Potential Biomarker For Prostate Cancer Research Articles

Identification of Plasma Glycosphingolipids as Potential Biomarkers for Prostate Cancer (PCa) Status.

Prostate cancer (PCa) is the most common male cancer and the second leading cause of cancer death in United States men. Controversy continues over the effectiveness of prostate-specific antigen (PSA) for distinguishing aggressive from indolent PCa. There is a critical need for more specific and sensitive biomarkers to detect and distinguish low- versus high-risk PCa cases. Discovery metabolomics were performed utilizing ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) on plasma samples from 159 men with treatment naïve prostate cancer participating in the North Carolina-Louisiana PCa Project to determine if there were metabolites associated with aggressive PCa. Thirty-five identifiable plasma small molecules were associated with PCa aggressiveness, 15 of which were sphingolipids; nine common molecules were present in both African-American and European-American men. The molecules most associated with PCa aggressiveness were glycosphingolipids; levels of trihexosylceramide and tetrahexosylceramide were most closely associated with high-aggressive PCa. The Cancer Genome Atlas was queried to determine gene alterations within glycosphingolipid metabolism that are associated with PCa and other cancers. Genes that encode enzymes associated with the metabolism of glycosphingolipids were altered in 12% of PCa and >30% of lung, uterine, and ovarian cancers. These data suggest that the identified plasma (glyco)sphingolipids should be further validated for their association with aggressive PCa, suggesting that specific sphingolipids may be included in a diagnostic signature for PCa.

Differential profiling of prostate tumors versus benign prostatic tissues by using a 2DE-MALDI-TOF-based proteomic approach.

Oncoproteomic technologies offer a complementary approach to the understanding of cancer proteins' function and the translation of molecular knowledge into clinical practice. Our aim was to compare the proteomic profiles of prostate tumors versus benign prostatic hyperplasia (BPH) tissues in order to identify modulated proteins as the potential biomarkers for prostate cancer. Proteins extracted from twenty prostate cancer tissue specimens and ten BPH tissues were analyzed by two-dimensional electrophoresis (2-DE) coupled with MALDI-TOF mass spectrometry. Western blot and quantitative real-time PCR (RT-PCR) were performed to confirm the different amounts of protein biomarkers revealed by 2DE combined with MALDI mass spectrometry. We found 42 spots whose expression in the prostate was altered more than 1.5-fold compared with BPH tissue (p<0.05). These spots represented ten different proteins that were identified by a database search after mass spectrometry: they comprised proteins involved in the regulation of actin dynamics, the cytoskeleton, and cell motility (ACTG2, ACTA2, TPM1, DES, VIM, FLNA, and TAGLN), heat shock protein-27 (Hsp27), and proteins with other functions (TR and RANBP3). Subsequent western blot and RT-PCR assays for DES, VIM, TAGLN, and Hsp27 in prostate tumor tissues and BPH tissues confirmed the observations obtained by proteomic analysis. The cytoskeletal and cytoskeleton-associated proteins identified by this approach might be useful molecular targets for prostate cancer diagnostics and may contribute to novel therapies for prostate cancer.

PMEPA1 Gene Isoforms: A Potential Biomarker and Therapeutic Target in Prostate Cancer

The identification of prostate transmembrane protein androgen induced 1 (PMEPA1), an androgen responsive gene, came initially from the studies of androgen regulatory gene networks in prostate cancer. It was soon followed by the documentation of the expression and functional analysis of transmembrane prostate androgen-induced protein (TMEPAI)/PMEPA1 in other solid tumors including renal, colon, breast, lung, and ovarian cancers. Further elucidation of PMEPA1 gene expression and sequence analysis revealed the presence of five isoforms with distinct extracellular domains (isoforms a, b, c, d, and e). Notably, the predicted amino acid sequences of PMEPA1 isoforms show differences at the N-termini, a conserved membrane spanning and cytoplasmic domains. PMEPA1 serves as an essential regulator of multiple signaling pathways including androgen and TGF-β signaling in solid tumors. Structure-function studies indicate that specific motifs present in the cytoplasmic domain (PY, SIM, SH3, and WW binding domains) are utilized to mediate isoform-specific functions through interactions with other proteins. The understanding of the “division of labor” paradigm exhibited by PMEPA1 isoforms further expands our knowledge of gene’s multiple functions in tumorigenesis. In this review, we aim to summarize the most recent advances in understanding of PMEPA1 isoform-specific functions and their associations with prostate cancer progression, highlighting the potentials as biomarker and therapeutic target in prostate cancer.

