40 and 69 years between August 2021 and December 2022 with a total of 1403 analyzes for biopsies using IHC combined markers such as 34ßE12 , p63 and AMACR, and a total of 144 analyzes for combined prostatic serum markers (total PSA, free PSA and testosterone). All analyzes were conducted using the R software version 4.1.0 (R CORE TEAM, 2021) and considered a significance level (α) of 5%. Results The Mann-Whitney test indicated that the distribution of the PSA variable (ng/dL) does not differ statistically between the 34ßE12 groups (W = 822.0; P = 0.224; r = 0.139 , p63 (W = 826.0; P = 0.361 ; r = 0.103), and AMACR (W = 610.0; P = 0.351; r = -0.106). Likewise, the Free PSA marker (ng/dL) did not differ statistically between 34ßE12 (W = 309.5; P = 0.473 ; r = -0.097), p63 (W = 319.5; P = 0.488; r = - 0.093 and AMACR (W = 372.0; P = 0.725; r = 0.048). The results of the ROC curve with PSA (ng/dL) as predictor of the biopsy result with the marker 34ßE12, p63 and AMACR the mean positive predictive values (MPVP) were 0.623 , 0.635 and 0.615 respectively. For Free PSA (ng/dL) with the markers respectively, the VPPM were 0.743, 0.750 and 0.455. As for testosterone, our sample was very small. Conclusion Our findings showed that all markers are important indicators for the diagnosis and monitoring of prostate cancer and that they complement each other. Free PSA showed good PPV for 34ßE12 and p63 markers and low PPV for AMACR.

The Role of Free Prostate-Specific Antigen in the Diagnosis of Prostate Carcinoma: A Cross-Sectional Study in Rajshahi, Bangladesh

The prevalence of prostatic carcinoma is the outcome of several factors including improved awareness the general population of the significance of carcinoma of the prostate and progresses in diagnostic approaches. The PSA is a probable prostate cancer tumor marker, although it cannot distinguish prostate cancer from BPH solely. To assess the usefulness of free, total, and free/total PSA ratios in differentiating BPH and prostate cancer has been studied under this research work. The work was carried out at RMCH during April 2021 to March 2022, 350 purposively selected urology outpatients and inpatients at RMCH were studied cross-sectional study. Trans-rectal ultrasound (TRUS) and serum PSA levels were analyzed along with Digital rectal examination (DRE). A digital guided prostatic biopsy using a monopty biopsy gun confirmed the diagnosis. Data analysis was done in SPSS 26 software program. Prostatic cancer was more prevalent in men aged 70-80, whereas BPH was more common in men aged 60-70 (p = 0.00032). Histopathology revealed 95 prostate cancer patients, 82 with PSA >4 ng/ml and 85 patients had f/t PSA ratio>0.16. BPH was found in 255 individuals. 139 BPH patients had total PSA >4 ng/ml and 245 BPH patients had f/t PSA ratio ≤0.16. Total PSA had sensitivity and specificity of 86.32% and 45.49%, respectively, lower than f/t ratio. The (Positive predictive value) PPV and accuracy was significantly higher in f/t ratio than total PSA. Along with total PSA, free and free/total PSA ratio may help detect prostate cancer early and distinguish BPH from prostate cancer. J Bio-Sci. 30(1): 79-89, 2022 (June)

Construction of a sensitive and selective plasmonic biosensor for prostate specific antigen by combining magnetic molecularly-imprinted polymer and surface-enhanced Raman spectroscopy

