Marker For Prostate Cancer Research Articles

The value of a panel of circulating microRNAs in screening prostate cancer.

Prostate cancer (PCa) remains a worldwide public health problem that poses a serious threat to the health of men worldwide. Many studies have found that microRNA (miRNA) in serum has the potential to be a biomarker for cancer screening. Our study was conducted to investigate the value of serum miRNAs in PCa screening. We selected 12 miRNAs from past studies for its association with PCa. We checked the expression levels of these miRNAs in the serum of 112 PCa patients and 112 healthy controls in a two-stage experiment. We plotted the receiver operating characteristic curve of miRNAs in the validation stage and constructed a four-miRNA panel with the highest diagnostic value using stepwise logistic regression. We also predicted the target genes with these four miRNAs through online databases and performed Gene Ontology functional annotation and pathway analysis. The results showed that six miRNAs (miR-429, miR-10a-5p, miR-183-5p, miR-181a-5p, miR-1231, miR-129-5p) were abnormally expressed in the serum of PCa patients. We used four of these miRNAs including miR-1231, miR-10a-5p, miR-429 and miR-129-5p to construct a combination of miRNAs with high specificity and sensitivity in screening PCa (area under the curve =0.878). Bioinformatics analysis showed that the genes targeted by these miRNAs can be linked to the development of PCa. Our study detected and identified a set of miRNAs that serves as screening marker for PCa, which may assist in early diagnosis and treatment of PCa.

Microfluidic electrolyte-gated TiS3 nanoribbons-based field-effect transistor as ultrasensitive label-free immunosensor for prostate cancer marker analysis

Early detection of prostate cancer, the second main cause of death in men, with robust assay platforms by using the appropriate biomarkers is of great importance for diagnosis and follow-up of disease under treatment. The aim of this research is to investigate how novel TiS3 nanoribbons can be used as a channel material in the microfluidic electrolyte-gated field-effect transistor (FET), with the goal of developing a label-free immunosensor for the sensitive, selective, and rapid detection of PSA as a cancer marker in both PBS and human serum samples. To create an active channel material, the TiS3 nanoribbons were deposited onto the FET surface through a drop-casting process, and the surface of the channel was subsequently modified with an anti-PSA monoclonal antibody. The electrical properties of the microfluidic electrolyte-gated TiS3 nanoribbon-based FET were characterized, and the results showed that it exhibited a depletion-mode n-type behavior with a field-effect mobility of 2.3 × 10−3 cm2/Vs, an Ion/Ioff current ratio of 4.12, and a subthreshold swing (SS) of 914.1 mV/decade. As the concentration of PSA increased from 0.1 fg/mL to 10 pg/mL, there was a corresponding increase in the drain current with a high sensitivity of 2.2665 nA/decade and a detection limit of 0.04 fg/mL. Integrating the electrolyte-gated FET with the microfluidic channel resulted in improved performance of the microfluidic electrolyte-gated FET immunosensor. The combination of these two components led to better control and delivery of small sample volumes to the surface of the electrolyte-gated FET, which improved the repeatability of the obtained data. Based on the results obtained from the microfluidic immunosensor, it can be inferred that the developed platform has the potential to be an excellent candidate for point-of-care cancer diagnosis and therapeutic monitoring.

Bone Turnover Markers, n-Terminal Propeptide of Type I Procollagen and Tartrate-Resistant Acid Phosphatase Type 5b, for Predicting Castration Resistance in Prostate Cancer.

