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Holbrook KL, Lee WY. Volatile Organic Metabolites as Potential Biomarkers for Genitourinary Cancers: Review of the Applications and Detection Methods. Metabolites 2025; 15:37. [PMID: 39852380 PMCID: PMC11767221 DOI: 10.3390/metabo15010037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Revised: 01/07/2025] [Accepted: 01/08/2025] [Indexed: 01/26/2025] Open
Abstract
Cancer is one of the leading causes of death globally, and is ranked second in the United States. Early detection is crucial for more effective treatment and a higher chance of survival rates, reducing burdens on individuals and societies. Genitourinary cancers, in particular, face significant challenges in early detection. Finding new and cost-effective diagnostic methods is of clinical need. Metabolomic-based approaches, notably volatile organic compound (VOC) analysis, have shown promise in detecting cancer. VOCs are small organic metabolites involved in biological processes and disease development. They can be detected in urine, breath, and blood samples, making them potential candidates for sensitive and non-invasive alternatives for early cancer detection. However, developing robust VOC detection methods remains a hurdle. This review outlines the current landscape of major genitourinary cancers (kidney, prostate, bladder, and testicular), including epidemiology, risk factors, and current diagnostic tools. Furthermore, it explores the applications of using VOCs as cancer biomarkers, various analytical techniques, and comparisons of extraction and detection methods across different biospecimens. The potential use of VOCs in detection, monitoring disease progression, and treatment responses in the field of genitourinary oncology is examined.
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Affiliation(s)
| | - Wen-Yee Lee
- Department of Chemistry and Biochemistry, University of Texas at El Paso, El Paso, TX 79968, USA;
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2
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Mishra J, Chakraborty S, Nandi P, Manna S, Baral T, Niharika, Roy A, Mishra P, Patra SK. Epigenetic regulation of androgen dependent and independent prostate cancer. Adv Cancer Res 2024; 161:223-320. [PMID: 39032951 DOI: 10.1016/bs.acr.2024.05.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/23/2024]
Abstract
Prostate cancer is one of the most common malignancies among men worldwide. Besides genetic alterations, epigenetic modulations including DNA methylation, histone modifications and miRNA mediated alteration of gene expression are the key driving forces for the prostate tumor development and cancer progression. Aberrant expression and/or the activity of the epigenetic modifiers/enzymes, results in aberrant expression of genes involved in DNA repair, cell cycle regulation, cell adhesion, apoptosis, autophagy, tumor suppression and hormone response and thereby disease progression. Altered epigenome is associated with prostate cancer recurrence, progression, aggressiveness and transition from androgen-dependent to androgen-independent phenotype. These epigenetic modifications are reversible and various compounds/drugs targeting the epigenetic enzymes have been developed that are effective in cancer treatment. This chapter focuses on the epigenetic alterations in prostate cancer initiation and progression, listing different epigenetic biomarkers for diagnosis and prognosis of the disease and their potential as therapeutic targets. This chapter also summarizes different epigenetic drugs approved for prostate cancer therapy and the drugs available for clinical trials.
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Affiliation(s)
- Jagdish Mishra
- Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha, India
| | - Subhajit Chakraborty
- Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha, India
| | - Piyasa Nandi
- Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha, India
| | - Soumen Manna
- Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha, India
| | - Tirthankar Baral
- Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha, India
| | - Niharika
- Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha, India
| | - Ankan Roy
- Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha, India
| | - Prahallad Mishra
- Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha, India
| | - Samir Kumar Patra
- Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha, India.
