Tumor-Derived Exosomal Long Noncoding RNAs as Promising Diagnostic Biomarkers for Prostate Cancer

Background/Aims: Exosomal circulating long non-coding RNAs (lncRNAs) in blood are emerging as clinically useful and non-invasive biomarkers for tumor diagnosis. However, normal cells can also secrete exosomes, so it is a prerequisite to obtain tumor-derived exosomes for better understanding of their diagnostic impacts in cancer. In this study, a dual-antibody-functionalized immunoaffinity system was established to isolate exosomes and investigate their lncRNAs expression pattern and clinical significance in prostate cancer (PCa). Methods: A commercially available kit was used to isolate total exosomes, which were then purified by a dual-antibody-functionalized immunoaffinity system. RT-qPCR was performed to detect the expression of exosomal lncRNAs. Receiver operating characteristic (ROC) curves were plotted to assess the diagnostic value. Results: Expression levels of two lncRNAs in tumor-derived exosomes were significantly higher than those in total exosomes. The levels of SAP30L-AS1 were upregulated in benign prostatic hyperplasia (BPH), and SChLAP1 levels were significantly higher in PCa than in BPH and healthy individuals. The area under the ROC curve indicated that SAP30L-AS1 and SChLAP1 had adequate diagnostic value to distinguish PCa from controls. Two lncRNAs separately combined with prostate specific antigen (PSA) possessed a moderate ability for discrimination. SAP30L-AS1 expression level was related to PSA values and tumor invasion. SChLAP1 expression was significantly higher in patients with higher Gleason scores, and was also effective in differentiating between BPH and PCa when the concentration of PSA was in the gray zone. Conclusion: The isolation of tumor-derived exosomes by dual-antibody-functionalized immunoaffinity systems and detection of their lncRNAs in plasma may lead to the identification of suitable biomarkers, with potential diagnostic utility.

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Prostate-Specific antigen value and micro RNAs as potential diagnostic biomarkers for prostate cancer

Medical Science and Discovery ◽

10.36472/msd.v8i2.479 ◽

2021 ◽

Vol 8 (2) ◽

pp. 107-113

Author(s):

Aydemir Asdemir ◽

Sevgi Durna Dastan ◽

Esat Korgali ◽

Tugba Yildiz Asdemir ◽

Huseyin Saygin ◽

...

Keyword(s):

Prostate Cancer ◽

Specific Antigen ◽

Diagnostic Value ◽

Micro Rna ◽

Control Group ◽

Diagnostic Biomarkers ◽

Expression Levels ◽

Non Invasive ◽

Cancer Group ◽

Micro Rnas

Objective: It is necessary to provide PSA alternatives or methods that can be used in conjunction with PSA to regress complications rising from negative biopsies and to increase diagnostic value. Patients and Methods: The study is consisting of 59 men as the sample group. Blood samples from the individuals are grouped as prostate cancer and BPH (benign prostatic hyperplasia) groups. 27 prostate cancer patients whom some of them also operated are assembled in the patients group and the other 32 individuals are grouped as BPH group. Micro RNA expression levels evaluated by RT-PCR. Results: Prostate cancer group when compared with the control group, it is observed that expression levels of miRNA-221 and miRNA-432 increased while expression levels of miRNA-17-5p, miRNA-30c, miRNA-107, miRNA-141, miRNA-145, miRNA-181a-2, miRNA-331-3p, miRNA-574-3p decreased and expression levels of miRNA-21 and miRNA-375 are quite similar between the groups. Conclusion: The prospect of strong and sensitive serum miRNA expression levels in prostate cancer cases which are easily detectable by non-invasive methods as biomarkers is a promising field of study. Nevertheless, it is currently necessary to work in conjunction with both tissue and serum to enhance both sensitivity and specificity of miRNAs as biomarkers. As such, expression levels of the same miRNAs in tissue and serum provide different expression values which in turn make it difficult to indicate a common biomarker.

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Three plasma-based microRNAs as potent diagnostic biomarkers for endometrial cancer

Cancer Biomarkers ◽

10.3233/cbm-200972 ◽

2021 ◽

pp. 1-12

Author(s):

Xingchen Fan ◽

Minmin Cao ◽

Cheng Liu ◽

Cheng Zhang ◽

Chunyu Li ◽

...