Bone is a common site of prostate cancer metastasis. Bone turnover markers n-terminal propeptide of type I procollagen (P1NP) and tartrate-resistant acid phosphatase type 5b (TRACP-5b) are highly sensitive to bone remodeling activity. However, their prognostic significance as markers of prostate cancer is unknown. This study retrospectively examined the usefulness of P1NP and TRACP-5b as prognostic biomarkers. Castration-resistant prostate cancer recurrence-free survival (CFS) was estimated using the Kaplan-Meier method. A predictive model for CFS was constructed using multivariate analysis. This study enrolled 255 patients diagnosed with prostate cancer at Kanazawa University Hospital. The median follow-up was 115.1 months. Patients with both high serum P1NP and TRACP-5b levels, defined as having a poor bone turnover category (BTC), had significantly shorter CFS. Multivariate analysis identified Gleason score, metastasis, and BTC poor as predictors for castration resistance in prostate cancer. Using these three factors, a prognostic model was established, categorizing patients into low-risk (no or one factor) and high-risk (two or three factors) groups. In the low-risk group, the median CFS was not reached, contrasting with 19.1 months in the high-risk group (hazard ratio, 32.23, p < 0.001). Combining P1NP and TRACP-5b may better predict castration resistance.

Prostein expression in human tumors: a tissue microarray study on 19,202 tumors from 152 different Tumor entities

BackgroundProstein (P501S), also termed solute carrier family 45 member 3 (SLC45A3) is an androgen regulated protein which is preferentially expressed in prostate epithelial cells. Because of its frequent expression in prostate cancer, prostein was suggested a diagnostic prostate cancer marker.MethodsIn order to comprehensively assess the diagnostic utility of prostein immunohistochemistry, a tissue microarray containing 19,202 samples from 152 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry.ResultsProstein immunostaining was typically cytoplasmic, granular and perinuclear. Prostein positivity was seen in 96.7% of 419 prostate cancers including 78.3% with strong staining. In 16,709 extra-prostatic tumors, prostein positivity was observed in 7.2% of all cases but only 0.3% had a strong staining. Overall, 50 different extra-prostatic tumor categories were prostein positive, 12 of which included at least one strongly positive case. Extra-prostatic tumors with highest rates of prostein positivity included different subtypes of salivary gland tumors (7.6-44.4%), neuroendocrine neoplasms (15.8-44.4%), adenocarcinomas of the gastrointestinal tract (7.3-14.8%), biliopancreatic adenocarcinomas (3.6-38.7%), hepatocellular carcinomas (8.1%), and adenocarcinomas of other organs (up to 21%).ConclusionsOur data provide a comprehensive overview on prostein expression in human cancers. Prostein is a highly sensitive prostate cancer marker occurring in > 96% of prostate cancers. Because prostein can also be expressed in various other tumor entities, classifying of a tumor mass as a prostate cancer should not be based on prostein positivity alone.

Parameters of Cell Death and Proliferation of Prostate Cancer Cells with Altered Expression of Myosin 1C Isoforms

Myosin 1C is a monomeric myosin motor with a truncated tail domain. Such motors are referred as slow “tension sensors.” Three isoforms of myosin 1C differ in short N-termed amino acid sequences, the functional differences between isoforms have not been elucidated. Myosin 1C isoform A was described as a diagnostic marker for prostate cancer, but its role in tumor transformation remains unknown. Based on data on the functions of myosin 1C, we hypothesized the potential role of myosin 1C isoforms in maintaining the tumor phenotype of prostate cancer cells. In our work, we showed that a decrease in the expression level of myosin 1C isoform C leads to an increase in the proliferative activity of prostate tumor cells.

High expression of Trop2 is associated with aggressive localized prostate cancer and is a candidate urinary biomarker

Distinguishing indolent from clinically significant localized prostate cancer is a major clinical challenge and influences clinical decision-making between treatment and active surveillance. The development of novel predictive biomarkers will help with risk stratification, and clinical decision-making, leading to a decrease in over or under-treatment of patients with prostate cancer. Here, we report that Trop2 is a prognostic tissue biomarker for clinically significant prostate cancer by utilizing the Canary Prostate Cancer Tissue Microarray (CPCTA) cohort composed of over 1100 patients from a multi-institutional study. We demonstrate that elevated Trop2 expression is correlated with worse clinical features including Gleason score, age, and pre-operative PSA levels. More importantly, we demonstrate that elevated Trop2 expression at radical prostatectomy predicts worse overall survival in men undergoing radical prostatectomy. Additionally, we detect shed Trop2 in urine from men with clinically significant prostate cancer. Our study identifies Trop2 as a novel tissue prognostic biomarker and a candidate non-invasive marker for prostate cancer.

