Diagnostic Biomarker For Prostate Cancer Research Articles

Evaluating Leukocyte Telomere Length and Myeloid-Derived Suppressor Cells as Biomarkers for Prostate Cancer.

Leukocyte telomere length (LTL) and myeloid-derived suppressor cells (MDSC) are associated with aging and the development and progression of cancer. However, the exact nature of this relationship remains unclear. Our study aimed to investigate the potential of LTL and MDSC as diagnostic biomarkers for prostate cancer while also seeking to deepen our understanding of the relationship of these potential biomarkers to each other. Our study involved patients undergoing a prostate biopsy. We analyzed the relative LTL in genomic DNA obtained from peripheral blood leukocytes as well as the percentage of MDSC and their subtypes in peripheral blood mononuclear cells (PBMC). Our evaluation focused on examining the relationship between LTL and MDSC and pathological diagnoses as well as investigating the correlation between LTL and MDSC levels. In our study of 102 participants, 56 were pathologically diagnosed with localized prostate cancer (cancer group), while 46 tested negative (control group). The cancer group exhibited significantly shorter LTL in comparison to the control group (p = 0.024). Additionally, the cancer group showed a tendency towards a higher percentage of monocytic MDSC (M-MDSC), although this difference did not reach statistical significance (p = 0.056). Our multivariate logistic regression analysis revealed that patients with shorter LTL and higher percentages of M-MDSC had a 2.98-fold (95% CI = 1.001-8.869, p = 0.049) and 3.03-fold (95% CI = 1.152-7.977, p = 0.025) increased risk of prostate cancer diagnosis, respectively. There was also a significant negative correlation between LTL and M-MDSC. (r = -0.347, p < 0.001). Our research has established a correlation between LTL and MDSC in patients undergoing biopsy for prostate cancer. Notably, we observed that individuals with localized prostate cancer tend to have shorter LTL and a higher percentage of M-MDSC prior to their diagnosis. These findings suggest that LTL and M-MDSC could potentially serve as adjunctive biomarkers for the early diagnosis of prostate cancer.

COL10A1 as a Prognostic Biomarker in Association with Immune Infiltration in Prostate Cancer.

The collagen type X alpha 1 (COL10A1) has recently been found to play an important role in the development and progression of cancer. However, the link between COL10A1 and the tumor immune microenvironment remains understood scantily. In the current study, the pan-cancer data of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were used to investigate the expression mode, the clinical prognostic and diagnostic value of COL10A1 in different tumors. We used TCGA data to assess the correlations between COL10A1 and clinical symptoms of prostate cancer. The R packages "edgR" and "clusterProfiler" were used for differential expression gene and enrichment analysis of COL10A1. Immunohistochemistry was further employed to corroborate the expression of COL10A1 gene in prostate cancer. After that, we used TIMER to evaluate the pertinence of COL10A1 expression to immune infiltration level in prostate cancer. On the whole, COL10A1 was expressed at significantly higher levels in a variety of tumor tissues than in the corresponding normal tissues. Besides, significant correlations with tumor prognosis and relative exactitude in predicting tumors show that COL10A1 may be a probable prognostic and diagnostic biomarker of prostate cancer. In addition, the evidence indicates a significant correlation between COL10A1 and clinical symptoms of prostate cancer. Furthermore, the main molecular functions of COL10A1 included humoral immune response, complement activation, immunoglobulin, regulation of complement activation, and regulation of humoral immune response. Finally, we found that COL10A1 expression is positively correlated with enhanced macrophage and M2 macrophage infiltration in prostate cancer. The study indicates that COL10A1 might participate in M2 macrophage polarization in prostate cancer. COL10A1 might be an innovative biomarker to evaluate tumor microenvironment immune cell infiltration and prognosis in prostate cancer.

Serum and Urinary Prostatic Cancer Antigen 3 as Diagnostic Biomarkers for Prostate Cancer

Serum and Urinary Prostatic Cancer Antigen 3 as Diagnostic Biomarkers for Prostate Cancer

Characterization of HOXB13 expression patterns in localized and metastatic castration-resistant prostate cancer.