Keyword(s):

Endometrial Cancer ◽

Operating Characteristic ◽

Characteristic Curve ◽

External Validation ◽

Diagnostic Value ◽

Diagnostic Biomarkers ◽

Non Invasive ◽

Polymerase Chain ◽

Public Datasets ◽

Plasma Mirnas

BACKGROUND: MicroRNAs (miRNAs), with noticeable stability and unique expression pattern in plasma of patients with various diseases, are powerful non-invasive biomarkers for cancer detection including endometrial cancer (EC). OBJECTIVE: The objective of this study was to identify promising miRNA biomarkers in plasma to assist the clinical screening of EC. METHODS: A total of 93 EC and 79 normal control (NC) plasma samples were analyzed using Quantitative Real-time Polymerase Chain Reaction (qRT-PCR) in this four-stage experiment. The receiver operating characteristic curve (ROC) analysis was conducted to evaluate the diagnostic value. Additionally, the expression features of the identified miRNAs were further explored in tissues and plasma exosomes samples. RESULTS: The expression of miR-142-3p, miR-146a-5p, and miR-151a-5p was significantly overexpressed in the plasma of EC patients compared with NCs. Areas under the ROC curve of the 3-miRNA signature were 0.729, 0.751, and 0.789 for the training, testing, and external validation phases, respectively. The diagnostic performance of the identified signature proved to be stable in the three public datasets and superior to the other miRNA biomarkers in EC diagnosis. Moreover, the expression of miR-151a-5p was significantly elevated in EC plasma exosomes. CONCLUSIONS: A signature consisting of 3 plasma miRNAs was identified and showed potential for the non-invasive diagnosis of EC.

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Characterisation of the main PSA glycoforms in aggressive prostate cancer

Scientific Reports ◽

10.1038/s41598-020-75526-3 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Anna Gratacós-Mulleras ◽

Adrià Duran ◽

Akram Asadi Shehni ◽

Montserrat Ferrer-Batallé ◽

Manel Ramírez ◽

...

Keyword(s):

Prostate Cancer ◽

Blood Serum ◽

Specific Antigen ◽

Serum Levels ◽

Neoplastic Progression ◽

Healthy Individuals ◽

Hydrophilic Interaction ◽

Glycosylation Pattern ◽

Non Invasive ◽

Benign Prostate

Abstract Serum levels of prostate specific antigen (PSA) are commonly used for prostate cancer (PCa) detection. However, their lack of specificity to distinguish benign prostate pathologies from PCa, or indolent from aggressive PCa have prompted the study of new non-invasive PCa biomarkers. Aberrant glycosylation is involved in neoplastic progression and specific changes in PSA glycosylation pattern, as the reduction in the percentage of α2,6-sialic acid (SA) are associated with PCa aggressiveness. In this study, we have characterised the main sialylated PSA glycoforms from blood serum of aggressive PCa patients and have compared with those of standard PSA from healthy individuals’ seminal plasma. PSA was immunoprecipitated and α2,6-SA were separated from α2,3-SA glycoforms using SNA affinity chromatography. PSA N-glycans were released, labelled and analysed by hydrophilic interaction liquid chromatography combined with exoglycosidase digestions. The results showed that blood serum PSA sialylated glycoforms containing GalNAc residues were largely increased in aggressive PCa patients, whereas the disialylated core fucosylated biantennary structures with α2,6-SA, which are the major PSA glycoforms in standard PSA from healthy individuals, were markedly reduced in aggressive PCa. The identification of these main PSA glycoforms altered in aggressive PCa opens the way to design specific strategies to target them, which will be useful to improve PCa risk stratification.