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Palanisamy H, Manoharan JP, Vidyalakshmi S. Prognostic microRNAs as biomarkers for prostate cancer. J Cancer Res Ther 2024; 20:297-303. [PMID: 38554337 DOI: 10.4103/jcrt.jcrt_1469_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Accepted: 10/01/2022] [Indexed: 04/01/2024]
Abstract
OBJECTIVE Prostate cancer is the second largest cancer, most commonly diagnosed in men. Several studies reveal that miRNAs (microRNAs) are involved in various stages of prostate cancer. miRNAs are a family of small non-coding RNA species that have been implicated in the post-transcriptional regulation of gene expression. The present in silico study aims at identifying miRNA biomarkers that are significantly associated with the regulation of genes involved in prostate cancer. METHODS Dataset of miRNA and mRNA of prostate adenocarcinoma patients and controls was downloaded from The Cancer Genome Atlas (TCGA), and differential gene expression analysis was carried out. ROC and Kaplan-Meier survival analyses were performed on differentially expressed miRNAs. Pathway analysis was carried out for significant miRNAs, and protein-protein interaction of involved genes and miRNAs was examined. RESULTS A total of 185 miRNAs were differentially expressed between the patients and the control. ROC and Kaplan-Meier survival analysis showed that the two miRNAs hsa-mir-133b and hsa-mir-17-5p were found to be significantly associated with prostate cancer prognosis. HAS2 and EPHA10 gene targets of identified miRNA were also differentially expressed. A protein-protein interaction (PPI) network was constructed, and the HAS2 gene was found to be interacting with the epidermal growth factor receptor (EGFR). CONCLUSION This study highlights the potential of hsa-mir-133b and hsa-mir-17-5p miRNAs as biomarkers for the prognosis of prostate cancer. However, further experimental studies are required to validate this finding.
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Affiliation(s)
- Hema Palanisamy
- Department of Biotechnology, PSG College of Technology, Coimbatore Tamil Nadu, India
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Azani A, Omran SP, Ghasrsaz H, Idani A, Eliaderani MK, Peirovi N, Dokhani N, Lotfalizadeh MH, Rezaei MM, Ghahfarokhi MS, KarkonShayan S, Hanjani PN, Kardaan Z, Navashenagh JG, Yousefi M, Abdolahi M, Salmaninejad A. MicroRNAs as biomarkers for early diagnosis, targeting and prognosis of prostate cancer. Pathol Res Pract 2023; 248:154618. [PMID: 37331185 DOI: 10.1016/j.prp.2023.154618] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Revised: 06/09/2023] [Accepted: 06/10/2023] [Indexed: 06/20/2023]
Abstract
Globally, prostate cancer (PC) is leading cause of cancer-related mortality in men worldwide. Despite significant advances in the treatment and management of this disease, the cure rates for PC remains low, largely due to late detection. PC detection is mostly reliant on prostate-specific antigen (PSA) and digital rectal examination (DRE); however, due to the low positive predictive value of current diagnostics, there is an urgent need to identify new accurate biomarkers. Recent studies support the biological role of microRNAs (miRNAs) in the initiation and progression of PC, as well as their potential as novel biomarkers for patients' diagnosis, prognosis, and disease relapse. In the advanced stages, cancer-cell-derived small extracellular vesicles (SEVs) may constitute a significant part of circulating vesicles and cause detectable changes in the plasma vesicular miRNA profile. Recent computational model for the identification of miRNA biomarkers discussed. In addition, accumulating evidence indicates that miRNAs can be utilized to target PC cells. In this article, the current understanding of the role of microRNAs and exosomes in the pathogenesis and their significance in PC prognosis, early diagnosis, chemoresistance, and treatment are reviewed.
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Affiliation(s)
- Alireza Azani
- Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sima Parvizi Omran
- Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Haniyeh Ghasrsaz
- Faculty of Medicine, Mazandaran University of Medical Sciences, Mazandaran, Iran
| | - Asra Idani
- Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Niloufar Peirovi
- Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Negar Dokhani
- Student Research Committee, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | | | | | | | - Sepideh KarkonShayan
- Social Development and Health Promotion Research Center, Gonabad University of Medical Sciences, Gonabad, Iran
| | - Parisa Najari Hanjani
- Department of Genetics, Faculty of Advanced Technologies in Medicine, Golestan University of Medical Science, Gorgan, Iran
| | - Zahra Kardaan
- Department of Cellular Molecular Biology, Faculty of Life Science and Biotechnology, Shahid Beheshti University, Tehran, Iran
| | | | - Meysam Yousefi
- Department of Medical Genetics, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mitra Abdolahi
- Department of Pathology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Arash Salmaninejad
- Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Regenerative Medicine, Organ Procurement and Transplantation Multi-Disciplinary Center, Razi Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