HOXB13 is a key lineage homeobox transcription factor that plays a critical role in the differentiation of the prostate gland. Several studies have suggested that HOXB13 alterations may be involved in prostate cancer development and progression. Despite its potential biological relevance, little is known about the expression of HOXB13 across the disease spectrum of prostate cancer. To this end, we validated a HOXB13 antibody using genetic controls and investigated HOXB13 protein expression in murine and human developing prostates, localized prostate cancers, and metastatic castration-resistant prostate cancers. We observed that HOXB13 expression increases during later stages of murine prostate development. All localized prostate cancers showed HOXB13 protein expression. Interestingly, lower HOXB13 expression levels were observed in higher-grade tumors, although no significant association between HOXB13 expression and recurrence or disease-specific survival was found. In advanced metastatic prostate cancers, HOXB13 expression was retained in the majority of tumors. While we observed lower levels of HOXB13 protein and mRNA levels in tumors with evidence of lineage plasticity, 84% of androgen receptor-negative castration-resistant prostate cancers and neuroendocrine prostate cancers (NEPCs) retained detectable levels of HOXB13. Notably, the reduced expression observed in NEPCs was associated with a gain of HOXB13 gene body CpG methylation. In comparison to the commonly used prostate lineage marker NKX3.1, HOXB13 showed greater sensitivity in detecting advanced metastatic prostate cancers. Additionally, in a cohort of 837 patients, 383 with prostatic and 454 with non-prostatic tumors, we found that HOXB13 immunohistochemistry had a 97% sensitivity and 99% specificity for prostatic origin. Taken together, our studies provide valuable insight into the expression pattern of HOXB13 during prostate development and cancer progression. Furthermore, our findings support the utility of HOXB13 as a diagnostic biomarker for prostate cancer, particularly to confirm the prostatic origin of advanced metastatic castration-resistant tumors. © 2023 The Pathological Society of Great Britain and Ireland.

Label-free electrochemical immunosensor based on antibody-immobilized Fe-Cu layered double hydroxide nanosheetas an electrochemical probe for the detection of ultra trace amount of prostate cancer biomarker (PSA)

Here, a label-free immunosensor has been developed to detect prostate specific antigen as a diagnostic biomarker for prostate cancer. A pencil graphite electrode (PGE) coated with nanocomposites of iron-copper layered double hydroxide (Fe-Cu LDH) and reduced graphene oxide (rGO) was utilized as a sensor platform to capture the monoclonal anti-PSA antibody. The LDH/rGO nanocomposite can boost the electrical conductivity and enhance the surface area of the fabricated electrode; accordingly, it can efficiently amplify the electrode response and sensitivity in PSA detection. Electrochemical properties of the constructed sensor have been conducted utilizing cyclic voltammetry (CV), and electrochemical impedance spectroscopy(EIS). The PSA concentration level in serum samples was measured by monitoring the current changes of the Cu oxidation peak which was through the formation of antibody-PSA complexes on the surface of the electrode. The current response of the label-free immunosensor has been correlated to the concentration of PSA in a linear manner ranging from 100.0 fg/ml to 10.0 µg/ml with a limit of detection (LOD) of 63.24 fg/ml (S/N = 3). The morphology and structure of the synthesized Fe-Cu LDH/rGO nanocomposite was characterized using various analytical techniques such as field-emission scanning electron microscopy (FESEM), energy dispersive X-ray analysis (EDX), X-ray diffraction (XRD)and Fourier transform infrared (FTIR). The suggested immunosensor was employed to accurately and sensitively determine PSA concentration in serum samples with satisfactory results consistent with those achieved by enzyme-linked immunosorbent assay (ELISA) as a reference method. Finally, the obtained results indicate the promising application of the fabricated immunosensor in premature prostate cancer diagnostics.

The potential value of some adipokines and cytokines as diagnostic biomarkers for prostate cancer