Selective and sensitive detection of cancer biomarkers in serum samples is critical for early diagnosis of cancer. Prostate specific antigen is an important biomarker of prostate cancer, which ranks high among cancer-related deaths of men over 50 years old. Herein, a novel analytical method was introduced for detection of PSA by combining high selectivity of molecularly-imprinted polymers and high sensitivity of surface-enhanced Raman spectroscopy (SERS). Firstly, magnetic nanoparticles were grafted with an imprinted layer by using tannic acid as a functional monomer, diethylenetriamine as a cross-linker and prostate specific antigen as a template molecule. Detailed surface characterization and re-binding experiment results indicated that the imprinting of the antigen was successful with an imprinting factor of 5.58. The prepared magnetic molecularly imprinted polymers (MMIPs) were used as an antibody-free capture probe and labeled with gold nanoparticles that were modified with anti-PSA and a Raman reporter, namely 5,5′-dithiobis-(2-nitrobenzoic acid). Thus, a plasmonic structure (sandwich complex) was formed between MMIP and the SERS label. The limit of detection and limit of quantification of the designed sensor were 0.9 pg/mL and 3.2 pg/mL, respectively. The sensor also showed high recovery rates (98.0–100.1% for healthy person and 99.0–101.3% for patient) with low standard deviations (less than 4.3% for healthy person and less than 3.3% for patient) for PSA in serum samples. Compared with the traditional immunoassays, the proposed method has several advantages like low cost, reduced detection procedure, fast response, high sensitivity and selectivity. It is believed that the proposed method can be potentially used for selective and sensitive determination of tumor marker of prostate cancer in clinical applications.

Prostate Cancer-Induced Changes in Urinary Odors at Biomarker Concentrations of PPQ with Validation by Sniffer Mouse Behavioural Assays

Although prostate-specific antigen (PSA) is a significant tumor marker for prostate cancer at present, the low specificity (approximately 33%) and so on likely lead to an overdiagnosis and patient suffering from highly invasive prostate biopsy. Complementary measures with cancer-characteristic biomarkers could improve the specificity and accuracy of diagnosis before the biopsy. Previously, “sniffer mice” were shown to be super-sensitive to differences in odors and to discriminate between odors of urine mixtures from patients with bladder cancer before and after tumor resection as well as urine odors of mice with or without experimental tumors. Here, we showed that the sniffer mice discriminate efficiently urinary odors of patients with prostate cancer using an odor plume-guided Y-maze behavioural assay. Through discrimination training in forced-odor choice, statistically significant increases in correct odor choice rates showed the super-sensitivity of sniffer mice to the olfactory cue of ppq-level urinary biomarkers for prostate cancer in 106 -fold diluted urine samples, where donor-unique odors were below the threshold. Moreover, we validated eight volatile urinary biomarkers nearly at their original relative concentrations as the prostate cancer cue even when adding a similar biomarker profile to the post-radical prostatectomy urine samples by the same behavioural score of the sniffer mice. These biomarkers and profiles could be useful for non-invasive tests for prostate and bladder cancers.

Prostate-Specific Antigen Within the Reference Range, Subclinical Coronary Atherosclerosis, and Cardiovascular Mortality.

Although PSA (prostate-specific antigen)-a tumor marker for prostate cancer-has been reported to be associated with cardiovascular disease (CVD) risk factors, studies on the association of PSA with subclinical and clinical CVD remain limited. We examined the association of total serum PSA within the reference range with coronary artery calcium (CAC) score and CVD mortality. A cross-sectional study was performed in 88 203 Korean men who underwent a health checkup exam including cardiac tomography estimation of CAC score. Logistic regression model was used to calculate odds ratios with 95% CIs for prevalent CAC. PSA levels were inversely associated with the presence of CAC. After adjusting for potential confounders, multivariable-adjusted odds ratio (95% CIs) for prevalent CAC comparing PSA quartiles 2, 3, and 4 to the first quartile were 0.96 (0.90-1.01), 0.88 (0.83-0.93), and 0.85 (0.80-0.90), respectively ( P for trend, <0.001). A cohort study was performed in 243 435 Korean men with a mean age of 39.3 years, PSA values of <4.0 ng/mL, and without known CVD or prostate disease who were followed up with for ≤14 years for CVD mortality (median, 7.3 years). CVD deaths were ascertained through linkage to national death records. Hazard ratios and 95% CIs for CVD mortality were estimated using Cox proportional hazards regression analyses. During 1 829 070.1 person-years of follow-up, 336 CVD deaths were identified. After adjustment for potential confounders, multivariable-adjusted hazard ratios (95% CIs) for CVD mortality comparing PSA quartiles 2, 3, and 4 to the lowest quartile were 0.90 (0.66-1.22), 0.79 (0.58-1.08), and 0.69 (0.51-0.93), respectively. Serum total PSA levels within the reference range showed an inverse association with subclinical atherosclerosis and CVD mortality in young and middle-aged Korean men, indicating a possible role of PSA as a predictive marker for subclinical and clinical CVD.

