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

2021 ◽  
Vol 22 (18) ◽  
pp. 10131
Author(s):  
Simita Gaglani ◽  
Edgar Gonzalez-Kozlova ◽  
Dara J. Lundon ◽  
Ashutosh K. Tewari ◽  
Navneet Dogra ◽  
...  

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.

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3373
Author(s):  
Milena Matuszczak ◽  
Jack A. Schalken ◽  
Maciej Salagierski

Prostate cancer (PCa) is the most common cancer in men worldwide. The current gold standard for diagnosing PCa relies on a transrectal ultrasound-guided systematic core needle biopsy indicated after detection changes in a digital rectal examination (DRE) and elevated prostate-specific antigen (PSA) level in the blood serum. PSA is a marker produced by prostate cells, not just cancer cells. Therefore, an elevated PSA level may be associated with other symptoms such as benign prostatic hyperplasia or inflammation of the prostate gland. Due to this marker’s low specificity, a common problem is overdiagnosis, which leads to unnecessary biopsies and overtreatment. This is associated with various treatment complications (such as bleeding or infection) and generates unnecessary costs. Therefore, there is no doubt that the improvement of the current procedure by applying effective, sensitive and specific markers is an urgent need. Several non-invasive, cost-effective, high-accuracy liquid biopsy diagnostic biomarkers such as Progensa PCA3, MyProstateScore ExoDx, SelectMDx, PHI, 4K, Stockholm3 and ConfirmMDx have been developed in recent years. This article compares current knowledge about them and their potential application in clinical practice.


2018 ◽  
Vol 46 (2) ◽  
pp. 532-545 ◽  
Author(s):  
Yu-Hui Wang ◽  
Jia Ji ◽  
Bi-Cheng Wang ◽  
Hao Chen ◽  
Zhong-Hua Yang ◽  
...  

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.


Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 81 ◽  
Author(s):  
Alexey S. Rzhevskiy ◽  
Sajad Razavi Bazaz ◽  
Lin Ding ◽  
Alina Kapitannikova ◽  
Nima Sayyadi ◽  
...  

During the last decade, isolation of circulating tumour cells via blood liquid biopsy of prostate cancer (PCa) has attracted significant attention as an alternative, or substitute, to conventional diagnostic tests. However, it was previously determined that localised forms of PCa shed a small number of cancer cells into the bloodstream, and a large volume of blood is required just for a single test, which is impractical. To address this issue, urine has been used as an alternative to blood for liquid biopsy as a truly non-invasive, patient-friendly test. To this end, we developed a spiral microfluidic chip capable of isolating PCa cells from the urine of PCa patients. Potential clinical utility of the chip was demonstrated using anti-Glypican-1 (GPC-1) antibody as a model of the primary antibody in immunofluorescent assay for identification and detection of the collected tumour cells. The microchannel device was first evaluated using DU-145 cells in a diluted Dulbecco’s phosphate-buffered saline sample, where it demonstrated >85 (±6) % efficiency. The microchannel proved to be functional in at least 79% of cases for capturing GPC1+ putative tumour cells from the urine of patients with localised PCa. More importantly, a correlation was found between the amount of the captured GPC1+ cells and crucial diagnostic and prognostic parameter of localised PCa—Gleason score. Thus, the technique demonstrated promise for further assessment of its diagnostic value in PCa detection, diagnosis, and prognosis.


2021 ◽  
Vol 8 (2) ◽  
pp. 107-113
Author(s):  
Aydemir Asdemir ◽  
Sevgi Durna Dastan ◽  
Esat Korgali ◽  
Tugba Yildiz Asdemir ◽  
Huseyin Saygin ◽  
...  

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.