Abstract 748: The small leucine-rich proteoglycan fibromodulin is a potential, novel serum and urinary biomarker for the detection of prostate cancer

Abstract Background: Prostate cancer (PCa) is the most common malignant tumor diagnosed in males and the fifth leading cause of cancer deaths worldwide. The impact of this cancer in the population is due, in part, to the lack of satisfactory methods for early diagnosis and accurate prognosis, which results in delayed clinical treatment of patients. Effective therapy exists for early stages, but it is practically incurable in advanced stages. Therefore, new and better molecular biomarkers are urgently needed for the opportune diagnosis and adequate prediction of the clinical course of the disease. We have previously identified the small leucine-rich proteoglycan, fibromodulin, as a novel, potential tissue biomarker for prostate cancer. Fibromodulin is a secreted proteoglycan which can be detected in different body fluids, such as blood, urine, or prostatic secretions. The aim of the present study was to determine whether fibromodulin concentration in serum and/or urine is able to differentiate PCa patients from patients with benign disease. Methods: Serum and urine samples were collected from a cohort of patients newly diagnosed with PCa (n=44) or with other prostatic disorders (n=46). Samples were also obtained from a group of control healthy individuals within the same age range. The concentration of fibromodulin in the blood and urine samples was measured with a commercial ELISA kit. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of fibromodulin in serum and urine. This work was approved by the Institutional Review Board of the University of Cartagena. Results: Both serum and urinary levels of fibromodulin were significantly higher in PCa patients compared to patients with benign disorders and healthy controls (p&amp;lt;0.05). Overall, urinary levels were higher than serum levels for each of the three groups. Conclusion: Our results support the potential of fibromodulin as a novel serum and urinary biomarker for PCa. Validation of these results requires prospective studies using a larger cohort of patients, as well as multicenter clinical trials, to define the real value of this protein as a biomarker for PCa. Keywords: Prostate cancer, fibromodulin, biomarkers, proteoglycan. Citation Format: Niradiz Reyes, Alfonso Bettin, Jan Geliebter. The small leucine-rich proteoglycan fibromodulin is a potential, novel serum and urinary biomarker for the detection of prostate cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 748.

Role of miRNA-182 and miRNA-187 as potential biomarkers in prostate cancer and its correlation with the staging of prostate cancer.

ABSTRACTPurpose The microRNAs expression has emerged as a potential biomarker for the diagnosis and prognosis of prostate cancer. This study investigated the expression of miRNA-182 and miRNA-187 in prostate cancer patients and established a correlation between miRNA expression and staging of prostate cancer.Materials and Methods This prospective observational study involved patients undergoing transrectal ultrasound-guided biopsy for suspicion of prostate cancer. Pre-biopsy urine samples and prostatic core tissue samples of the patients were preserved and the miRNA-182 and miRNA-187 were studied.Results Sixty-three patients were included in this study, thirty-three patients were diagnosed with prostate cancer and thirty patients having benign histopathology were considered as controls. The expression of miRNA-182 was significantly increased (p=0.002) and miRNA-187 significantly decreased (p <0.001) in prostate cancer tissue specimens. However, the expression of these miRNAs did not significantly differ in the urine of prostate cancer patients as compared to controls. Serum Prostatic Specific Antigen (PSA) inversely correlated with the median expression of miR-187 in prostatic tissue (p=0.002). Further, the expression of miRNA-187 in prostate cancer tissue was significantly decreased in metastatic prostate cancer (p=0.037). Using ROC analysis, miRNA-187 expression was able to distinguish the presence or absence of bone metastasis [area under ROC (AUROC) (±SD) was 0.873±0.061, p <0.001].Conclusion The miRNA-182 and miRNA-187 appear to be promising biomarkers in prostate cancer and miRNA-187 can serve as an important diagnostic marker of metastatic prostate cancer.