The combination of AroCell TK 210 ELISA with Prostate Health Index or prostate-specific antigen density can improve the ability to differentiate prostate cancer from noncancerous conditions.

Prostate-specific antigen (PSA) is an established tumour marker for prostate cancer (PCa). Serum thymidine kinase 1 is a possible new marker for the detection of PCa. The aim of the study was to investigate the diagnostic value of the AroCell TK 210 enzyme-linked immunosorbent assay (ELISA) together with free PSA, [-2]proPSA, and Prostate Health Index (PHI) in differentiating PCa from benign urological conditions. Serum samples from 140 patients with PSA values in the range between 2 and 10 µg/L were collected at the Ljubljana University Medical Centre and the Maribor University Medical Centre. Thymidine kinase (TK1) protein levels were determined using the AroCell TK 210 ELISA and PSA-related parameters analysed with commercial assays. Serum TK1 protein, total and free PSA, proPSA, PSA density (PSAD), and PHI levels in patients with confirmed PCa were significantly higher than in patients with benign urological conditions (P < 0.05). Overall, the AroCell TK 210 ELISA results showed a significant correlation with PHI ( r = 0.25, P = 0.0031). Receiver-operating characteristic curve analyses were used to compare the area under the curve (AUC) of TK 210 ELISA, PHI, and PSA density. For PHI, the AUC was 0.73, comparable to those of TK 210 ELISA (0.67) and PSAD (0.66), with no significant differences in pairwise comparisons (PHI vs TK 210 ELISA P = 0.32, PHI vs PSAD P = 0.24, and TK 210 ELISA vs PSAD P = 0.95). The AUC for the combination of TK1 plus PSAD was significantly higher than those for the individual PSA-related biomarkers and marginally PHI, while the AUC for the combination of TK1 plus PHI was significantly higher than those for the individual PSA-related biomarkers except for PHI and marginally for PSAD. Total PSA concentration was the only marker, that was significantly higher in patients with an increasing Gleason grade. These results suggest that TK1 protein determinations together with PHI or PSAD could be a valuable additional tool in PCa management.

Expression and clinical significance of Caveolin-1 in prostate Cancer after transurethral surgery

BackgroundProstate cancer is a common malignancy of the male genitourinary system that occurs worldwide. The current research aims to investigate caveolin-1 expression in prostate cancer tissue and its relationship with pathological grade, clinical pathologic staging, and preoperative prostate-specific antigen (PSA) levels.MethodsFrom January 2012 to December 2014, samples from 47 patients with prostate cancer who had received transurethral prostatic resection (TURP) and 20 patients with benign prostatic hyperplasia were collected at the First Affiliated Hospital of Guangxi Medical University. Caveolin-1 was detected by streptavidin-perosidase (SP) immunohistochemical staining in pathological tissue slices. The results were statistically analyzed for pathological grade, clinical stage, and preoperative PSA level.ResultsThe expression of caveolin-1 was significantly higher in prostate cancer samples than in benign prostatic hyperplasia samples (P < 0.05), and caveolin-1 expression was significantly different among the pathological grades of poorly, moderately and well-differentiated prostate cancer (P < 0.05). The difference in caveolin-1 expression was significant for different clinical stages (T1-T2 and T3-T4) of prostate cancer (P < 0.05). The difference in caveolin-1 expression was not significant among samples with different preoperative PSA levels (0–10, 10–100 and > 100 μg/L) (P > 0.05).ConclusionsCaveolin-1 is closely related to the pathological grade and clinical stage of prostate cancer after transurethral surgery, and it may be a novel tumor marker for prostate cancer. The expression of caveolin-1 is not associated with preoperative serum PSA levels.