Immunohistochemical Expression Status of HER2/neu and E-cadherin in Prostate Adenocarcinoma: A Cross-sectional Study

Introduction: Prostate cancer is a common tumour, accounting for 92% of malignancies in the male genital tract. Due to the high recurrence rate, it is important to identify prognostic markers in prostate cancer. Human Epidermal Growth Factor Receptor 2 (HER2) and Epithelial cadherin (E-cadherin) are speculated to be associated with carcinogenesis, but the literature has provided controversial results. Aim: To investigate the expression of HER2/neu and E-cadherin in prostatic adenocarcinoma and its correlation with clinicopathological parameters. Materials and Methods: A retrospective cross-sectional study was conducted at the Department of Pathology, SDM University, Dharwad, Karnataka, India. The study duration was one year and five months, from October 2020 to March 2022. A total of 45 cases diagnosed as prostatic adenocarcinoma between October 2016 and September 2019 were included. Clinicopathological parameters such as age, Prostate- Specific Antigen (PSA) levels, metastasis, perineural invasion, Gleason score, Gleason grade, and two-year survival were retrieved from hospital records and through telephone interviews. Immunohistochemistry (IHC) staining for HER2 and E-cadherin was performed and assessed by pathologists. Statistical analysis was conducted using Statistical Package for Social Sciences (SPSS) version 20.0, and the Chi-square test was applied. Results: The mean age of the study participants was 69.6 years, ranging from 52 to 95 years. The rates of HER2/neu overexpression/positivity and reduced E-cadherin expression were 25 (55.5%) and 14 (31.1%), respectively. No statistically significant associations were found between HER2 and E-cadherin expression and age, PSA levels, perineural invasion, Gleason score, Gleason grade, and two-year survival (p&gt;0.05). However, a statistically significant association was observed between HER2 expression and distant metastasis (p-value=0.006), whereas no significant association was found with E-cadherin (p-value=0.81). Conclusion: The study demonstrated a significant association between HER2/neu overexpression and tumour metastasis, suggesting that HER2/neu could serve as a prognostic parameter to assist surgeons. In contrast, E-cadherin showed no association with clinicopathological parameters, raising questions about its involvement in the progression of prostatic adenocarcinoma.

Prognostic significance of soluble PD-L1 in prostate cancer.

The aim of this study was to assess the role of sPD-L1 and sPD-1 as potential biomarkers in prostate cancer (PCa). The association of the values of these soluble proteins were correlated to the clinical data: stage of disease, Gleason score, biochemical recurrence etc. For a comprehensive study, the relationship between sPD-L1 and sPD-1 and circulating immune cells was further investigated. A total of 88 patients with pT2 and pT3 PCa diagnosis and 41 heathy men were enrolled. Soluble sPD-L1 and sPD-1 levels were measured in plasma by ELISA method. Immunophenotyping was performed by flow cytometry analysis. Our study's findings demonstrate that PCa patients had higher levels of circulating sPD-L1 and sPD-1 comparing to healthy controls (p < 0.001). We found a statistically significant (p < 0.05) relationship between improved progression free survival and lower initial sPD-L1 values. Furthermore, patients with a lower sPD-1/sPD-L1 ratio were associated with a higher probability of disease progression (p < 0.05). Additionally, a significant (p < 0.05) association was discovered between higher Gleason scores and elevated preoperative sPD-L1 levels and between sPD-1 and advanced stage of disease (p < 0.05). A strong correlation (p < 0.05), between immunosuppressive CD4+CD25+FoxP3+ regulatory T cells and baseline sPD-L1 was observed in patients with unfavorable postoperative course of the disease, supporting the idea that these elements influence each other in cancer progression. In addition to the postoperative drop in circulating PD-L1, the inverse relationship (p < 0.05), between the percentage of M-MDSC and sPD-L1 in patients with BCR suggests that M-MDSC is not a source of sPD-L1 in PCa patients. Our findings suggest the potential of sPD-L1 as a promising prognostic marker in prostate cancer.