An Update on the Prognostic and Predictive Serum Biomarkers in Metastatic Prostate Cancer.

Serum biomarkers are molecules produced by normal and abnormal cells. Prostate specific antigen (PSA) is an example of a serum biomarker used widely in the diagnosis and prognostication of prostate cancer. PSA has its limitations as it is organ- but not cancer-specific. The aim of this review is to summarize the current published data on the potential prognostic and predictive biomarkers in metastatic prostate cancer (mPC) that can be used in conjunction with PSA. These biomarkers include microRNAs, androgen receptor variants, bone metabolism, neuroendocrine and metabolite biomarkers, and could guide treatment selection and sequence in an era where we strive to personalized therapy.

1050 - Serum N-glycan profiling is a potential biomarker for castration-resistant prostate cancer

1050 - Serum N-glycan profiling is a potential biomarker for castration-resistant prostate cancer

Assessment of expression levels of leptin and leptin receptor as potential biomarkers for risk of prostate cancer development and aggressiveness.

BackgroundProstate cancer (PCa) is one of the most frequently diagnosed cancers worldwide. Despite the growing evidence associating obesity and adipokines, particularly leptin and its receptors, with cancer development and progression, it is still a debatable matter in PCa.ObjectivesWe aimed to assess the role of leptin and its receptors as potential biomarkers for the risk of PCa development and aggressiveness.MethodsIn this study, 176 men were included and categorized according to an established histopathological diagnosis into three age‐ and BMI‐matched groups. The PCa group included 56 patients while the BPH group and the control group comprised 60 men each. Serum levels of total PSA (tPSA) were assessed by ELISA and mRNA expression levels of leptin and leptin receptors were assessed by RT‐PCR.ResultsLeptin and leptin receptor mRNA expression levels were significantly higher in PCa patients relative to BPH and to healthy control men. Both were overexpressed in PCa patients with aggressive and distantly metastasizing tumors compared to patients with confined tumors. Leptin receptor mRNA was an independent predictor of high Gleason score ≥ 7, distant metastasis, LN, and seminal vesicles invasion.ConclusionLeptin and its receptors are suggested to be potential biomarkers for PCa; leptin receptor mRNA might predict risk and aggressiveness of PCa.

LPAR1, Correlated With Immune Infiltrates, Is a Potential Prognostic Biomarker in Prostate Cancer.

Prostate cancer is a common malignancy in men worldwide. Lysophosphatidic acid receptor 1 (LPAR1) is a critical gene and it mediates diverse biologic functions in tumor. However, the correlation between LPAR1 and prognosis in prostate cancer, as well as the potential mechanism, remains unclear. In the present study, LPAR1 expression analysis was based on The Cancer Genome Atlas (TCGA) and the Oncomine database. The correlation of LPAR1 on prognosis was also analyzed based on R studio. The association between LPAR1 and tumor-infiltrating immune cells were evaluated in the Tumor Immune Estimation Resource site, ssGSEA, and MCPcounter packages in R studio. Gene Set Enrichment Analysis and Gene Ontology analysis were used to analyze the function of LPAR1. TCGA datasets and the Oncomine database revealed that LPAR1 was significantly downregulated in prostate cancer. High LPAR1 expression was correlated with favorable overall survival. LPAR1 was involved in the activation, proliferation, differentiation, and migration of immune cells, and its expression was positively correlated with immune infiltrates, including CD4+ T cells, B cells, CD8+ T cells, neutrophils, macrophages, dendritic cells, and natural killer cells. Moreover, LPAR1 expression was positively correlated with those chemokine/chemokine receptors, indicating that LPAR1 may regulate the migration of immune cells. In summary, LPAR1 is a potential prognostic biomarker and plays an important part in immune infiltrates in prostate cancer.

