Circulating mRNAs and miRNAs as candidate markers for the diagnosis and prognosis of prostate cancer (original) (raw)
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Circulating microRNA signature for the diagnosis of very high-risk prostate cancer
Proceedings of the National Academy of Sciences of the United States of America, 2016
We report the identification of a molecular signature using the Scano-miR profiling platform based on the differential expression of circulating microRNAs (miRNA, miR) in serum samples specific to patients with very high-risk (VHR) prostate cancer (PCa). Five miRNA PCa biomarkers (miR-200c, miR-605, miR-135a*, miR-433, and miR-106a) were identified as useful for differentiating indolent and aggressive forms of PCa. All patients with VHR PCa in the study had elevated serum levels of miR-200c. Circulating miR-433, which was differentially expressed in patients with VHR versus low-risk (LR) forms of PCa, was not detectable by quantitative real-time PCR in samples from healthy volunteers. In blind studies, the five miRNA PCa biomarkers were able to differentiate patients with VHR PCas from those with LR forms as well as healthy individuals with at least 89% accuracy. Biological pathway analysis showed the predictive capability of these miRNA biomarkers for the diagnosis and prognosis of...
A Circulating MicroRNA Signature as a Biomarker for Prostate Cancer in a High Risk Group
Journal of Clinical Medicine, 2015
Introduction: Mi(cro)RNAs are small non-coding RNAs whose differential expression in tissue has been implicated in the development and progression of many malignancies, including prostate cancer. The discovery of miRNAs in the blood of patients with a variety of malignancies makes them an ideal, novel biomarker for prostate cancer diagnosis. The aim of this study was to identify a unique expression profile of circulating miRNAs in patients with prostate cancer attending a rapid access prostate assessment clinic. Methods: To conduct this study blood and tissue samples were collected from 102 patients (75 with biopsy confirmed cancer and 27 benign samples) following ethical approval and informed consent. These patients were attending a prostate assessment clinic. Samples were reverse-transcribed using stem-loop primers and expression levels of each of 12 candidate miRNAs were determined using real-time quantitative polymerase chain reaction. miRNA expression levels were then correlated with clinicopathological data and subsequently analysed using qBasePlus software and Minitab. Results: Circulating miRNAs were detected and quantified in all subjects. The analysis of miRNA mean expression levels revealed that four miRNAs were significantly dysregulated, including let-7a (p = 0.005) which has known tumour suppressor characteristics, along with miR-141
The utility of urine-circulating miRNAs for detection of prostate cancer
British Journal of Cancer, 2016
Background: In this paper, the utility of urine-circulating microRNAs (miRNAs) as the potential biomarker of prostate cancer (PCa), the second most prevalent male cancer worldwide, was evaluated. Methods: Cancerous (N ¼ 56) and non-cancerous (N ¼ 16) prostate tissues were analysed on TaqMan Low Density Array, with the initial screening of 754 miRNAs in a subset of the samples. The abundance of selected miRNAs was analysed in urine specimens from two independent cohorts of patients with PCa (N ¼ 215 overall), benign prostatic hyperplasia (BPH; N ¼ 23), and asymptomatic controls (ASC; N ¼ 62) by means of quantitative reverse transcription PCR. Results: Over 100 miRNAs were found deregulated in PCa as compared with non-cancerous prostate tissue. After thorough validation, four miRNAs were selected for the analysis in urine specimens. The abundance of miR-148a and miR-375 in urine was identified as specific biomarkers of PCa in both cohorts. Combined analysis of urine-circulating miR-148a and miR-375 was highly sensitive and specific for PCa in both cohorts (AUC ¼ 0.79 and 0.84) and strongly improved the diagnostic power of the PSA test (AUC ¼ 0.85, cohort PCa1), including the grey diagnostic zone (AUC ¼ 0.90). Conclusions: Quantitative measurement of urine-circulating miR-148a and miR-375 can serve as the non-invasive tool for sensitive and specific detection of PCa.