Prostate Specific Antigen Values of Geriatric Individuals Visiting a Tertiary Care Hospital in Southern India for Comprehensive Check Up

Prostate Specific Antigen (PSA) has become the most commonly used tumour marker for prostate cancer. Studies have suggested that age specific cutoff values for PSA screening are better than the currently used standard cutoff of 4.0ng/ml and different races have their own reference ranges. The objective of this study was to measure the PSA values of elderly individuals attending a tertiary care centre in southern India and postulate the possible normal values of PSA in different age groups of elderly. A total of 1038 males over the age of 60 years presenting to the Elderly Comprehensive Health clinic at the Department of Geriatrics of a tertiary hospital in Southern India between March 2009 and February 2011were studied. 4ml blood was collected and PSA was estimated by Chemiluminiscent Micro-particle Immunoassay. PSA values were analyzed in terms of mean, standard deviation and 5th and 95th percentiles. Results showed that 5th and 95th percentile values were 0.27 and 3.82 among those who were 60-69 years, 0.28 and 3.43 among those who were 70-79 years and 0.26 and 3.95 among those who were more than 80 years. 10 % of the elderly population in all age subsets had PSA values over the normal. This study showed that the PSA values from South India are similar to the expected. The age specific Indians being ethnically distinct, need to have separate PSA reference ranges which need to be established with large community-based multicentre Indian studies.

The Diagnostic Significance of Serum Alcohol Dehydrogenase Isoenzymes and Aldehyde Dehydrogenase Activity in Prostate Cancer Patients.

The aim of this study was to investigate a potential role of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) as tumor markers for prostate cancer (PCa). Serum samples were obtained from 52 patients with PCa, 34 patients with benign prostatic hyperplasia (BPH) and 60 healthy subjects. Class III and IV of ADH and total ADH activity were measured by the photometric method. For measurement of class I and II ADH and ALDH activity, the fluorometric method was employed. Significantly higher total activity of ADH, ADH III and ADH IV were found in the sera of both, PCa and BPH patients compared with healthy individuals. The diagnostic sensitivity for ADH III activity was 94.2%, specificity 100%, PPV (positive predictive value) and NPV (negative predictive value) were 100% and 95.2% respectively. Area under receiver-operating characteristics (ROC) curve for ADH III activity was 0.993. The results suggest a potential role of ADH III activity as a parameter included in the panel of markers for PCa.

Abstract 1476: Cell-free miR-141 as a molecular marker for prostate cancer metastasis

Abstract Prostate cancer is the second most commonly diagnosed neoplasia in men. Currently, there is no available non-invasive tool to assist in the identification of the aggressive form of this disease. Cell-free nucleic acid has been tested as a potential new molecular tool that can be useful in the diagnosis and prognosis of prostate cancer. MicroRNAs are a class of non-coding RNAs, that are shown to impact the development and progression of prostate cancer and their detection in plasma have been indicated as a promising non-invasive tool for disease screening and prognosis assessment. Among the several deregulated miRNAs that are observed in prostate cancer, the miRNA-141-3p was observed with upregulated expression levels in prostate cancer, particularly in the metastatic lesions. Therefore, the main aim of this study was to verify the diagnostic potential of miR-141 as a circulating tumor marker for prostate cancer and determine its functional role in modulating tumorigenesis in prostate cancer metastatic cell lines. MiR-141 expression analysis was performed in plasma samples of 102 prostate cancer patients without treatment and of 50 health controls by RT-qPCR. The experimental assays were performed by transfecting the PC3 cell line using miRNA-141 mimic/ inhibitor systems and directly accessing their effect in classical tumor phenotypes. Expression of the miR-141 were found significantly upregulated in the metastatic patients’ plasma specimens (FC=9.11, p=0.04; AUC=0.66) when compared to the patients without metastasis, showing its screening potential for prostate cancer metastasis. The in vitro ectopic expression of miR-141 in PC3 cell line showed a significant increased in cell proliferation, associated with changes in cell cycle (decreased number of cells in the G1 phase). Conversely, the inhibition of miR-141 showed an increase in the migratory ability, cell adhesion and in the Docetaxel cytotoxicity of the PC3 cells. Western-blot analysis showed that the inhibition of the miR-141 levels reduced the expression of the EMT inducers markers E-CADHERIN and CLAUDIN, and up-regulated the levels of ZEB-1, pAKT and VIMENTIN, consistent with their repression roles in the EMT process. These findings showed that miR-141 presents a direct function in controlling some of the in vitro metastatic phenotypes in prostate cancer, through the regulation of the epithelial-mesenchymal transition expression proteins. In conclusion, miR-141 presents a potential use as a minimally invasive molecular marker for prostate cancer diagnosis and can be used as a druggable target for therapy, particularly in the metastatic clinical setting. Citation Format: Marilesia Ferreira de Souza, Ilce Mara de Syllos Cólus, Aline Simoneti Fonseca, Hellen Kuasne, Paulo Emilio Fuganti, Deepak Kumar, Silvia Regina Rogatto, Luciane Regina Cavalli. Cell-free miR-141 as a molecular marker for prostate cancer metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1476. doi:10.1158/1538-7445.AM2017-1476