Rho GTPase activating protein 21-mediated regulation of prostate cancer associated 3 gene in prostate cancer cell.

The overexpression of the prostate cancer antigen 3 (PCA3) gene is well-defined as a marker for prostate cancer (PCa) diagnosis. Although widely used in clinical research, PCA3 molecular mechanisms remain unknown. Herein we used phage display technology to identify putative molecules that bind to the promoter region of PCA3 gene and regulate its expression. The most frequent peptide PCA3p1 (80%) was similar to the Rho GTPase activating protein 21 (ARHGAP21) and its binding affinity was confirmed using Phage Bead ELISA. We showed that ARHGAP21 silencing in LNCaP prostate cancer cells decreased PCA3 and androgen receptor (AR) transcriptional levels and increased prune homolog 2 (PRUNE2) coding gene expression, indicating effective involvement of ARHGAP21 in androgen-dependent tumor pathway. Chromatin immunoprecipitation assay confirmed the interaction between PCA3 promoter region and ARHGAP21. This is the first study that described the role of ARHGAP21 in regulating the PCA3 gene under the androgenic pathway, standing out as a new mechanism of gene regulatory control during prostatic oncogenesis.

Fluorescein-switching-based lateral flow assay for the detection of microRNAs.

Lateral flow assays (LFAs) are a cost-effective and rapid colorimetric technology that can be effectively used for nucleic acid tests (NATs) in various fields such as medical diagnostics and biotechnology. Given their importance, developing more diverse LFAs that operate through novel working mechanisms is essential for designing highly selective and sensitive NATs and providing insights for designing various practical point-of-care testing (POCT) systems. Herein we report a new type of lateral flow assay (LFA) based on fluorescein-switching, enabled by nucleic acid-templated photooxidation of reduced fluorescein by riboflavin tetraacetate (RFTA). The LFA design leverages the fact that a reduced form of fluorescein, which weakly binds to gold nanoparticle (GNP)-conjugated anti-fluorescein antibodies, is oxidized in the presence of target nucleic acids to yield its native state, which then strongly binds to the antibodies. The study involved designing and optimizing probe sequences to detect miR-6090 and miR-141, which are significant markers for prostate cancer. To minimize background signals of LFAs, sodium borohydride (NaBH4) was specifically introduced as a reducing agent, and detailed procedures were established. The developed LFA system accurately identified low fmol levels of target microRNAs with minimal false positives, all detectable with the naked eye, making the system a promising tool for point-of-care diagnostics.

The effect of tumor composition on the success of adaptive therapy: The case of metastatic Castrate-Resistant Prostate Cancer.

Prostate-specific antigen (PSA) is the most commonly used serum marker for prostate cancer. It plays a role in cancer detection, treatment monitoring, and more recently, in guiding adaptive therapy protocols, where treatment is alternated based on PSA levels. However, the relationship between PSA levels and tumor volume remains poorly understood. Empirical evidence suggests that different cancer cell types produce varying amounts of PSA. Despite this, current mathematical cancer models often assume either that all cell types contribute equally to PSA levels or that only certain subpopulations produce PSA at fixed rates. In this study, we compare Zhang et al.'s classical adaptive therapy protocol with the standard of care, which involves continuous maximum tolerable dose treatment, under different assumptions regarding PSA production. Specifically, we explore the possibility that testosterone-dependent, testosterone-producing, and testosterone-independent cells contribute to PSA production to varying degrees. We use the time to competitive release as a proxy for the time to disease progression. Our findings indicate that adaptive therapy consistently results in a longer time to competitive release compared to the standard of care, regardless of the assumptions about PSA production. However, when testosterone-independent cells are the sole PSA producers, Zhang et al.'s adaptive therapy protocol becomes inapplicable, as PSA levels never fall to half of their initial value, preventing therapy discontinuation. Additionally, we observe that the number and duration of treatment cycles in adaptive therapy are highly sensitive to assumptions about how much each cell type contributes to PSA production. Overall, our results emphasize the need for a deeper understanding of patient-specific PSA dynamics, which could enhance the effectiveness of adaptive therapy in prostate cancer treatment.