Abstract B044: PVT1 exons 4A and 4B overexpressed in prostate cancer in black males regulate prostate epithelial cell proliferation and migration

Abstract Prostate cancer (PCa) is the second most common cause of cancer-specific deaths in the United States, accounting for approximately 13% of cancer-related deaths. PCa is also the leading cancer in terms of incidence and mortality in men from Africa and the Caribbean. PCa is a multifactorial, complex disease, with the exact mechanisms for its development and progression unclear. Understanding the molecular mechanisms underlying the development and progression of PCa is necessary. This will aid in the discovery of novel and efficacious biomarkers with applications in early PCa detection and molecular therapeutic targeting. The non-protein coding gene locus Plasmacytoma Variant Translocation (PVT1) is located at 8q24 and is overexpressed in PCa. PVT1 has at least 12 exons that make separate transcripts having different functions. We have recently shown that PVT1 exons 4A and 4B are significantly overexpressed in prostate cancer tissues of Black males and are potential clinical biomarkers for prostate cancer in Black males. In this study, the role of PVT1 exons 4A and 4B in the migration and proliferation of prostate epithelial cells was examined. PVT1 exons 4A and 4B gene fragments were cloned into plasmid expression vectors and transfected into the RWPE1 prostate epithelial cell line to examine their effect on prostate epithelial cell proliferation and migration. We observed that overexpression of either PVT1 exon 4A, or PVT1 exon 4B significantly increased prostate epithelial cell migration and proliferation. This indicates that PVT1 exons 4A and 4B are functional biomarkers for prostate cancer. Better understanding of the roles of PVT1 exons 4A and 4B in PCa may lead to the future possibility of exploiting them for diagnosis, therapy, and other clinical applications in PCa. Citation Format: Gargi Pal, Olorunseun Ogunwobi. PVT1 exons 4A and 4B overexpressed in prostate cancer in black males regulate prostate epithelial cell proliferation and migration [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B044.

One-pot synthesized gold nanoparticle-peptide nanotube modified disposable sensor for impedimetric recognition of miRNA 410

In the presented study, gold nanoparticle assembled peptide nanotube (AuNP-PNT) modified graphite sensor system was offered for the first time for the impedimetric analysis of a potential prostate cancer biomarker, circulating miRNA 410, which is secreted by prostate cancer cells and is released into peripheral blood system. The proposed disposable sensor platform was easily constructed through one-pot synthesized nanocomposite modification with physical adsorption. AuNP-PNT nanocomposite and sensor surface features were identified with physicochemical, microscopic and electrochemical methods. The parameters which affect the sensor performance such as nanocomposite adsorption, probe DNA immobilization and hybridization process time-temperature were investigated and optimized. High sensitivity and low detection limit were established as 3.90 fM with a wide linear range from 10 fM to 300 pM for the impedimetric recognition of miRNA 410 based on the hybridization process. Selectivity experiment results proved that the developed surface captured the target miRNA with good base discrimination ability. Furthermore, the fabricated disposable sensor system was successfully applied in peripheral serum with good recovery. The proposed sensor system with its outstanding features such as cheapness, easiness, time effectiveness and sensitivity can be applied as a new sensor surface for the electrochemical detection of important analytes.

Overexpression of SOX4 induces up-regulation of miR-126 and miR-195 in LNCaP prostate cancer cell line

The present study aims to investigate the association between SOX4, Wnt signaling, and miRNAs under Wnt3 induction via bioinformatics analysis and functional essays. To briefly explore the expression of SOX4 protein in various types of cancer, we used ONCOMINE, a highly reputable cancer database, for comparison of its expression in prostate carcinoma relative to normal prostate gland. Concomitantly, we used CCLE to plot the copy number of SOX4 against its mRNA expression status in various cancerous cell lines to confirm the carcinogenesis role of SOX4. Afterward, whole profiling expression of microRNA in SOX4-stably expressed LNCaP cell line under the effect of Wnt3A were demonstrated. After identifying microRNA targets, STRING database and MIROB were used to explore the functional connection between proteins and microRNA with proteins. The results from our study shows that over-expressed of SOX4 was confirmed in both carcinogenesis tissue and cancer cell lines in Oncomine and CCLE database. In addition, five miRNAs, miR-16, miR-19a, miR320, miR-195, and miR-126, were differentially expressed in LNCaP cell line induced by Wnt3a. Pathway analysis of these targets proposed interaction networks of SOX4, Wnt3a with miR-126 and miR-195. Altogether, the miRNAs involved in Wnt and SOX4-mediated prostate cancer such as miR-126 and miR-195 could be potential biomarkers in prostate cancer.