International Urology and Nephrology
Purpose Prostate cancer (PCa) is a common tumor disease in western countries and a leading cause of cancer-driven mortality in men. Current methods for prostate cancer detection, like prostate-specific antigen screening, lead to significant overtreatment. The purpose of the study was to analyze circulating microRNAs in serum as non-invasive biomarkers in patients with diagnosis of prostate cancer and healthy individuals. Methods This preliminary study included a population of 20 patients with mean age of 68.6 years and mean PSA of 21.3 ng/ ml. Eight healthy patients were used as control. MiRNAs were quantified in the total RNA fraction extracted from serum and levels of five microRNAs (miR-106b, miR-141, miR-21, mir-34a, and miR-375) were quantified by RT-qPCR. Statistical analyses evaluated correlation between clinicopathological data and miRNAs expression levels. Results Relative expression ratios of miR-106b, miR-141-3p, miR-21, and miR-375 were significantly increased (1.8-, 1.9-, 2.4-, and 2.6-fold, respectively) in the PCa group compared to healthy control. Using receiver operating characteristics, the highest area under the curve equal to 0.906 was obtained for miR-357 and indicates a very good diagnostic properties of this biomarker. We found expression level of mir-34a not related with PCa. Conclusions Our results support previous findings on the possibility of discriminating prostate cancer patients from healthy controls by detecting miRNA (miR-141-3p, miR-21, and miR-375). Further insights into miRNA abundance and characteristics are necessary to validate the panel of miRNA as surrogate markers in diagnosis of prostate cancer.
Turkish Journal of Medical Sciences, 2021
Background/aim: MicroRNAs (miRNAs) are known up-to-date candidate biomarkers for several diseases. In addition, obtaining miRNA from different body fluids such as serum, plasma, saliva, and urine is relatively easy to handle. Herein we aimed to detect miRNAs as biomarkers for early stage prostate cancer (PC). For this purpose, we used urine and serum samples to detect any significant differences in miRNA profiles between patients and healthy controls. Materials and methods: Total ribonucleic acid (RNA) in urine and serum samples were isolated from eight untreated PC patients, thirty healthy individuals were screened for miRNA profile, and candidate miRNAs were validated. Whole urinary and serum miRNA profile was analyzed using Affymetrix GeneChip miRNA 4.0 Arrays. Candidate miRNAs were investigated by stem-loop reverse transcriptionpolymerase chain reaction. Results: When we analyzed the urinary samples of PC patients, 49 miRNAs were detected to be upregulated and 14 miRNAs were found to be downregulated when compared with healthy controls. According to the serum samples, 19 miRNAs were found to be upregulated, and 21 miRNAs were found to be downregulated when compared with healthy individuals as well. Interestingly, we detected only four overlapping miRNAs (MIR320A, MIR4535, MIR4706, MIR6750) that commonly increase or decrease in both serum and urine samples. Among them, MIR320A was found to be downregulated, and MIR4535, MIR4706, and MIR6750 were found to be upregulated for urine samples. However, only MIR6750 was upregulated and the other three miRNAs were downregulated for serum samples. Conclusion: Notably, the expression profile of MIR320A was significantly altered in urine specimens of prostate cancer patients. We considered that MIR320A has been evaluated as a valuable biomarker that can be used in the early diagnosis of PC.
Circulating microRNAs as potential new biomarkers for prostate cancer
British journal of cancer, 2013
Since they were first described in the 1990s, circulating microRNAs (miRNAs) have provided an active and rapidly evolving area of current research that has the potential to transform cancer diagnostics and therapeutics. In particular, miRNAs could provide potential new biomarkers for prostate cancer, the most common cause of cancer in UK men. Current diagnostic tests for prostate cancer have low specificity and poor sensitivity. Further, although many prostate cancers are so slow growing as not to pose a major risk to health, there is currently no test to distinguish between these and cancers that will become aggressive and life threatening. Circulating miRNAs are highly stable and are both detectable and quantifiable in a range of accessible bio fluids, thus have the potential to be useful diagnostic, prognostic and predictive biomarkers. This review aims to summarise the current understanding of circulating miRNAs in prostate cancer patients and their potential role as biomarkers.