Association of neighborhood gentrification with prostate cancer and immune markers in African American and European American men.

Prior studies showed that neighborhood deprivation increases the risk of lethal prostate cancer. However, the role of neighborhood gentrification in prostate cancer development and outcome remains poorly understood. We examined the relationships of gentrification with prostate cancer and serum proteome-defined inflammation and immune function in a diverse cohort. The case-control study included 769 cases [405 African American (AA), 364 European American (EA) men] and 1023 controls (479 AA and 544 EA), with 219 all-cause and 59 prostate cancer-specific deaths among cases. Geocodes were linked to a neighborhood gentrification index (NGI) derived from US Census data. Cox and logistic regression, and MANOVA, were used to determine associations between NGI, as continuous or quintiles (Q), and outcomes. Adjusting for individual socioeconomic status (SES), continuous NGI was positively associated with prostate cancer among all men (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.01-1.14). AA and low-income men experienced the highest odds of prostate cancer when residing in tracts with moderate gentrification, whereas EA men experienced reduced odds of regional/metastatic cancer with increased gentrification in SES-adjusted analyses. Continuous NGI also associated with mortality among men presenting with localized disease and low-income men in SES-adjusted Cox regression analyses. NGI was not associated with serum proteome-defined chemotaxis, inflammation, and tumor immunity suppression. Findings show that neighborhood gentrification associates with prostate cancer and mortality in this diverse population albeit associations were heterogenous within subgroups. The observations suggest that changing neighborhood socioeconomic environments may affect prostate cancer risk and outcome, likely through multifactorial mechanisms.

Triad of serum PSA, DRE and biopsy in diagnosing prostatic diseases- How useful it is?

Prostate specific antigen (PSA) is a glycoprotein produced by prostatic acini and prostatic tissue. Its concentration increases in prostatic diseases. Concentration above 4 ng/ml is considered abnormal but there is no clear-cut point between normal and abnormal PSA levels. PSA is considered as serum marker for prostatic cancer but it is organ specific, not cancer specific. Digital rectal examination (DRE) is a routine part of prostate cancer screening. Biopsies are performed when PSA test and DRE are abnormal. The study is an attempt for comparative analysis among serum PSA, age, DRE, and biopsy results for the institution of specific treatment at an early stage. Study was performed on 200 patients with different prostatic lesions in the Department of Pathology, Jawaharlal Nehru Medical College and Hospital, Aligarh Muslim University, Aligarh. Clinical, DRE, PSA and histopathological biopsy were performed and analyzed by correlating the data. In our study 77.5% had normal (0-4 ng/ml) PSA level and 13.5% had &amp;#62;10 ng/ml PSA levels. BPH was the most common diagnosis (54.0%), followed by prostatitis (20.0%), BPH with prostatitis in 16.0% and carcinoma (10.0%). Serum PSA with positive DRE ranged from 1.2 ng/ml to 56 ng/ml while in negative DRE ranged from 0.18 ng/ml to 9.6 ng/ml. PSA is specific for prostate but not for prostatic diseases. With increasing age serum PSA also increases. Conjunction of serum PSA with other variables like age, DRE and biopsy makes a better diagnosis of prostatic diseases.

Prostein expression on circulating tumor cells as a prognostic marker in metastatic castration-resistant prostate cancer.