Ultrasensitive Ti3C2TX MXene/Chitosan Nanocomposite-Based Amperometric Biosensor for Detection of Potential Prostate Cancer Marker in Urine Samples.

Two-dimensional layered nanomaterial Ti3C2TX (a member of the MXene family) was used to immobilise enzyme sarcosine oxidase to fabricate a nanostructured biosensor. The device was applied for detection of sarcosine, a potential prostate cancer biomarker, in urine for the first time. The morphology and structures of MXene have been characterised by atomic force microscopy (AFM) and scanning electron microscopy (SEM). Electrochemical measurements, SEM and AFM analysis revealed that MXene interfaced with chitosan is an excellent support for enzyme immobilisation to fabricate a sensitive biosensor exhibiting a low detection limit of 18 nM and a linear range up to 7.8 µM. The proposed biosensing method also provides a short response time of 2 s and high recovery index of 102.6% for detection of sarcosine spiked into urine sample in a clinically relevant range.

B7-H4 is a potential prognostic biomarker of prostate cancer

B7-H4 is a member of B7 family which regulates immune responses by delivering costimulatory signals. However, it negatively regulates T cell-mediated immunity and may play an important role in tumor immune evasion. Although several studies have been reported that expression of B7-H4 is elevated in the several types of human cancer with a poor clinical outcome, its clinical significance in the prostate cancer (PCa) has not been well studied. In this study, we investigated the clinical significance of B7-H4 in human PCa and determined if B7-H4 expression is associated with the cancer cell stemness in PCa. Our studies show that expression of B7-H4 is correlated with the pathologic tumor (pT) stage and the clinical stage of PCa. The Kaplan-Meier survival analysis revealed that PCa patients with high expression of B7-H4 exhibits a shorter overall survival (OS) rate. Univariate and multivariate Cox regression analysis indicated that B7-H4 is an independent poor prognostic factor of PCa. In addition, the expression of B7-H4 is correlated with the cancer cell stemness associated genes expression in PCa. Further, our studies show that B7-H4 regulates cancer cell stemness associated genes expression and effects on the cell cycle and PI3K/Akt signaling related genes expression in PCa. These results indicate that B7-H4 expression is associated with cancer cell stemness, and B7-H4 is a potential prognostic biomarker and a therapeutic target of PCa.

Copy number amplification of androgen receptor in cell-free DNA is a potential prognostic factor in patients with CRPC.

180 Background: A circulating cell-free DNA (cfDNA) has been suggested as a potential biomarker for castration-resistant prostate cancer (CRPC). However, clinical implication of the parameters in cfDNA remains unclear. We aimed to investigate the impact of copy number variation (CNV) of androgen-receptor amplification (AR-amp) in cfDNA on prognosis in patients with CRPC. Methods: We retrospectively evaluated AR-amp in cfDNA in 154 patients with prostate cancer between April 2018 and September 2019. We compared AR-amp between the patients with CRPC and non-CRPC. An optimal cutoff point was defined using receiver operating characteristic (ROC) curve. The effect of AR-amp on prognosis was evaluated between the CRPC patients with AR-amp high and low. Results: The median age and initial PSA was 75 years and 34 ng/mL, respectively. The number of patients with abiraterone acetate, enzalutamide, docetaxel, cabazitaxel was 24, 15, 21, and 2, respectively. No significant association was observed between the AR-amp and serum prostate-specific antigen (PSA) level at AR-amp measurement. Of 154, 73 (47%) patients developed to CRPC. The AR-amp was significantly higher in the patients with CRPC than that in the non-CRPC (1.07 vs. 0.97, respectively, P&lt;0.001). The cutoff value of AR-amp was defined 1.16 with area under the ROC curve of 0.672. Overall survival was significantly shorter in the patients with AR-amp low (≤1.16, n=46) than that with AR-amp high (&gt;1.16, n=27) (8.9 vs. 9.6 months, respectively, P &lt; 0.001). The AR-amp was not significantly different between the pre- and post-docetaxel status in patients with CRPC. Conclusions: AR-amp in cfDNA might be a potential biomarker for poor prognosis in patients with CRPC who were treated with life-prolonging therapies.