Abstract Background: The role of Adipokines and proinflammatory cytokines is said to be crucial in the development of prostate cancer. Vaspin, Chemerin, Omentin, Interleukins IL-1β, interleukin-8 (IL8), Colony-stimulating factor (GM-CSF) and CC chemokine ligand 18 (CCL18) have all been proven to take part in tumor growth and progression. Aim of the study: The study aimed to explore circulating novel adipocytokines, such as serum of Vaspin, Chemerin and Omentin levels in patients with prostate cancer and to determine the level of selected proinflammatory cytokines (CCL18, IL-8, IL1, and GM-CSF). Methods: Three groups were included in the current study: Group (1) :32 patients with metastatic prostate cancer who received chemotherapy, Group (2): 30 untreated patients with nonmetastatic prostate cancer, and Group (3): 30 healthy controls. ELISA technique was used to assess serum levels of Vaspin, Chemerin, Omentin, CCL18, IL-8, IL1, and GM-CSF). Results: The Prostate cancer group exhibited higher serum levels of Vaspin, Chemerin, Omentin, CCL18, IL-8, IL1, and GM-CSF compared to the control group. Chemotherapy-treated patients exhibited significantly increased levels of the pro-inflammatory cytokines (IL-8) and Adipokines (Vaspin and Omentin) and decreased levels of the pro-inflammatory cytokines (IL-1) and Adipokines (Chemerin). The correlation analysis showed a significant positive correlation of serum Chemerin with Vaspin (r = 0.957, p-value&lt;0.0001), IL-8 (r = 0.9475, p-value &lt; 0.0001) and IL-1β (r = 0.7771, p-value &lt; 0.0029). Omentin and GS-CSF levels showed a non-significant positive correlation with Chemerin level (r = 0.1259; p = 0.6967).) and (r = 0.4247; p = 0.1688), respectively. While significant negative correlation was found between (Chemerin) with CCL-18 (r = –0.7916, p = 0.0022), serum Vaspin was significantly and negatively correlated with the levels of CCL-18 (r = –0.9349, p &lt; 0.0001), whereas there was a significant positive correlation between Vaspin level with IL-8 (R=0.9995, p &lt;0.0001); IL-1β(r = 0.561, p = 0.0057). The data demonstrated that Vaspin was positively and non-significantly correlated with the level of GS-CSF (r = 0.1437, p =0.656); serum Omentin was significantly and negatively correlated with the levels of GS-CSF (r = –0.8447, p = 0.0005), and CCL-18 (r= –0.7058, p = 0.0103), whereas there was a non-significant positive correlation between Omentin level with IL-8 (r = 0.4364, p = 0.1561). The data demonstrated that Omentin was negatively and non-significantly correlated with the level of IL-1β (r= –0.5366, p =0.0786). Conclusions: This study indicated increased levels of serum Vaspin, Chemerin, Omentin, Interleukins IL-1β, interleukin-8 (IL8), Colony-stimulating factor (GM-CSF) and CC chemokine ligand 18 (CCL18) in patients with Prostate cancer. These findings suggest that the cytokines, and adipokines, whose levels were elevated in the chemotherapy-treated patients may be involved in the pathophysiology of prostate cancer. Vaspin, Chemerin and Omentin might play an important role in Prostate cancer progression through their association with Adipokines and proinflammatory cytokines. More studies are needed to investigate the possible role of Vaspin, Chemerin and Omentin as potential markers in the development of Prostate cancer.

Tumor-derived extracellular vesicle nucleic acids as promising diagnostic biomarkers for prostate cancer.

Liquid biopsy as a non-invasive method has a bright future in cancer diagnosis. Tumor-related extracellular vesicles (EVs) and their components (nucleic acids, proteins, and lipids) in biofluids may exert multiple functions in tumor growth, metastasis, immune escape, and angiogenesis. Among all the components, nucleic acids have attracted the most interest due to their simplicity of extraction and detection. In this review, the biological functions of EVs in prostate cancer (PCa) genesis and progression were summarized. Moreover, the diagnostic value of EV RNA markers found in clinical body fluid samples was reviewed, including their trends, challenging isolation methods, and diagnostic efficacy. Lastly, because relatively much progress has been made in PCa, studies on EV DNA markers are also discussed.

PCA3 and TMPRSS2: ERG Urine Level as Diagnostic Biomarker of Prostate Cancer.