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The diagnostic value of a new formula combining age and prostate volume in prostate cancer

10.31083/jomh.2021.080 ◽

2021 ◽

Keyword(s):

Prostate Cancer ◽

Linear Model ◽

Prostate Volume ◽

Specific Antigen ◽

Transrectal Ultrasound ◽

High Sensitivity ◽

Roc Curves ◽

Diagnostic Value ◽

Number Of Patients ◽

Log Linear

Background and objective: This study combined two clinical indicators (age and prostate volume (PV)) to generate age to PV (AVR) ratio, whose diagnostic value for prostate cancer (PCa) was examined based on prostate speciﬁc antigen (PSA) in the range of 4--20.0 ng/mL. Methods: The medical records of patients who underwent transrectal ultrasound-guided biopsy of the prostate in our hospital from June 2015 to June 2019 were examined retrospectively. According to the pathological results of the biopsy, the patients were divided into the PCa and benign prostatic hyperplasia (BPH) groups. Receiver operating characteristic (ROC) curves for TPSA, PSAD, PV, (F/T)PSA, AVR, and PSA-AV were plotted with SPSS 26.0 and GraphPad Prism 5.0, and areas under the ROC curves (AUROCs) were determined and compared by Delong test. A log-linear model was used to compare AVR and other parameters with similar high sensitivities, for speciﬁcity. Results: The AUROC for AVR was signiﬁcantly different from those of TPSA (p < 0.001), PV (p = 0.004),(F/T)PSA (p < 0.001), and PSA-AV (p = 0.006), and similar to that of PSAD (p = 0.064). With the same high sensitivity (90.0%), log-linear model analysis showed that the speciﬁcity of AVR was signiﬁcantly higher than those of TPSA and (F/T)PSA (p < 0.01), while there were no signiﬁcant differences among AVR and PSAD, PV and PSA-AV. Conclusion: With PSA in the range of 4--20.0 ng/mL, AVR may be useful in sparing an invasive intervention for a number of patients.

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MiR-378 Has the Capacity to Serve as a Diagnostic Biomarker for Prostate Cancer Patient

10.21203/rs.3.rs-53222/v1 ◽

2020 ◽

Author(s):

Shuangqing Cao ◽

Lei Zheng

Keyword(s):

Prostate Cancer ◽

Roc Curve ◽

Roc Analysis ◽

Operating Characteristic ◽

Diagnostic Value ◽

Healthy Individuals ◽

Chi Square ◽

Urine Retention ◽

Potential Biomarker ◽

Chi Square Test

Abstract Background: This study aimed to examine the expression of serum miR-378 in prostate cancer (PCa) patients and healthy individuals and to identify the value of miR-378 in PCa diagnosis.Methods: The expression of serum miR-378 between groups was compared by t-test. The association between miR-378 expression and clinical characteristics of PCa patients was assessed using Chi-square test. The diagnostic value of serum miR-378 in PCa was estimated by the receiver operating characteristic (ROC) analysis.Results: The expression level of serum miR-378 in PCa patients was significantly lower than that in healthy individuals (P<0.0001). MiR-378 expression was affected by positive AR (P=0.004), large Gleason score (P=0.013) and advanced TNM stage (P=0.020), however, it had no relationship with age, serum PSA, NED rate and urine retention (all, P>0.05). The ROC curve showed that the optimal cutoff value was 1.845, giving the sensitivity and specificity of 75.21% and 89.77%, respectively. Besides, the area under the ROC curve (AUC) was 0.894, indicating serum miR-378 was of great diagnostic value in screening PCa patients from healthy controls (P<0.0001, 95%CI =0.852-0.936).Conclusions: Taken together, the increased expression of serum miR-378 might act as a potential biomarker for PCa diagnosis.

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Evaluation of MicroRNAs as Non-Invasive Diagnostic Markers in Urinary Cells from Patients with Suspected Prostate Cancer

Diagnostics ◽

10.3390/diagnostics10080578 ◽

2020 ◽

Vol 10 (8) ◽

pp. 578

Author(s):

Angelika Borkowetz ◽

Andrea Lohse-Fischer ◽

Jana Scholze ◽

Ulrike Lotzkat ◽

Christian Thomas ◽

...