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Ying M, Mao J, Sheng L, Wu H, Bai G, Zhong Z, Pan Z. Biomarkers for Prostate Cancer Bone Metastasis Detection and Prediction. J Pers Med 2023; 13:jpm13050705. [PMID: 37240875 DOI: 10.3390/jpm13050705] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Revised: 04/06/2023] [Accepted: 04/17/2023] [Indexed: 05/28/2023] Open
Abstract
Prostate cancer (PCa) causes deaths worldwide, ranking second after lung cancer. Bone metastasis (BM) frequently results from advanced PCa, affecting approximately 90% of patients, and it also often results in severe skeletal-related events. Traditional diagnostic methods for bone metastases, such as tissue biopsies and imaging, have substantial drawbacks. This article summarizes the significance of biomarkers in PCa accompanied with BM, including (1) bone formation markers like osteopontin (OPN), pro-collagen type I C-terminal pro-peptide (PICP), osteoprotegerin (OPG), pro-collagen type I N-terminal pro-peptide (PINP), alkaline phosphatase (ALP), and osteocalcin (OC); (2) bone resorption markers, including C-telopeptide of type I collagen (CTx), N-telopeptide of type I collagen (NTx), bone sialoprotein (BSP), tartrate-resistant acid phosphatase (TRACP), deoxypyridinoline (D-PYD), pyridoxine (PYD), and C-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP); (3) prostate-specific antigen (PSA); (4) neuroendocrine markers, such as chromogranin A (CgA), neuron-specific enolase (NSE), and pro-gastrin releasing peptide (ProGRP); (5) liquid biopsy markers, such as circulating tumor cells (CTCs), microRNA (miRNA), circulating tumor DNA (ctDNA), and cell-free DNA (cfDNA) and exosomes. In summary, some of these markers are already in widespread clinical use, while others still require further laboratory or clinical studies to validate their value for clinical application.
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Affiliation(s)
- Mingshuai Ying
- Department of Orthopaedic Surgery, The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu 322000, China
| | - Jianshui Mao
- Department of Orthopaedic Surgery, The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu 322000, China
| | - Lingchao Sheng
- Department of Orthopaedic Surgery, The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu 322000, China
| | - Hongwei Wu
- Department of Orthopaedic Surgery, The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu 322000, China
| | - Guangchao Bai
- Department of Orthopaedic Surgery, The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu 322000, China
| | - Zhuolin Zhong
- Department of Orthopaedic Surgery, The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu 322000, China
| | - Zhijun Pan
- Department of Orthopaedic Surgery, The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu 322000, China
- Department of Orthopaedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China
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Khan MM, Serajuddin M, Bharadwaj M. Potential plasma microRNAs signature miR-190b-5p, miR-215-5p and miR-527 as non-invasive biomarkers for prostate cancer. Biomarkers 2023; 28:227-237. [PMID: 36644827 DOI: 10.1080/1354750x.2022.2163694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
BackgroundProstate cancer (PCa) is the most prevalent (20%) pathological cancer among males globally. MicroRNAs (miRNAs) are short (19-22 nucleotide), conserved, noncoding molecules that regulate post-transcriptional processes either by repressing or degrading mRNA or by translation inhibition binding to complementary sites on mRNA. The goal of this study was to find out whether differentially expressed microRNA (DEM) could be used as a potential marker in the prognosis and diagnosis of PCa.MethodologyThe miRNAs profiling was done both from plasma and tissue samples of the same PCa patient (n = 3) by real-time quantitative PCR (qRT-PCR) and compared with BPH (benign prostatic hyperplasia) patients (n = 3) as controls and further validation of selected miRNAs.ResultsWe found 55 significant overexpressed DEMs, 44 significant underexpressed DEMs in plasma and 6 significant overexpressed DEMs, 27 significant underexpressed DEMs in tissue compared between PCa and BPH. Furthermore, there were eight miRNAs namely miR-190b, miR-215, miR-300, miR-329, miR-504, miR-525-3p, miR-527, miR-548a-3p found to be significantly differentially expressed in plasma and tissue samples via profiling, however only three showed concordant expression. After validation, miR-190b-5p were shown to be significantly downexpressed with fold changes of 0.4177 (p value - 0.0072) and 0.7264 (p value - 0.0143) in plasma and tissue samples, respectively. The expression of miR-215-5p was shown to be significantly overexpressed with fold change of 1.820 (p - 0.0016) and 1.476 (p - 0.0407) in plasma and tissue samples, respectively. Furthermore, miR-527 was shown to be significantly downexpressed with fold changes of 0.6018 (p - 0.0095) and 0.6917 (p - 0.0155) in plasma and tissue samples, respectively.ConclusionAccording to our findings, plasma miR-190b-5p, miR-215-5p, miR-527 levels alteration is consistently linked with PCa tissue. For establishing significant miRNAs as biomarkers, additional research of a larger population is needed.