Prostate cancer is a highly prevalent urological carcinoma with an increasing incidence in Indonesia and all around the world. Early diagnosis can greatly affect treatment outcomes and increase life expectancy. Several biomarkers for detecting prostate cancer have been studied and showed great promise. This study aims to analyze prostate cancer antigen 3 (PCA3) as well as transmembrane serine protease 2:ERG (TMPRSS2:ERG) for diagnosing and serving as urine biomarkers in predicting prostate cancer incidences. We conducted an analytical study to assess the utility of PCA3 and TMPRSS2:ERG for detecting prostate cancer. Thirty samples were included in this study to see the utilization of PCA3 and TMPRSS2:ERG as diagnostic biomarkers of prostate cancer. A urine sample was taken and the PCA3 test was performed using the PCA3 PROGENSA test, while the TMPRSS2:ERG was performed using the chemiluminescent DNA probe method with a hybridization protection test. The average age of the subject was 61.07±8.3 years. Based on calculations using the Mann-Whitney test, there was a significant relationship between prostate-Specific Antigen (PSA) overexpression (p<0.001), TMPRSS2:ERG (p=0.001), and PCA3 (p=0.003) with prostate cancer incidence. The sensitivity of PCA3 and TMPRSS2:ERG in detecting prostate cancer was 76.9% and 92.3%, respectively. Hence, TMPRSS2:ERG and PCA3 can be used as biomarkers for the occurrence of prostate cancer. We also performed a Kruskal-Wallis test; however, there was no significant relationship between PSA (p=0.236), TMPRSS2:ERG (p=0.801), and PCA3 (p=0.091) with the Gleason score. There is a significant correlation between overexpression of PSA, TMPRSS2:ERG and PCA3 with the incidence of prostate cancer, and TMPRSS2:ERG and PCA3 can be used as biomarkers of prostate cancer.

Increased CD73 expression is associated with poorly differentiated Gleason score and tumor size in prostate cancer

There are few prostate cancer prognostic biomarkers. However, clinical difficulties in distinguishing between aggressive and non-aggressive tumors have been observed. CD73 is a 70-kDa glycosylphosphatidylinositol (GPI)-linked ecto-enzyme that reduces antitumor immunity in mouse models of tumor, particularly prostate cancer. It's believed to be a promising biomarker for predicting the clinical development and prognosis of certain tumor types. Its function in prostate cancer, however, is unknown. This study aims to investigate the hypothesis that CD73 may be used as a biomarker in prostate cancer diagnosis and/or prognosis. Nuclear and cytoplasmic CD73 staining has been evaluated by immunohistochemistry using benign (23) and malignant (75) prostate tissues. The immunohistochemical study showed nuclear and cytoplasmic CD73 staining in cancerous and non-cancerous prostate tissues. Increased CD73 staining was shown in prostate cancer tissues compared to benign prostate tissues. A negative association between CD73 expression and Gleason scores has been observed. However, increased cytoplasmic CD73 staining was significantly associated with increasing tumor size. This finding suggests that CD73 may have a role in cancer development or aggressiveness, indicating that more research is needed to better understand its function and determine whether it might be used as a diagnostic biomarker for prostate cancer.

LncRNA/miRNA/mRNA Network Introduces Novel Biomarkers in Prostate Cancer

The construction of a competing endogenous RNA (ceRNA) network is an important step in the identification of the role of differentially expressed genes in cancers. In the current research, we used a number of bioinformatics tools to construct the ceRNA network in prostate cancer and identify the importance of these modules in predicting the survival of patients with this type of cancer. An assessment of microarray data of prostate cancer and normal samples using the Limma package led to the identification of differential expressed (DE) RNAs that we stratified into mRNA, lncRNA, and miRNAs, resulting in 684 DEmRNAs, including 437 downregulated DEmRNAs (such as TGM4 and SCGB1A1) and 241 upregulated DEmRNAs (such as TDRD1 and CRISP3); 6 DElncRNAs, including 1 downregulated DElncRNA (H19) and 5 upregulated DElncRNAs (such as PCA3 and PCGEM1); and 59 DEmiRNAs, including 30 downregulated DEmiRNAs (such as hsa-miR-1274a and hsa-miR-1274b) and 29 upregulated DEmiRNAs (such as hsa-miR-1268 and hsa-miR-1207-5p). The ceRNA network contained a total of 5 miRNAs, 5 lncRNAs, and 17 mRNAs. We identified hsa-miR-17, hsa-miR-93, hsa-miR-150, hsa-miR-25, PART1, hsa-miR-125b, PCA3, H19, RND3, and ITGB8 as the 10 hub genes in the ceRNA network. According to the ROC analysis, the expression levels of 19 hub genes showed a high diagnostic value. Taken together, we introduce a number of novel promising diagnostic biomarkers for prostate cancer.

Urinary Zinc Loss Identifies Prostate Cancer Patients.