Identification of emerging molecular biomarkers on circulating tumor cells (CTCs) represents an attractive feature of liquid biopsy that facilitates precision and tailored medicine in the management of metastatic castration-resistant prostate cancer (mCRPC). Prostein is an androgen-regulated transmembrane protein with high prostate specificity. Prostein-positive circulating tumor cell (CTC) was recently suggested to have diagnostic potential; however, no study has been conducted to evaluate its prognostic value in mCRPC. CTCs from mCRPC patients were enumerated using the CellSearch System. Prostein-positive CTCs were identified by immunostaining results. The relationships between prostein expression on CTCs and PSA response rate, PSA progression-free survival (PSA-PFS), radiographic progression-free survival (PFS), and overall survival (OS) were tested by Fisher's exact test or evaluated using Kaplan-Meier and multivariate Cox analyses. Prostein-positive CTCs were identified in 31 of 87 baseline samples from mCRPC patients and 16 of 51 samples collected at the first follow-up visit. PSA response rates were significantly lower in baseline prostein-positive patients (0%, 0/31) than in prostein-negative patients (19.6%, 11/56) (p = 0.007). The 31 prostein-positive patients had significantly shorter PSA-PFS (p < 0.001), radiographic PFS (p < 0.001), and OS (p = 0.018), compared to the 56 prostein-negative patients at baseline. The association with PSA-PFS maintained its significance (p = 0.028) in multivariate analyses. Analyzing prostein expression at the first follow-up as well as the conversion of prostein expression from baseline to follow-up samples not only confirmed the association with PSA-PFS, but also demonstrated prognostic significance with OS. Our study provides the first evidence to support the potential of prostein expression on CTCs to serve as a novel prognostic marker in mCRPC patients. Future large-scale prospective studies are needed to validate our findings.

Abstract B119: First-in-class orally active pharmacological inhibitors of TRPV6 for the treatment of advanced prostate cancer

Abstract The highly calcium selective ion channel TRPV6, has pronouced overexpression in many prostate cancers, is a promotor of prostate cancer growth and has been proposed as a prognostic marker in prostate cancer. A novel series of first-in-class TRPV6 inhibitors has been developed by the Queensland Emory Drug Discovery Initiative (QEDDI), a drug discovery and development group aiming to collaborativey translate academic biomedical research into new medicines. The preclinical lead drug candidate QED-203, is orally active and potently inhibits (low nM) calcium influx mediated by TRPV6 as assessed by both Ca2+ probe and electrophysiology assays, and TRPV6-driven NFAT activation as assessed by a luciferase reporter assay. Using RNAseq and qPCR analysis TRPV6 pharmacological inhibition and/or siRNA-mediated silencing was shown to remodel the expression of genes related to both NFAT and WNT signalling, as well as ER stress and the cell cycle. In prostate cancer cell lines that had increased levels of TRPV6, TRPV6 inhibition promoted cell cycle arrest, decreased proliferation and promoted apoptosis. Proliferation of enzalutamide resistant prostate cancer cell lines was also inhibited by QED-203. QED-203 exhibited greater potency over enzalutamide, darolutamide and apalutamide [androgen receptor targeting agents (ARTA)] in prostate cancer cell lines with clinically relevant AR mutations or those with the ARV7 splice variant. QED-203 appeared well suited to once-a-day oral dosing with a high bioavailability and an advantageous pharmacokinetic profile. In preclinical models, QED-203 was well tolerated in rodents and had similar in vivo efficacy to enzalutamide in a castrated LNCaP mouse model of prostate cancer as assessed by tumour growth and PSA levels. Increases in urine calcium levels and gene expression changes consistent with TRPV6 inhibition in isolated xenograft tumours, confirmed QED-203 TRPV6 target engagement in vivo. These studies suggest that the orally active TRPV6 inhibitor QED-203 represents a first-in-class mechanism to treat prostate cancer patients whose tumours have become resistant to current ARTA therapies. Pharmacological inhibitors of TRPV6, could be particularly valuable during the advanced stages of prostate cancer, where there is a clear unmet clinical need. Citation Format: Gregory Monteith, Kimberley Beaumont, Rebecca Pouwer, Rebecca Farrow, Matthew McLachlan, Mei Yeh, Therese Johnson, Raphael Rahmani, Claire Levrier, Hasanthi Wijesekera, Malika Kumarasiri, Grant Stuchbury, Terrie-Anne Cock, Andrew Harvey, Brian Dymock. First-in-class orally active pharmacological inhibitors of TRPV6 for the treatment of advanced prostate cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr B119.