The Potential Prognostic and Diagnostic Role of MiRNAs as Novel Biomarkers for Prostate Cancer
2019
Prostate cancer (PC) is considered the second most commonly diagnosed malignancy, and the fifth leading cause of cancer related deaths in males worldwide. It is associated with a variety of risk factors as age, family history, race, hormonal change and genetic abnormalities [1,2]. An important prognostic indicator of prostate cancer is the histopathologic grading (Gleason score). Gleason-based grading allows classifying tumors according to their relative degree of differentiation by assigning a score from 1 (most differentiated) to 5 (least differentiated). However, it has been elucidated that tumors with similar histological patterns may provide different clinical outcomes, so Gleason score cannot exactly predict the aggressiveness of the disease although it is a powerful prognostic indicator [3]. prostate-specific antigen (PSA), which is the most widely used biomarker for diagnosis of PC, though it has a low specificity [4]. also, using this marker for screening the population lea...
Large-scale Circulating microRNA Profiling for the Liquid Biopsy of Prostate Cancer
Clinical Cancer Research, 2019
Purpose: The high false-positive rate of prostate-specific antigen (PSA) may lead to unnecessary prostate biopsies. Therefore, the United States Preventive Services Task Force recommends that decisions regarding PSA-based screening of prostate cancer should be made with caution in men ages 55–69 years, and that men ≥70 years should not undergo PSA screening. Here, we investigated the potential of serum miRNAs as an accurate diagnostic method in patients with suspected prostate cancer. Experimental Design: Serum samples of 809 patients with prostate cancer, 241 negative prostate biopsies, and 500 patients with other cancer types were obtained from the National Cancer Center, Japan. Forty-one healthy control samples were obtained from two other hospitals in Japan. Comprehensive microarray analysis was performed for all samples. Samples were divided into three sets. Candidate miRNAs for prostate cancer detection were identified in the discovery set (n = 123). A diagnostic model was con...
MicroRNA Profiling in Prostate Cancer - The Diagnostic Potential of Urinary miR-205 and miR-214
PLoS ONE, 2013
Prostate cancer (PCa) is the most common type of cancer in men in the United States, which disproportionately affects African American descents. While metastasis is the most common cause of death among PCa patients, no specific markers have been assigned to severity and ethnic biasness of the disease. MicroRNAs represent a promising new class of biomarkers owing to their inherent stability and resilience. In the present study, we investigated potential miRNAs that can be used as biomarkers and/or therapeutic targets and can provide insight into the severity and ethnic biasness of PCa. PCR array was performed in FFPE PCa tissues (5 Caucasian American and 5 African American) and selected differentially expressed miRNAs were validated by qRT-PCR, in 40 (15 CA and 25 AA) paired PCa and adjacent normal tissues. Significantly deregulated miRNAs were also analyzed in urine samples to explore their potential as non-invasive biomarker for PCa. Out of 8 miRNAs selected for validation from PCR array data, miR-205 (p,0.0001), mir-214 (p,0.0001), miR-221(p,0.001) and miR-99b (p,0.0001) were significantly downregulated in PCa tissues. ROC curve shows that all four miRNAs successfully discriminated between PCa and adjacent normal tissues. MiR-99b showed significant down regulation (p,0.01) in AA PCa tissues as compared to CA PCa tissues and might be related to the aggressiveness associated with AA population. In urine, miR-205 (p,0.05) and miR-214 (p,0.05) were significantly downregulated in PCa patients and can discriminate PCa patients from healthy individuals with 89% sensitivity and 80% specificity. In conclusion, present study showed that miR-205 and miR-214 are downregulated in PCa and may serve as potential non-invasive molecular biomarker for PCa. Citation: Srivastava A, Goldberger H, Dimtchev A, Ramalinga M, Chijioke J, et al. (2013) MicroRNA Profiling in Prostate Cancer -The Diagnostic Potential of Urinary miR-205 and miR-214. PLoS ONE 8(10): e76994.