Prostate Cancer (PCa) is one of the most common malignancies in men worldwide, with 1.4 million diagnoses and 310,000 deaths in 2020. Currently, there is an intense debate regarding the serum prostatic specific antigen (PSA) test as a diagnostic tool in PCa due to the lack of specificity and high prevalence of over-diagnosis and over-treatments. One of the most consistent characteristics of PCa is the marked decrease in zinc; hence the lost ability to accumulate and secrete zinc represents a potential parameter for early detection of the disease. We quantified zinc levels in urine samples collected after a standardized prostatic massage from 633 male subjects that received an indication for prostate biopsy from 2015 and 2019 at AOU Città della Salute e della Scienza di Torino Hospital. We observed that the mean zinc levels were lower in the urine of cancer patients than in healthy subjects, with a decreasing trend in correlation with the progression of the disease. The combination of zinc with standard parameters, such as PSA, age, digital rectal exploration results, and magnetic resonance findings, displayed high diagnostic performance. These results suggest that urinary zinc may represent an early and non-invasive diagnostic biomarker for prostate cancer.

Urinary PCA3 a Superior Diagnostic Biomarker for Prostate Cancer among Ghanaian Men

Introduction Prostate cancer is one of the most commonly diagnosed cancers in men. Prostate-specific antigen (PSA) has been the biomarker of choice for screening and diagnosis of prostate cancer. However, inefficiencies exist with its diagnostic capabilities. This study thus evaluated the diagnostic and prognostic potential of urinary PCA3 as an alternative biomarker for prostate cancer in the Ghanaian population. Methods A hospital-based cross-sectional study was conducted at the Urology Department of the 37 Military Hospital, Accra, Ghana. A total of 237 participants aged 40 years and above with any form of suspected prostate disorder were recruited into the study after written informed consent was obtained. Total serum PSA levels was measured using the electrochemiluminescence method and transrectal ultrasound-guided systematic core needle biopsies were obtained from each study participant. Receiver operating characteristic curve (ROC) analysis was used to evaluate the diagnostic accuracies of serum PSA, DRE, and PCA3 as diagnostic tools for prostate cancer. These three diagnostic tools were also evaluated in various combinations to ascertain the combinations with the best diagnostic accuracy. Results Prostate cancer was diagnosed in 26.6% of the participants. Benign prostate hyperplasia and prostatitis were diagnosed in 48.5% and 24.9% participants, respectively. DRE had a sensitivity of 93.7% and a specificity of 12.1%. PSA had a sensitivity of 92.1% and a specificity of 16.1%. PCA3 had a sensitivity of 57.1% and a specificity of 85.6% and showed a better accuracy (AUC = 83.0) compared to PSA (AUC = 60.0) and DRE (AUC = 65.0) as individual diagnostic tools. The combination of DRE+PCA3 score had the best diagnostic accuracy (AUC = 0.80) with a sensitivity and specificity of 60.3% and 80.5%, respectively. Conclusion The urinary PCA3 assay showed a better diagnostic performance compared to serum PSA and DRE. PCA3 as a stand-alone and in combination with DRE could be a suitable complimentary marker in diagnosis and management of prostate cancer.

Glu-Urea-Lys Scaffold Functionalized Superparamagnetic Iron Oxide Nanoparticles Targeting PSMA for In Vivo Molecular MRI of Prostate Cancer.

The prostate specific membrane antigen (PSMA), extensively overexpressed on prostate cancer (PCa) cell surface, has been validated as a diagnostic biomarker for PCa. However, insufficient attention has been paid to the development of PSMA-specific probes loaded with small chemical molecules for the in vivo molecular imaging of PCa. In this study, we innovatively labelled superparamagnetic iron oxide nanoparticles with a PSMA-targeting Glu-Urea-Lys scaffold. An optimized synthetic route was developed to offer a physiochemically stable probe. The probe demonstrated high binding affinity (0.38 ± 0.08 μg(Fe)/mL) and binding specificity to PSMA expressed on prostate cancer cell surface in vitro. In a xenograft PCa mouse model, significant negative contrast of the implanted prostate cancer xenograft could be specifically observed by MRI 6 h after tail vein injection of the tracer (Fe, 20 mg/kg), exhibiting its potential to exclusively enhance magnetic resonance detection of PCa.