Urinary tumor markers in prostate cancer

Urinary tumor markers in prostate cancer

Evaluation of sHLA-G levels in serum of patients with prostate cancer identify as a potential of tumor marker.

Prostate cancer is the most common cancer type in men and is the second cause of death, due to cancer, in patients over 50, after lung cancer. Prostate specific antigen (PSA) is a widely used tumor marker for prostate cancer. Recently, PSA is discovered in non-prostatic cancer tissues in men and women raising doubts about its specificity for prostatic tissues. PSA exists in low serum level in healthy men and in higher levels in many prostate disorders, including prostatitis and prostate cancer. Thus, a supplementary tumor marker is needed to accurately diagnose the cancer and to observe the patient after treatment. Recently, soluble human leukocyte antigen-G (sHLA-G) has been introduced as a new tumor marker for different cancer types, including colorectal, breast, lung, and ovary. The present descriptive-experimental study was carried out including patients with malignant prostate tumor, patients with benign prostate tumor, and a group of health men as the control group, as judged by an oncologist as well as a pathologist. After sterile blood sampling, sHLA-G was measured by enzyme-linked immunosorbent assay in each group. The data was then analyzed using one-way ANOVA. P≤0.05 was considered as statistically significant. The results showed that the mean of sHLA-G level was high in patients. Also, it was found that there was a significant difference in sHLA serum level between the three groups. The data revealed that sHLA-G can be a novel supplementary tumor marker in addition to PSA to diagnose prostate cancer.

Prostate-specific antigen rising in Iranian men in correlation with body mass index, fasting blood sugar and blood lipid profile.

Background Prostate-specific antigen (PSA) is a serine protease that is secreted by prostate cells and it is useful as a tumor marker for prostate cancer. Objectives In this study, the relationship between some of metabolic factors and serum PSA level was investigated. Materials and Methods In this cross-sectional study, patients with urinary symptoms or for screening of the prostate cancer (after 50 years of age or 40 years with a family history of prostate cancer), were evaluated. Collected data included metabolic syndrome factors such as cholesterol (Chol), triglycerides (TG), fasting blood sugar (FBS), and body mass index (BMI), serum PSA level, prostate volume and age. Results 481 patients were enrolled to this study with the average age of 60.69 ± 9.72 years and the average PSA level of 1.70 ng/ml. Data analysis showed that there was a significant relationship between serum PSA level with age (P < 0.001, r = 0.30) and prostate volume (P < 0.001, r = 0.29). There were not significant relationship between serum PSA level with TG (P = 0.57, r = 0.026), Chol (P = 0.57, r = -0.025), FBS (P = 0.054, r = 0.088), and BMI (P = 0.89, r = 0.006). Conclusions This study showed that, with increasing age and prostate volume, serum PSA level increased, and an increase in the levels of cholesterol, TG, FBS and BMI did not have significant effect on serum PSA level.