Orexins and Prostate Cancer: State of the Art and Potential Experimental and Therapeutic Perspectives.

Prostate cancer (PCa) is the second most common cancer in humans. Peptides have recently been used as targeted therapeutics in cancers, due to their extensive multi-functional applications. Two hypothalamic peptides, orexins A (OXA) and B (OXB) and their specific receptors, orexin receptor 1 (OX1R) and 2 (OX2R), orchestrate several biological processes in the central nervous system and peripheral organs. However, in addition to their role in physiological responses, orexins are involved in numerous inflammatory and/or neoplastic pathologies. The presence and expression of orexins in different cancer models, including prostate cancer, and their role in inducing pro- or anti-apoptotic responses in tumor cell lines, suggest that the orexinergic system might have potential therapeutic action or function as a diagnostic marker in PCa. In addition to the traditional animal models for studying human PCa, the canine model might also serve as an additional tool, due to its clinical similarities with human prostate cancer.

Prostein expression in human tumors: A tissue microarray study on 19,202 tumors

Abstract Introduction/Objective Prostein (P501S), also termed solute carrier family 45 member 3 (SLC45A3) is an androgen regulated protein which is preferentially expressed in prostate epithelial cells. Because of its frequent expression in prostate cancer, prostein was suggested a diagnostic prostate cancer marker. Methods/Case Report In order to comprehensively assess the diagnostic utility of prostein immunohistochemistry, a tissue microarray containing 19,202 samples from 152 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. Results (if a Case Study enter NA) Prostein immunostaining was typically cytoplasmic, granular and perinuclear and predominated in prostate cancer. Prostein positivity was seen in 96.7% of 419 prostate cancers including 78.3% with a strong staining. In 12,233 extra-prostatic tumors, prostein positivity was observed in 9.8% of cases but only 0.4% had a strong staining. Extra-prostatic prostein positive tumors were 50 different tumor categories, 12 of which included at least one strongly positive case. Extra-prostatic tumors with highest rates of prostein positivity included salivary gland tumors (7.6%-44.4%), neuroendocrine neoplasms (15.8%-44.4%), adenocarcinomas of the gastrointestinal tract (7.3%-14.8%), biliopancreatic adenocarcinomas (3.6%-38.7%), hepatocellular carcinomas (8.1%), and adenocarcinomas of other organs (up to 21%). Conclusion In summary, our data provide a comprehensive overview on prostein expression in human cancers. Prostein is a highly sensitive prostate cancer marker occurring in &amp;gt;96% of prostate cancers. Because prostein can also be expressed in various other tumor entities, labeling of a tumor mass as a prostate cancer should not be based on prostein positivity alone.

Diagnostic role and prognostic impact of PSAP immunohistochemistry: A tissue microarray study on 31,358 cancer tissues from 127 different tumor types

Abstract Introduction/Objective Prostatic specific acid phosphatase (PSAP) protein is produced in prostate epithelial cells and it is used as an immunohistochemical marker for prostate cancer. However, studies have reported PSAP expression to occur in various other tumor entities as well. Methods/Case Report Prostatic specific acid phosphatase (PSAP) protein is produced in prostate epithelial cells and it is used as an immunohistochemical marker for prostate cancer. However, studies have reported PSAP expression to occur in various other tumor entities as well. Results (if a Case Study enter NA) In prostate cancer, PSAP staining was seen in 100% of Gleason 3 + 3, 95.5% Gleason 4 + 4, 93.8% recurrent prostate cancer under androgen deprivation therapy, 91.0% Gleason 5 + 5 and 31.2% small cell neuroendocrine prostate cancer. Reduced PSAP staining was strongly linked to high pT stage, high Gleason grade, lymph node metastasis, early PSA-recurrence (p&amp;lt;0.0001 each),high androgen receptor expression and TMPRSS2:ERG fusions. In multivariate analyses, low PSAP expression was able to predict PSA recurrence independent of pre- and postoperative prognostic markers in ERG negative cancers. In extra-prostatic cancers, PSAP immunostaining was only seen in 3 of 94 (3.2%) neuroendocrine tumors of the pancreas and in 1 of 129 (0.8%) diffuse type gastric adenocarcinomas. Conclusion A positive PSAP immunostaining is highly specific for prostate cancer and reduced PSAP expression is associated with an aggressive prostate cancer phenotype. The independent association of reduced PSAP expression with poor prognosis in ERG negative prostate cancer makes PSAP measurement a candidate marker for prognostic multiparameter panels for prostate cancer.