Proteomics reveals MRPL4 as a high-risk factor and a potential diagnostic biomarker for prostate cancer.

Through digital rectal examinations (DRE) and routine prostate-specific antigen (PSA) screening, early prostate cancer (PC) treatment has become possible. However, PC is a complex and heterogeneous disease. In vivo, cancer cells can invade adjacent tissues and metastasize to other tissues resulting in hard cures. Therefore, the key to improving PC patients' survival time is preventing cancer cells' metastasis. We used mass spectrometry to profile primary PC in patients with versus without metastatic PC. We named these two groups of PC patients as high-risk primary PC (n=11) and low-risk primary PC (n=7), respectively. At the same time, patients with benign prostatic hyperplasia (BPH, n=6) were used as controls to explore the possible factors driving PC metastasis. Based on comprehensive mass spectrometry analysis and biological validation, we found significant upregulation of MRPL4 expression in high-risk primary PC relative to low-risk primary PC and BPH. Further, through research of the extensive clinical cohort data in the database, we discovered that MRPL4 could be a high-risk factor for PC and serve as a potential diagnostic biomarker. The MRPL4 might be used as an auxiliary indicator for clinical status/stage of primary PC to predict patient survival time.

Discovering Gene Signature Shared by Prostate Cancer and Neurodegenerative Diseases Based on the Bioinformatics Approach.

Background Prostate cancer (PCa) is one of the highest frequent malignant tumors with very complicated pathogenesis. Genes of neurodegenerative diseases can influence tumor progression. But its role in the progression of PCa remains unclear. The purpose of the present academic work was to identify significant genes with poor outcome and their underlying mechanism. Methods The GSE70768, GSE88808, and GSE134051 datasets were downloaded to screen the differentially expressed genes (DEGs). The DEG screening criteria were as follows: P < 0.05 and differential fold change |logFC| ≥ 1. The common DEGs (co-DEGs) of the three datasets were obtained by the Robust Rank Aggregation (RRA) method. Gene Ontology (GO) function annotation and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis were performed using R software. Protein-protein interaction (PPI) network analysis was performed for co-DEGs using STRING to screen critical genes. Differential expression and prognosis of key genes were analyzed by the online tool Gene Expression Profiling Interactive Analysis 2 (GEPIA2). The intersection gene between key genes and neurodegenerative genes was identified by constructing a Venn diagram. Results A total of 263 co-DEGs were identified from the three datasets. GO analysis showed that co-DEGs were mainly involved in muscle contraction and blood circulation regulation. The top ten key genes were ACTG2, APOE, F5, CALD1, MYH11, MYL9, MYLK, TPM1, TPM2, and CALM1. GEPIA2 analysis showed that APOE, MYH11, and MYLK differ dramatically between tumor and normal tissues. These key genes are related to disease-free survival (DFS) in PCa. APOE was the intersection gene between key genes and Alzheimer-related genes. Conclusion The neurodegenerative gene APOE may be a potential prognostic and diagnostic biomarker for PCa.

Abstract 3383: Circular RNAs as non-invasive diagnostic biomarkers for prostate cancer