Keyword(s):

Prostate Cancer ◽

Molecular Markers ◽

Diagnostic Performance ◽

Operating Characteristic ◽

Clinical Performance ◽

Diagnostic Value ◽

Non Invasive ◽

Diagnostic Potential ◽

Specificity And Sensitivity ◽

Diagnostic Power

Currently used tumor markers for early diagnosis of prostate cancer (PCa) are often lacking sufficient specificity and sensitivity. Therefore, the diagnostic potential of selected microRNAs in comparison to serum PSA levels and PSA density (PSAD) was explored. A panel of 12 PCa-associated microRNAs was quantified by qPCR in urinary sediments from 50 patients with suspected PCa undergoing prostate biopsy, whereupon PCa was detected in 26 patients. Receiver operating characteristic (ROC) curve analyses revealed a potential for non-invasive urine-based PCa detection for miR-16 (AUC = 0.744, p = 0.012; accuracy = 76%) and miR-195 (AUC = 0.729, p = 0.017; accuracy = 70%). While serum PSA showed an insufficient diagnostic value (AUC = 0.564, p = 0.656; accuracy = 50%) in the present cohort, PSAD displayed an adequate diagnostic performance (AUC = 0.708, p = 0.031; accuracy = 70%). Noteworthy, the combination of PSAD with the best candidates miR-16 and miR-195 either individually or simultaneously improved the diagnostic power (AUC = 0.801–0.849, p < 0.05; accuracy = 76–90%). In the sub-group of patients with PSA ≤ 10 ng/mL (n = 34), an inadequate diagnostic power of PSAD alone (AUC = 0.595, p = 0.524; accuracy = 68%) was markedly surpassed by miR-16 and miR-195 individually as well as by their combination with PSAD (AUC = 0.772–0.882, p < 0.05; accuracy = 74–85%). These findings further highlight the potential of urinary microRNAs as molecular markers with high clinical performance. Overall, these results need to be validated in a larger patient cohort.

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MiR-93/miR-375: Diagnostic Potential, Aggressiveness Correlation and Common Target Genes in Prostate Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms21165667 ◽

2020 ◽

Vol 21 (16) ◽

pp. 5667

Author(s):

Ewa Ciszkowicz ◽

Paweł Porzycki ◽

Małgorzata Semik ◽

Ewa Kaznowska ◽

Mirosław Tyrka

Keyword(s):

Prostate Cancer ◽

Operating Characteristic ◽

Target Genes ◽

Diagnostic Value ◽

Tissue Samples ◽

Non Invasive ◽

Diagnostic Potential ◽

Diagnostic Applications ◽

First Time ◽

Common Target

Dysregulation of miRNAs has a fundamental role in the initiation, development and progression of prostate cancer (PCa). The potential of miRNA in gene therapy and diagnostic applications is well documented. To further improve miRNAs’ ability to distinguish between PCa and benign prostatic hyperplasia (BPH) patients, nine miRNA (-21, -27b, -93, -141, -205, -221, -182, -375 and let-7a) with the highest reported differentiation power were chosen and for the first time used in comparative studies of serum and prostate tissue samples. Spearman correlations and response operating characteristic (ROC) analyses were applied to assess the capability of the miRNAs present in serum to discriminate between PCa and BPH patients. The present study clearly demonstrates that miR-93 and miR-375 could be taken into consideration as single blood-based non-invasive molecules to distinguish PCa from BPH patients. We indicate that these two miRNAs have six common, PCa-related, target genes (CCND2, MAP3K2, MXI1, PAFAH1B1, YOD1, ZFYVE26) that share the molecular function of protein binding (GO:0005515 term). A high diagnostic value of the new serum derived miR-182 (AUC = 0.881, 95% confidence interval, CI = 0.816–0.946, p < 0.0001, sensitivity and specificity were 85% and 79%, respectively) is also described.

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HULC and Linc00152 Act as Novel Biomarkers in Predicting Diagnosis of Hepatocellular Carcinoma

Cellular Physiology and Biochemistry ◽

10.1159/000430387 ◽

2015 ◽

Vol 37 (2) ◽

pp. 687-696 ◽

Cited By ~ 105

Author(s):

Jun Li ◽

Xiaochen Wang ◽

Junwei Tang ◽

Runqiu Jiang ◽

Wenjie Zhang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Operating Characteristic ◽