Anti-tumor activities of Panax quinquefolius saponins and potential biomarkers in prostate cancer

BackgroundProstate carcinoma is the second most common cancer among men worldwide. Developing new therapeutic approaches and diagnostic biomarkers for prostate cancer (PC) is a significant need. The Chinese herbal medicine Panax quinquefolius saponins (PQS) have been reported to show anti-tumor effects. We hypothesized that PQS exhibits anti-cancer activity in human PC cells and we aimed to search for novel biomarkers allowing early diagnosis of PC. MethodsWe used the human PC cell line DU145 and the prostate epithelial cell line PNT2 to perform cell viability assays, flow cytometric analysis of the cell cycle, and FACS-based apoptosis assays. Microarray-based gene expression analysis was used to display specific gene expression patterns and to search for novel biomarkers. Western blot and quantitative real-time PCR were performed to demonstrate the expression levels of multiple cancer-related genes. ResultsOur data showed that PQS inhibited the viability of DU145 cells and induced cell cycle arrest at the G1 phase. A significant decrease in DU145 cell invasion and migration were observed after 24 h treatment by PQS. PQS up-regulated the expression levels of p21, p53, TMEM79, ACOXL, ETV5, and SPINT1 while it down-regulated the expression levels of bcl2, STAT3, FANCD2, DRD2, and TMPRSS2. ConclusionPQS promoted cells apoptosis and inhibited the proliferation of DU145 cells, which suggests that PQS may be effective for treating PC. TMEM79 and ACOXL were expressed significantly higher in PNT2 than in DU145 cells and could be novel biomarker candidates for PC diagnosis.

Development of micropillar array electrodes for highly sensitive detection of biomarkers.

Micropillar array electrodes (μAEs) have been widely applied in electrochemical detection owing to their advantages of increased mass transport, lower detection limit, and potential to be miniaturized. This paper reports the fabrication, simulation, surface modification, and characterization of PDMS-based μAEs coated with gold films. The μAEs consist of 9 × 10 micropillars with a height of either 100 μm, 300 μm, or 500 μm in a 0.09 cm2 region. Numerical simulation was employed to study the influence of geometrical parameters on the current density. The μAEs were fabricated by soft lithography and characterized using both SEM and cyclic voltammetry. Experiments revealed that high pillars enabled enhanced voltammetric current density regardless of the scan rates. The platinum–palladium/multi-walled carbon nanotubes (Pt–Pd/MWCNTs) were coated on the μAEs to improve their electrochemical detection capability. The μAEs demonstrated 1.5 times larger sensitivity compared with the planar electrode when hydrogen peroxide was detected. Furthermore, μAE500 with Pt–Pd/MWCNTs was employed to detect sarcosine, a potential biomarker for prostate cancer. The linear range and limit of detection for sarcosine were from 5 to 60 μM and 1.28 μM, respectively. This detection range covers the concentration of sarcosine in human tissues (0–60 μM). These results suggest that the μAEs have better detection performance in comparison to planar electrodes due to their large surface area and pillar height. This paper provides essential guidelines for the application of μAEs in high sensitivity electrochemical detection of low abundance analytes.

Serum N-glycan profiling is a potential biomarker for castration-resistant prostate cancer