Abstract Prostate cancer is one of the most common cancers in men. The disease is largely indolent in nature and treatment of low-risk prostate cancer is not always necessary. However, a fraction of the patients will progress to aggressive disease which accounts for most of the cancer related mortality. Detection methods accurately differentiating between high- and low-risk patients for lethal prostate cancer is a critical need and currently, prostate biopsies and subsequent histopathology and molecular profiling are the most definitive way to differentiate between these two patient populations. But biopsies are invasive procedures associated with significant morbidity. Hence, there exists a critical need to develop non-invasive and highly sensitive diagnostic biomarkers to avoid unnecessary biopsies. Here, we propose to develop a novel biomarker panel which constitutes of a class of RNA molecules called circular RNA (circRNA) to be detected in liquid biopsies. Circular RNAs are covalently closed RNA structures, which are resistant to degradation by exoribonucleases because of the absence of free termini in their nucleotide chain. Due to their increased stability compared to their linear counterparts, circRNAs are ideal candidates for biomarkers, especially in non-invasive liquid biopsies. Using MiOncoCirc, a circRNA compendium from &amp;gt;2,000 primary and metastatic cancer tissues representing 40 cancer types, we first identified 9 circRNAs that are specifically expressed in prostate adenocarcinoma (PRAD) compared to all other cancer types. Next, we examined if these candidates are differentially expressed between PRAD and normal prostate tissues. Based on higher levels of expression which were statistically significant in the PRAD compared to normal prostate tissues, we promoted 4 circRNAs to our biomarker panel. In addition, our panel also includes 2 circRNAs that we predicted to arise from PRAD specific lncRNAs. To study the expression of the novel 6-circRNA biomarker expression in high-risk prostate cancer patients we developed a capture-based RNA sequencing assay. For the initial round we used this assay to test our pilot post-DRE patient urine sample EDRN cohort and detected expression of the prostate cancer-specific circRNAs in a subset of these post-DRE urine samples. We are in the process of expanding our test cohort which will also contain additional clinical annotations such as Gleason score. Post cohort assembly we intend to run our 6-circRNA capture assay on these samples to determine whether the expression levels of candidate circRNAs are correlated with disease stage and other clinical parameters. Our results will facilitate the rapid development of a diagnostic test using non-invasive urine samples for the early detection of high-risk prostate cancer. Citation Format: Palak Shah, Pushpinder Bawa, Lanbo Xiao, Yelena Kleyman, Josh Vo, Saravana M. Dhanasekaran, Jason Brown, Nicolette Loeding, Alexander Koons, Javed Siddiqui, Xuhong Cao, Arul M. Chinnaiyan. Circular RNAs as non-invasive diagnostic biomarkers for prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3383.

Urine Cell-Free MicroRNAs in Localized Prostate Cancer Patients.

Simple SummaryUrine cell-free microRNAs (cfmiRs) are promising biomarkers for the detection of prostate cancer (PCa) and may replace or complement prostate-specific antigen screening. This pilot study aims to demonstrate the diagnostic utility of urine cfmiRs for early-stage PCa using a robust microRNA (miR) panel based on next-generation sequencing. We assessed urine, plasma, and formalin-fixed paraffin-embedded tumor tissue samples obtained from patients diagnosed with pT2 PCa. Differentially expressed miRs were found in urine, plasma, and tumor samples obtained from PCa patients. Through bioinformatic analysis, several miRs were found as potential cfmiRs with utility for the detection of PCa. Our results showed that specific cfmiRs in urine samples from PCa patients may have potential utility in the detection of early-stage PCa.Prostate cancer (PCa) is the most common cancer in men. Prostate-specific antigen screening is recommended for the detection of PCa. However, its specificity is limited. Thus, there is a need to find more reliable biomarkers that allow non-invasive screening for early-stage PCa. This study aims to explore urine microRNAs (miRs) as diagnostic biomarkers for PCa. We assessed cell-free miR (cfmiR) profiles of urine and plasma samples from pre- and post-operative PCa patients (n = 11) and normal healthy donors (16 urine and 24 plasma) using HTG EdgeSeq miRNA Whole Transcriptome Assay based on next-generation sequencing. Furthermore, tumor-related miRs were detected in formalin-fixed paraffin-embedded tumor tissues obtained from patients with localized PCa. Specific cfmiRs signatures were found in urine samples of localized PCa patients using differential expression analysis. Forty-two cfmiRs that were detected were common to urine, plasma, and tumor samples. These urine cfmiRs may have potential utility in diagnosing early-stage PCa and complementing or improving currently available PCa screening assays. Future studies may validate the findings.

Long Noncoding RNA LAMTOR5-AS1 Interference Affects MicroRNA-506-3p/E2F6-Mediated Behavior of Non-Small Cell Lung Cancer Cells.