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Affiliation(s)
- Mohd Mabood Khan
- Division of Molecular Genetics & Biochemistry, National Institute of Cancer Prevention & Research (ICMR-NICPR), Noida, India.,Department of Zoology, University of Lucknow, Lucknow, India
| | | | - Mausumi Bharadwaj
- Division of Molecular Genetics & Biochemistry, National Institute of Cancer Prevention & Research (ICMR-NICPR), Noida, India
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Klicka K, Grzywa TM, Mielniczuk A, Klinke A, Włodarski PK. The role of miR-200 family in the regulation of hallmarks of cancer. Front Oncol 2022; 12:965231. [PMID: 36158660 PMCID: PMC9492973 DOI: 10.3389/fonc.2022.965231] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Accepted: 08/04/2022] [Indexed: 11/16/2022] Open
Abstract
MiRNAs are short non-coding RNAs that regulate gene expression post-transcriptionally contributing to the development of different diseases including cancer. The miR-200 family consists of five members, miR-200a, miR-200b, miR-200c, miR-141, and miR-429. Their expression is dysregulated in cancer tissue and their level is altered in the body fluids of cancer patients. Moreover, the levels of miR-200 family members correlate with clinical parameters such as cancer patients' survival which makes them potentially useful as diagnostic and prognostic biomarkers. MiRNAs can act as either oncomiRs or tumor suppressor miRNAs depending on the target genes and their role in the regulation of key oncogenic signaling pathways. In most types of cancer, the miR-200 family acts as tumor suppressor miRNA and regulates all features of cancer. In this review, we summarized the expression pattern of the miR-200 family in different types of cancer and their potential utility as biomarkers. Moreover, we comprehensively described the role of miR-200 family members in the regulation of all hallmarks of cancer proposed by Hanahan and Weinberg with the focus on the epithelial-mesenchymal transition, invasiveness, and metastasis of tumor cells.
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Affiliation(s)
- Klaudia Klicka
- Department of Methodology, Medical University of Warsaw, Warsaw, Poland
- Doctoral School, Medical University of Warsaw, Warsaw, Poland
| | - Tomasz M. Grzywa
- Department of Methodology, Medical University of Warsaw, Warsaw, Poland
- Department of Immunology, Medical University of Warsaw, Warsaw, Poland
- Laboratory of Experimental Medicine, Medical University of Warsaw, Warsaw, Poland
| | | | - Alicja Klinke
- Department of Methodology, Medical University of Warsaw, Warsaw, Poland
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Coradduzza D, Solinas T, Balzano F, Culeddu N, Rossi N, Cruciani S, Azara E, Maioli M, Zinellu A, De Miglio MR, Madonia M, Falchi M, Carru C. miRNAs as molecular biomarkers for prostate cancer. J Mol Diagn 2022; 24:1171-1180. [PMID: 35835374 DOI: 10.1016/j.jmoldx.2022.05.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 04/05/2022] [Accepted: 05/23/2022] [Indexed: 01/10/2023] Open
Abstract
MicroRNAs (miRNAs) are short noncoding RNA able to regulate specific mRNA stability, thus influencing target gene expression. Disrupted levels of several miRNA have been associated with prostate cancer, the leading cause of cancer death among men and the fifth leading cause of death worldwide. Here, we investigated whether miR-145, miR-148, and miR-185 circulating levels in plasma could be used as molecular biomarkers, to allow distinguishing between individuals with benign prostatic hyperplasia, precancerous lesion, and prostate cancer. In this study, we recruited 170 urological clinic patients with suspected prostate cancer who underwent prostate biopsy. Total RNA was isolated from plasma, and TaqMan MicroRNA assays were used to analyze miR-145, miR-185, and miR-148 expression. First, differential miRNA expression among patient groups was evaluated. Then, miRNA levels were combined with clinical assessment outcomes, including results from invasive tests, using multivariate analysis to examine their ability in discriminating among the three patient groups. Our results suggest that miRNA is a promising molecular tool for clinical management of at-risk patients.