2020 ◽  
Vol 20 (10) ◽  
pp. 847-854
Author(s):  
Ronald Bartzatt

Cancer of the prostate are cancers in which most incidences are slow-growing, and in the U.S., a record of 1.2 million new cases of prostate cancer occurred in 2018. The rates of this type of cancer have been increasing in developing nations. The risk factors for prostate cancer include age, family history, and obesity. It is believed that the rate of prostate cancer is correlated with the Western diet. Various advances in methods of radiotherapy have contributed to lowering morbidity. Therapy for hormone- refractory prostate cancer is making progress, for almost all men with metastases will proceed to hormone-refractory prostate cancer. Smoking cigarettes along with the presence of prostate cancer has been shown to cause a higher risk of mortality in prostate cancer. The serious outcome of incontinence and erectile dysfunction result from the cancer treatment of surgery and radiation, particularly for prostate- specific antigen detected cancers that will not cause morbidity or mortality. Families of patients, as well as patients, are profoundly affected following the diagnosis of prostate cancer. Poor communication between spouses during prostate cancer increases the risk for poor adjustment to prostate cancer. The use of serum prostate-specific antigen to screen for prostate cancer has led to a greater detection, in its early stage, of this cancer. Prostate cancer is the most common malignancy in American men, accounting for more than 29% of all diagnosed cancers and about 13% of all cancer deaths. A shortened course of hormonal therapy with docetaxel following radical prostatectomy (or radiation therapy) for high-risk prostate cancer has been shown to be both safe and feasible. Patients treated with docetaxel-estramustine had a prostate-specific antigen response decline of at least 50%. Cancer vaccines are an immune-based cancer treatment that may provide the promise of a non-toxic but efficacious therapeutic alternative for cancer patients. Further studies will elucidate improved methods of detection and treatment.


2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Xavier Ruiz-Plazas ◽  
Esther Rodríguez-Gallego ◽  
Marta Alves ◽  
Antonio Altuna-Coy ◽  
Javier Lozano-Bartolomé ◽  
...  

Abstract Background Conventional clinical biomarkers cannot accurately differentiate indolent from aggressive prostate cancer (PCa). We investigated the usefulness of a biomarker panel measured exclusively in biofluids for assessment of PCa aggressiveness. Methods We collected biofluid samples (plasma/serum/semen/post-prostatic massage urine) from 98 patients that had undergone radical prostatectomy. Clinical biochemistry was performed and several cytokines/chemokines including soluble(s) TWEAK, sFn14, sCD163, sCXCL5 and sCCL7 were quantified by ELISA in selected biofluids. Also, the expression of KLK2, KLK3, Fn14, CD163, CXCR2 and CCR3 was quantified by real-time PCR in semen cell sediment. Univariate, logistic regression, and receiver operating characteristic (ROC) analyses were used to assess the predictive ability of the selected biomarker panel in conjunction with clinical and metabolic variables for the evaluation of PCa aggressiveness. Results Total serum levels of prostate-specific antigen (PSA), semen levels of sTWEAK, fasting glycemia and mRNA levels of Fn14, KLK2, CXCR2 and CCR3 in semen cell sediment constituted a panel of markers that was significantly different between patients with less aggressive tumors [International Society of Urological Pathology (ISUP) grade I and II] and those with more aggressive tumors (ISUP grade III, IV and V). ROC curve analysis showed that this panel could be used to correctly classify tumor aggressiveness in 90.9% of patients. Area under the curve (AUC) analysis revealed that this combination was more accurate [AUC = 0.913 95% confidence interval (CI) 0.782–1] than a classical non-invasive selected clinical panel comprising age, tumor clinical stage (T-classification) and total serum PSA (AUC = 0.721 95% CI 0.613–0.830). Conclusions TWEAK/Fn14 axis in combination with a selected non-invasive biomarker panel, including conventional clinical biochemistry, can improve the predictive power of serum PSA levels and could be used to classify PCa aggressiveness.


2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 485-485 ◽  
Author(s):  
Wen-Sy Tsai ◽  
Drew Watson ◽  
Ying Chang ◽  
Ben Hsieh ◽  
Hung-Jen Shao ◽  
...  