Long noncoding RNA LAMTOR5 antisense RNA 1 (LAMTOR5-AS1) has been certified as a risk predictor and diagnostic biomarker of prostate cancer. However, the expression and exact roles of LAMTOR5-AS1 in non-small cell lung cancer (NSCLC) remain unclear. Thus, we measured LAMTOR5-AS1 expression in NSCLC and gauged its clinical value. The detailed roles and downstream working mechanism of LAMTOR5-AS1 in NSCLC were comprehensively unraveled. qRT-PCR was applied to measure gene expression. Functionally, utilizing small interfering RNA, LAMTOR5-AS1 was ablated, and the functional alterations were addressed by means of different experiments. The targeting activities between LAMTOR5-AS1 and microRNA-506-3p (miR-506-3p) and between miR-506-3p and E2F transcription factor 6 (E2F6) were confirmed by RNA immunoprecipitation and luciferase reporter assays. LAMTOR5-AS1 overexpression in NSCLC was verified in TCGA datasets and our own cohort and manifested an evident relationship with poor prognosis. Interference with LAMTOR5-AS1 led to repression of the proliferation, cloning, and metastasis abilities of NSCLC cells in vitro. We further confirmed an obvious increase in LAMTOR5-AS1-silenced NSCLC cell apoptosis. Furthermore, the absence of LAMTOR5-AS1 restricted tumor growth in vivo. Mechanistically, LAMTOR5-AS1 sponged miR-506-3p in NSCLC cells. Furthermore, E2F6, a downstream target of miR-506-3p, was under the control of LAMTOR5-AS1, which was realized by decoying miR-506-3p. Rescue experiments showed that miR-506-3p suppression or E2F6 reintroduction was capable of remitting LAMTOR5-AS1 deficiency-triggered anticarcinogenic actions in NSCLC. Our study confirmed the exact roles of LAMTOR5-AS1 for the first time and revealed that LAMTOR5-AS1 knockdown disrupts the malignancy of NSCLC by targeting the miR-506-3p/E2F6 axis. Targeting the LAMTOR5-AS1/miR-506-3p/E2F6 pathway may be instrumental for managing patients with NSCLC.

Current biomarkers of prostate cancer

Prostate cancer is one of the most common malignancies in men. Early detection of prostate cancer is largely determined by the widely used prostate specific antigen (PSA) blood test. However, as a diagnostic and prognostic test of prostate cancer, PSA has limited specificity, sensitivity and leads to hyper or underdiagnosis, which, in turn, can lead to excessive treatment. There fore, it is very important to develop diagnostic markers that can be used to determine prostate cancer at an early stage of development, assess the possible progression of the disease and prescribe optimal therapy. Significant progress has been made in the discovery of biomarkers for prostate cancer. For example, biomarkers such as %-free PSA, Prostate Health Index (PHI) or 4K score can be used to increase specificity and reduce the number of unnecessary biopsies, while the PCA3 test can be used to reduce the number of repeated biopsies in men with previously negative biopsy. To determine aggressiveness and predict the outcome of the disease, tissue multigenic tests can be used, such as: T2-ERG, ExoDx, SelectMDx and ConfirmMDx, Prolaris, Oncoytype DX, Decipher. The development of such diagnostic tests opens up new opportunities for improving the diagnosis of prostate cancer, prognosis and decision-making on the appointment of therapy. And with the increase in their availability, finally, the possibility of an individual approach to the appointment of treatment for men with prostate cancer appears on the horizon. This review paper presents the data on the most advanced diagnostic biomarkers of prostate cancer.

A Homogeneous Label-Free Electrochemical microRNA Biosensor Coupling With G-Triplex/Methylene Blue Complex and λ-Exonuclease-Assisted Recycling Amplification.

A novel homogeneous label-free electrochemical biosensor using G-triplex/methylene blue (G3/MB) complex as the signal generator together with an amplification assisted by the λ-exonuclease (λ-Exo) has been successfully constructed for ultrasensitive microRNA (miRNA) detection. An integrated microelectrode was designed to realize the miniaturization of the homogeneous electrochemical assay. Taking advantage of G3, that can specifically bind with MB and decrease its diffusion current, a single-stranded functional DNA hairpin structure was designed as the bio-recognition probe. The probe consisted of G3, eight bases to block G3, and the complementary sequences of the target miRNA. Here we chose miRNA141—a potentially diagnostic biomarker of prostate cancer as the model target. The presence of miRNA141 could hybridize with the probe DNA to form a double-stranded structure with a 5′-phosphorylated terminus. Then λ-Exo was adopted to digest mononucleotides from the 5′-end, leading to the release of G3 part and miRNA141. The released miRNA could hybridize with another probe to trigger the cycling process, while the released G3 could therefore interact with MB to cause a detectable decrease of diffusion current. The proposed strategy showed a low detection limit of 16 fM and an excellent specificity to discriminate single-base mismatches. Furthermore, this sensor was applied to detect miRNA141 from diluted human serum samples, indicating that it has great potential in the application of nucleic acid detection in real samples.