Clinical prospects of long noncoding RNAs as novel biomarkers and therapeutic targets in prostate cancer

The lack of sensitive and specific biomarkers for prostate cancer (PCa) has led to over-diagnosis and overtreatment with uncertain benefit. Therefore, biomarkers for early diagnosis that can distinguish aggressive from indolent tumors and that can detect metastatic or recurrent disease are needed. Long noncoding RNAs (lncRNAs) are non-protein-coding RNA species. lncRNAs are dysregulated in many diseases including PCa and are emerging as major players in cancer development. lncRNAs have several features that make then suitable as both biomarkers and therapeutics, and lncRNAs regulate critical cancer hallmarks in prostate epithelial cells including proliferation and survival. The PubMed database was searched using the terms 'long noncoding RNA', 'biomarker' and 'prostate cancer'. Known lncRNAs implicated as biomarkers and potential therapeutic targets in PCa are reviewed. We comprehensively review several lncRNAs with potential as biomarkers for PCa. lncRNAs including PCA3, PCATs, SChLAP1, SPRY4-IT1 and TRPM2-AS are upregulated in PCa and are cancer specific; they are, therefore, attractive lead candidate biomarkers for clinical application. Several lncRNA therapeutics are currently being investigated by several companies for the treatment of various cancers including PCa. Small interfering RNAs, antisense oligonucleotides, ribozymes, deoxyribozymes and aptemers are few promising technologies for future lncRNA bases therapeutics. lncRNA expression is altered in cancer. Aberrant regulation promotes tumor formation, progression and metastasis. lncRNAs can use as tumor markers for PCa and may be attractive novel therapeutic targets for the diagnosis and treatment of PCa.

Prostate Specific Antigen as a Tumor Marker in Prostate Cancer: Biochemical and Clinical Aspects.

In this chapter the use of prostate specific antigen (PSA) as a tumor marker for prostate cancer is discussed. The chapter provides an overview of biological and clinical aspects of PSA. The main drawback of total PSA (tPSA) is its lack of specificity for prostate cancer which leads to unnecessary biopsies. Moreover, PSA-testing poses a risk of overdiagnosis and subsequent overtreatment. Many PSA-based markers have been developed to improve the performance characteristics of tPSA. As well as different molecular subforms of tPSA, such as proPSA (pPSA) and free PSA (fPSA), and PSA derived kinetics as PSA-velocity (PSAV) and PSA-doubling time (PSADT). The prostate health index (phi), PSA-density (PSAD) and the contribution of non PSA-based markers such as the urinary transcripts of PCA3 and TMPRSS-ERG fusion are also discussed. To enable further risk stratification tumor markers are often combined with clinical data (e.g. outcome of DRE) in so-called nomograms. Currently the role of magnetic resonance imaging (MRI) in the detection and staging of prostate cancer is being explored.

A case of metastatic cancer with markedly elevated PSA level that was not detected by repeat prostate biopsy

BackgroundProstate-specific antigen (PSA) is a widely used specific tumor marker for prostate cancer. We experienced a case of metastatic prostate cancer that was difficult to detect by repeat prostate biopsy despite a markedly elevated serum PSA level.Case presentationA 64-year-old man was referred to our hospital with lumbar back pain and an elevated serum PSA level of 2036 ng/mL. Computed tomography, bone scintigraphy, and magnetic resonance imaging showed systemic lymph node and osteoblastic bone metastases. Digital rectal examination revealed a small, soft prostate without nodules. Ten-core transrectal prostate biopsy yielded negative results. Androgen deprivation therapy (ADT) was started because of the patient’s severe symptoms. Twelve-core repeat transrectal prostate biopsy performed 2 months later, and transurethral resection biopsy performed 5 months later, both yielded negative results. The patient refused further cancer screening because ADT effectively relieved his symptoms. His PSA level initially decreased to 4.8 ng/mL, but he developed castration-resistant prostate cancer 7 months after starting ADT. He died 21 months after the initial prostate biopsy from disseminated intravascular coagulation.ConclusionCUP remains a considerable challenge in clinical oncology. Biopsies of metastatic lesions and multimodal approaches were helpful in this case.