Crucial role of hsa-mir-503, hsa-mir-1247, and their validation in prostate cancer.

Prostate cancer (PC) is a common urinary system malignancy, and advanced PC patients had a poor prognosis due to recurrence or distant metastasis. Therefore, it's imperative to reveal more details in tumorigenesis and prognosis of PC patients. The miRNA and mRNA expression profile data of 485 PC patients were obtained from The Cancer Genome Atlas database. The univariate Cox regression was applied to screen miRNAs relating to prognosis of PC. Then miRTarBase was used to predict target mRNAs of miRNAs. The hsa-mir-503/hsa-mir-1247 knockdown in 22RV1 cells was established to evaluate the effect of these two miRNAs on tumor cell migration and invasion ability. Flow cytometry was used to detect the effect of hsa-mir-503/hsa-mir-1247 knockdown on 22RV1 apoptosis rate. Univariate Cox regression analysis identified hsa-mir-503 as a poor and hsa-mir-1247 as a favorable prognostic marker. Totally 649 target mRNAs were screened, among which DUSP19, FGF2, and SLC2A5 had a negative correlation with hsa-mir-503, while FGF2 and VSTM4 had a positive correlation with hsa-mir-1247. In 22RV1 cells, hsa-mir-503 was up-regulated, and hsa-mir-1247 was down-regulated. hsa-mir-503 knockdown attenuated the migration and invasion of 22RV1 cells, while hsa-mir-1247 knockdown exhibited the opposite effect. In addition, hsa-mir-503 knockdown promoted 22RV1 cell apoptosis. hsa-mir-1247 overexpression significantly inhibited the tumor growth of PC in vivo. Herein, we demonstrated that hsa-mir-503 and hsa-mir-1247 could serve as new prognostic markers of PC, and hsa-mir-1247 had great potential to inhibit PC progression by suppressing the migration and invasion ability in vitro and in vivo.

Diagnostic and Prognostic Value of miR-93 in Prostate Cancer: A Meta-Analysis and Bioinformatics Analysis.

Accurate and non-invasive diagnostic and prognostic markers are necessary to improve patient outcomes. MicroRNAs have been proposed as relatively non-invasive and pertinent biomarkers. miR-93 has been studied for its potential as a diagnostic and prognostic marker in prostate cancer (PCa), but findings from individual studies are inconsistent. We conducted a meta-analysis of its overall differential expression in 13 PCa studies and a bioinformatics analysis to provide a comprehensive appraisal of its diagnostic and prognostic role. We searched all published papers on miR-93 expression in PCa up to Nov 30, 2022 using PubMed, Science Direct, Web of Science, Cochrane Central Register of Controlled Trials databases. We used RevMan software to Meta-analyze the included literature. A bioinformatics analysis of genes and pathways that might be target to the effect of the mature miR-93-5p was carried out. The pooled standardized mean difference (SMD) of miR-93 expression in PCa, its area under the curve (AUC) and hazard ratio (HR) were 1.26, 95% CI [-0.34-2.86], 0.84, 95% CI [0.76 -0.93] and 1.67, 95% CI [0.98, 2.84] respectively. Bioinformatics analysis revealed that mature miR-93-5p may regulate genes such as SMAD1, SMAD7 and MAPK and the PI3K-Akt signaling pathways. miR-93 has significant diagnostic and prognostic value in PCa. These findings highlight the potential of miR-93 as a non-invasive biomarker for PCa and may contribute to earlier detection and prognostic assessment. The target genes and signaling pathways regulated by miR-93 may provide insights into the underlying molecular mechanisms of PCa.