485 Background: Up to 25% of patients with adenomas progress to having colorectal cancer. If detected early, adenomas can be removed with a diagnostic colonoscopy procedure, preventing cancer. Invasive colonoscopy is the only screening method with the sensitivity to accurately detect adenomas, but has a low compliance rate of 38% for screening. Available non-invasive tests (including stool-based multi-analyte tests) have very limited sensitivity for adenomas. Hence, there is an unmet need for a non-invasive test for adenoma detection. Methods: IRB-approved prospective study was conducted in 627 subjects 50 years or older- recommended for routine CRC screening- 405 subjects had adenoma or CRC, confirmed by colonoscopy with tumor biopsy. Two mL peripheral blood was processed using the CellMax biomimetic platform (CMx), which uses a microfluidic biochip to enumerate circulating tumor cells (CTCs). Nominal logistic regression was used to assess performance while proportional odds logistic regression and Cuzick’s trend test were used to determine association of CTC counts with cancer stage. Results: An increase in CTC count was significantly correlated with an increase in disease burden (Cuzick’s Test p-value < 0.0001). Furthermore, there was a significant association between CTC counts and stages of adenoma-carcinoma progression (Likelihood ratio p-value < 0.0001). The CTC enumeration was able to differentiate between healthy and diseased patients (adenoma + cancer). Conclusions: To the best of our knowledge, these are the first reported results for a blood test that has high accuracy for adenoma detection, and truly enables colorectal cancer prevention. This test can be administered in the primary care setting and drive high compliance.[Table: see text]


2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Changqing Yin ◽  
Changliang Luo ◽  
Wei Hu ◽  
Xu Ding ◽  
Chunhui Yuan ◽  
...  

As part of “liquid biopsy,” lots of literature indicated the potential diagnostic value of circulating cell-free DNA (cfDNA) in the management of prostate cancer (PCa). However, the literature on the accuracy of cfDNA detection in PCa has been inconsistent. Hence, we performed this meta-analysis to assess the diagnostic value of cfDNA in PCa. A total of 19 articles were included in this analysis according to the inclusion and exclusion criteria. We then investigated two main subgroups in this meta-analysis, including qualitative analysis of abnormal level of cfDNA and qualitative analysis of single-gene methylation alterations. Overall, the results of quantitative analysis showed sensitivity of 0.73 (95% CI, 0.62–0.82) and specificity of 0.80 (95% CI, 0.70–0.87), with an area under the curve (AUC) of 0.83 (95% CI, 0.80–0.86). For qualitative assessment, the values were 0.34 (95% CI, 0.22–0.48), 0.99 (95% CI, 0.97–1.00), and 0.91 (95% CI, 0.88–0.93), respectively. Our results suggest the pooled specificity of each subgroup is much higher than the specificity of prostate-specific antigen (PSA). However, they are not recommended for PCa screening alone, because their sensitivities are not higher than the conventional serum biomarkers PSA. We conclude that analysis of cfDNA can be used as an adjuvant tool for PCa screening.


2007 ◽  
Vol 25 (18) ◽  
pp. 2560-2566 ◽  
Author(s):  
David P. Smith ◽  
Rajah Supramaniam ◽  
Madeleine T. King ◽  
Jeanette Ward ◽  
Martin Berry ◽  
...  

Purpose It is important to meet the supportive care needs of cancer patients to ensure their satisfaction with their care. A population-wide sample of men younger than 70 years and newly diagnosed with prostate cancer was surveyed to determine their unmet needs in five domains and the factors predicting them. Patients and Methods Eligible men were younger than 70 years and residents in New South Wales, Australia, with newly diagnosed histopathologically confirmed prostate cancer. Sixty-seven percent of eligible men diagnosed between October 2000 and October 2001 participated. Demographic, treatment, and self-reported health data were collected. Information on cancer stage, grade, and prostate-specific antigen was obtained from medical records. Logistic regression analyses determined patient and treatment variables that predicted higher unmet needs. Results More than half (54%) of men with prostate cancer expressed some level of unmet psychological need, and 47% expressed unmet sexuality needs. Nearly one fourth expressed a moderate or high level of unmet need with respect to changes in sexuality. Sexuality needs were independently predicted by being younger, having had a secondary school education only, having had surgery, and being married, living as married, or divorced. Uncertainty about the future was also an important area of unmet need. Conclusion Attention should be given to sexual and psychological needs in the early months after diagnosis or treatment of prostate cancer, particularly in younger men, those with less education, and those having surgery. Research into better ways of meeting these needs will enable us to meet them with as much rigor as we meet clinical treatment needs.


Sign in / Sign up

Export Citation Format

Share Document