Metastatic prostate cancer with elevated serum levels of CEA and CA19-9

Prostate-specific antigen (PSA) is well known as a specific tumor marker for prostate cancer, but carcinoembryonic antigen (CEA)- and carbohydrate antigen 19-9 (CA19-9)-elevating adenocarcinomas originating in the prostate gland are rare. We report a case of metastatic adenocarcinoma of the prostate gland with a high serum level of CEA and CA19-9 in a 78-year-old man in whom prostate cancer (T3N1M1) had been diagnosed 2 years ago and who was treated with androgen deprivation therapy. He visited the emergency department because of a loss of appetite and abdominal pain. The serum CEA and CA19-9 levels were increased to 218.9ng/mL (normal, <5ng/mL) and 212ng/mL (normal, <27ng/mL), respectively. The serum PSA level was slightly elevated (4.41ng/mL). Computed tomography demonstrated multiple liver metastases, para-aortic lymph node enlargement, and lung metastases. A liver biopsy was performed and the specimen showed high-grade adenocarcinoma with focal positive staining for PSA. Despite chemotherapy with docetaxel, the patient died 3 months after treatment. Based on this case and a review of the literature, an aggressive variant of prostatic carcinoma with a high serum level of CEA and CA19-9 and a low PSA level was shown to progress rapidly with a poor prognosis.

Interlaboratory study on differential analysis of protein glycosylation by mass spectrometry: the ABRF glycoprotein research multi-institutional study 2012.

One of the principal goals of glycoprotein research is to correlate glycan structure and function. Such correlation is necessary in order for one to understand the mechanisms whereby glycoprotein structure elaborates the functions of myriad proteins. The accurate comparison of glycoforms and quantification of glycosites are essential steps in this direction. Mass spectrometry has emerged as a powerful analytical technique in the field of glycoprotein characterization. Its sensitivity, high dynamic range, and mass accuracy provide both quantitative and sequence/structural information. As part of the 2012 ABRF Glycoprotein Research Group study, we explored the use of mass spectrometry and ancillary methodologies to characterize the glycoforms of two sources of human prostate specific antigen (PSA). PSA is used as a tumor marker for prostate cancer, with increasing blood levels used to distinguish between normal and cancer states. The glycans on PSA are believed to be biantennary N-linked, and it has been observed that prostate cancer tissues and cell lines contain more antennae than their benign counterparts. Thus, the ability to quantify differences in glycosylation associated with cancer has the potential to positively impact the use of PSA as a biomarker. We studied standard peptide-based proteomics/glycomics methodologies, including LC-MS/MS for peptide/glycopeptide sequencing and label-free approaches for differential quantification. We performed an interlaboratory study to determine the ability of different laboratories to correctly characterize the differences between glycoforms from two different sources using mass spectrometry methods. We used clustering analysis and ancillary statistical data treatment on the data sets submitted by participating laboratories to obtain a consensus of the glycoforms and abundances. The results demonstrate the relative strengths and weaknesses of top-down glycoproteomics, bottom-up glycoproteomics, and glycomics methods.

Label-free electrochemical immunosensor for prostate-specific antigen based on silver hybridized mesoporous silica nanoparticles

Due to high sensitivity and good selectivity, electrochemical immunosensor is often used to detect tumor markers. Prostate-specific antigen (PSA) is the most validated tumor marker for prostate cancer. In this work, mesoporous silica nanoparticles (MSNs) were used to increase the fixation capacity of primary antibody, and silver nanoparticles (Ag NPs) were used to enhance the electron transfer rates. Silver hybridized mesoporous silica nanoparticles (Ag@MSNs) were synthesized and used as electrode material. Hydroquinone (HQ) generated a stable electrochemical signal and was used as a mediator. Based on the specific antibody–antigen interaction, a label-free immunosensor was developed for the sensing of PSA. The current method allows us to detect PSA over a wide concentration range from 0.05 to 50.0ngml−1 with a detection limit of 15pgml−1. The proposed immunosensor was used to determine PSA in human serum with satisfactory results.