We investigated the diagnostic and prognostic potential of serum N-glycan profiling for castration-resistant prostate cancer (CRPC). We retrospectively investigated serum N-glycan structural analysis by glycoblotting for 287 patients with benign prostatic hyperplasia (BPH), 289 patients with newly diagnosed prostate cancer (PC), 57 patients with PC treated with androgen-deprivation therapy without disease progression (PC-ADT), and 60 patients with CRPC. N-Glycan profiling was compared between the non-CRPC (BPH, newly diagnosed PC and PC-ADT) and CRPC patients. We obtained the quantitative score for CRPC (CRPC N-glycan score) by discriminant analysis based on the combination of 9 N-glycans that were significantly associated with CRPC. The median CRPC N-glycan score was found to be significantly greater in CRPC patients than in non-CRPC patients. The CRPC N-glycan score could classify CRPC patients with sensitivity, specificity, and area under the curve of 87%, 69%, and 0.88, respectively. The CRPC N-glycan score >1.7 points was significantly associated with poor prognosis in patients with CRPC. The glycoprotein analysis showed that not immunoglobulins but α-1-acid glycoprotein (AGP) were a potential candidate for the carrier protein of N-glycans. The overexpression of specific N-glycans may be associated with their castration-resistant status and be a potential biomarker for CRPC.

Molecular profiling of radical prostatectomy tissue from patients with no sign of progression identifies ERG as the strongest independent predictor of recurrence.

Background: As a major cause of morbidity and mortality among men, prostate cancer is a heterogenous disease, with a vast heterogeneity in the biology of the disease and in clinical outcome. While it often runs an indolent course, local progression or metastasis may eventually develop, even among patients considered “low risk” at diagnosis. Therefore, biomarkers that can discriminate aggressive from indolent disease at an early stage would greatly benefit patients. We hypothesized that tissue specimens from early stage prostate cancers may harbor predictive signatures for disease progression.Methods: We used a cohort of radical prostatectomy patients with longitudinal follow-up, who had tumors with low grade and stage that revealed no signs of future disease progression at surgery. During the follow-up period, some patients either remained indolent (non-BCR) or progressed to biochemical recurrence (BCR). Total RNA was extracted from tumor, and adjacent normal epithelium of formalin-fixed-paraffin-embedded (FFPE) specimens. Differential gene expression in tumors, and in tumor versus normal tissues between BCR and non-BCR patients were analyzed by NanoString using a customized CodeSet of 151 probes.Results: After controlling for false discovery rates, we identified a panel of eight genes (ERG, GGT1, HDAC1, KLK2, MYO6, PLA2G7, BICD1 and CACNAID) that distinguished BCR from non-BCR patients. We found a clear association of ERG expression with non-BCR, which was further corroborated by quantitative RT-PCR and immunohistochemistry assays.Conclusions: Our results identified ERG as the strongest predictor for BCR and showed that potential prognostic prostate cancer biomarkers can be identified from FFPE tumor specimens.

LacdiNAc-Glycosylated Prostate-specific AntigenDensity is a Potential Biomarker of ProstateCancer.

Serum LacdiNAc-glycosylated prostate-specific antigen (LDN-PSA) and LDN-PSA density together with PSA and PSA density (PSAD) were measured as a diagnostic tool for prostate cancer (PCa). We included 150 patients with PCa without hormonal therapy and 41 patients without PCa obtained from the Kyoto University Hospital between 2012 and 2017. LDN-PSA levels were measured through a WFA-anti-PSA antibody sandwich immunoassay using a highly sensitive surface plasmon field-enhanced fluorescence spectroscopy (SPFS) system. Diagnostic performance of serum LDN-PSA and LDN-PSAD was evaluated by measuring the area under the receiver-operating characteristic curve (AUC). The AUCs of LDN-PSA, LDN-PSAD, and PSAD levels (0.780, 0.848, and 0.835, respectively) detected in patients with PCa were significantly higher (P= .0001, P< .0001, and P< .0001, respectively) than that of PSA (0.590). Moreover, among 143 patients with PCa who received radical prostatectomy (RP), the AUCs of LDN-PSA, LDN-PSAD, and PSAD levels (0.750, 0.812, and 0.769, respectively) detected in patients with a pathologic Gleason grade group≥ 2 were significantly higher (P= .0170, P= .0028, and P= .0003, respectively) than that of PSA (0.578). In the group comprising 35 patients who received RP with a Gleason grade group 1-graded biopsy, the LDN-PSA, LDN-PSAD, and PSAD levels were significantly different (P= .0097, P= .0024, and P= .0312, respectively). However, PSA alone could not discriminate cases with adverse features (P= .454). LDN-PSAD is a potential marker for detecting PCa and selecting candidates for RP.