Roc Curves ◽

Diagnostic Value ◽

Double Blind ◽

Novel Biomarkers ◽

Non Coding Rnas ◽

Validation Set ◽

And Control ◽

Tissues Expression

Background/Aims: The alterations of long non-coding RNAs (lncRNAs) are related to multiple diseases. They can be detected in plasma as biomarkers for the diagnosis of multiple diseases. In this study, we aimed to determine the expression of circulating lncRNAs in human, which may be promising biomarkers for the diagnosis of hepatocellular carcinoma (HCC). Methods: Eight lncRNAs were chosen as candidates on the basis of the literature to evaluate the diagnostic value and accuracy of the plasma lncRNA profiling system. The candidate lncRNAs were validated by qRT-PCR arranged in the training and validation sets. Additional double-blind testing was performed in 20 patients clinically suspected of having HCC. Results: Circulating HULC and Linc00152 were significantly up-regulated in plasma samples of HCC patients during training set and validation set. Areas under the receiver operating characteristic (ROC) curves of the validated two lncRNAs signature were 0.78 and 0.85, respectively. Combination of HULC and Linc00152 possessed a moderate ability to discrimination between HCC and control with an area under ROC value of 0.87 while the combination of AFP was 0.89 with a positive correlation with tissues expression. Conclusions: Our results suggest that both plasma levels of HULC and Linc00152 achieve a fine diagnostic accuracy in diagnosing ontogenesis and metastasis of HCC and may act as novel biomarkers for HCC.

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Exosomes as A Next-Generation Diagnostic and Therapeutic Tool in Prostate Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms221810131 ◽

2021 ◽

Vol 22 (18) ◽

pp. 10131

Author(s):

Simita Gaglani ◽

Edgar Gonzalez-Kozlova ◽

Dara J. Lundon ◽

Ashutosh K. Tewari ◽

Navneet Dogra ◽

...

Keyword(s):

Prostate Cancer ◽

Liquid Biopsy ◽

Specific Antigen ◽

Unmet Need ◽

Diagnostic Value ◽

Advanced Technology ◽

Detection Methods ◽

Current Application ◽

Non Invasive ◽

Therapeutic Value

Extracellular vesicles (EVs) have brought great momentum to the non-invasive liquid biopsy procedure for the detection, characterization, and monitoring of cancer. Despite the common use of PSA (prostate-specific antigen) as a biomarker for prostate cancer, there is an unmet need for a more specific diagnostic tool to detect tumor progression and recurrence. Exosomes, which are EVs that are released from all cells, play a large role in physiology and pathology, including cancer. They are involved in intercellular communication, immune function, and they are present in every bodily fluid studied—making them an excellent window into how cells are operating. With liquid biopsy, EVs can be isolated and analyzed, enabling an insight into a potential therapeutic value, serving as a vehicle for drugs or nucleic acids that have anti-neoplastic effects. The current application of advanced technology also points to higher-sensitivity detection methods that are minimally invasive. In this review, we discuss the current understanding of the significance of exosomes in prostate cancer and the potential diagnostic value of these EVs in disease progression.

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MicroRNA-940 as a Potential Serum Biomarker for Prostate Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.628094 ◽

2021 ◽

Vol 11 ◽

Author(s):

Smrithi Rajendiran ◽

Sayantan Maji ◽

Ahmed Haddad ◽

Yair Lotan ◽

Rajesh R. Nandy ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Progression ◽

Characteristic Curve ◽

Specific Antigen ◽

Cancer Prognosis ◽

High Survival ◽

Non Invasive ◽

Non Coding Rnas ◽

Clinically Significant ◽

Culture Supernatants

Prostate cancer is one of the leading causes of death despite an astoundingly high survival rate for localized tumors. Though prostate specific antigen (PSA) test, performed in conjunction with digital rectal examinations, is reasonably accurate, there are major caveats requiring a thorough assessment of risks and benefits prior to conducting the test. MicroRNAs, a class of small non-coding RNAs, are stable molecules that can be detected in circulation by non-invasive methods and have gained importance in cancer prognosis and diagnosis in the recent years. Here, we investigate circulating miR-940, a miRNA known to play a role in prostate cancer progression, in both cell culture supernatants as well as patient serum and urine samples to determine the utility of miR-940 as a new molecular marker for prostate cancer detection. We found that miR-940 was significantly higher in serum from cancer patients, specifically those with clinically significant tumors (GS ≥ 7). Analysis of receiver operating characteristic curve demonstrated that miR-940 in combination with PSA had a higher area under curve value (AUC: 0.818) than the miR-940 alone (AUC: 0.75) for the diagnosis of prostate cancer. This study provides promising results suggesting the use of miR-940 for prostate cancer diagnosis.

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