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Affiliation(s)
| | - Tatiana Solinas
- Urologic Clinic, Dep. of Clinical and Experimental Medicine, University of Sassari
| | - Francesca Balzano
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
| | - Nicola Culeddu
- Institute of Biomolecular Chemistry, National Research Council, Sassari, Italy
| | - Niccolò Rossi
- Department of Twin Research and Genetic Epidemiology, King's College London, London, UK
| | - Sara Cruciani
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
| | - Emanuela Azara
- Institute of Biomolecular Chemistry, National Research Council, Sassari, Italy
| | - Margherita Maioli
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
| | - Angelo Zinellu
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
| | | | - Massimo Madonia
- Urologic Clinic, Dep. of Clinical and Experimental Medicine, University of Sassari
| | - Mario Falchi
- Department of Twin Research and Genetic Epidemiology, King's College London, London, UK
| | - Ciriaco Carru
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy; University Hospital of Sassari (AOU), Sassari, Italy.
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The promising role of new molecular biomarkers in prostate cancer: from coding and non-coding genes to artificial intelligence approaches. Prostate Cancer Prostatic Dis 2022; 25:431-443. [PMID: 35422101 PMCID: PMC9385485 DOI: 10.1038/s41391-022-00537-2] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 03/24/2022] [Accepted: 03/30/2022] [Indexed: 12/15/2022]
Abstract
Background Risk stratification or progression in prostate cancer is performed with the support of clinical-pathological data such as the sum of the Gleason score and serum levels PSA. For several decades, methods aimed at the early detection of prostate cancer have included the determination of PSA serum levels. The aim of this systematic review is to provide an overview about recent advances in the discovery of new molecular biomarkers through transcriptomics, genomics and artificial intelligence that are expected to improve clinical management of the prostate cancer patient. Methods An exhaustive search was conducted by Pubmed, Google Scholar and Connected Papers using keywords relating to the genetics, genomics and artificial intelligence in prostate cancer, it includes “biomarkers”, “non-coding RNAs”, “lncRNAs”, “microRNAs”, “repetitive sequence”, “prognosis”, “prediction”, “whole-genome sequencing”, “RNA-Seq”, “transcriptome”, “machine learning”, and “deep learning”. Results New advances, including the search for changes in novel biomarkers such as mRNAs, microRNAs, lncRNAs, and repetitive sequences, are expected to contribute to an earlier and accurate diagnosis for each patient in the context of precision medicine, thus improving the prognosis and quality of life of patients. We analyze several aspects that are relevant for prostate cancer including its new molecular markers associated with diagnosis, prognosis, and prediction to therapy and how bioinformatic approaches such as machine learning and deep learning can contribute to clinic. Furthermore, we also include current techniques that will allow an earlier diagnosis, such as Spatial Transcriptomics, Exome Sequencing, and Whole-Genome Sequencing. Conclusion Transcriptomic and genomic analysis have contributed to generate knowledge in the field of prostate carcinogenesis, new information about coding and non-coding genes as biomarkers has emerged. Synergies created by the implementation of artificial intelligence to analyze and understand sequencing data have allowed the development of clinical strategies that facilitate decision-making and improve personalized management in prostate cancer.
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Diagnostic Value of microRNA-375 as Future Biomarker for Prostate Cancer Detection: A Meta-Analysis. Medicina (B Aires) 2022; 58:medicina58040529. [PMID: 35454368 PMCID: PMC9032467 DOI: 10.3390/medicina58040529] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 04/03/2022] [Accepted: 04/07/2022] [Indexed: 12/12/2022] Open
Abstract
Background and Objectives: Responding to the need for additional biomarkers for the diagnosis of prostate cancer (PCa), mounting studies show that microRNAs (miRNAs/miRs) possess great potential as future promising diagnostic tools. However, the usefulness of these miRNAs is still highly debated, as the degree of inconsistency between study designs and results is still elevated. Herein, we present a meta-analysis evaluating the diagnostic value and accuracy of circulating miR-375, as it is one of the most studied types of miRs in PCa. Materials and Methods: The diagnostic accuracy of miR-375 was evaluated using the QUADAS-2 tool, analyzing different statistical parameters. The seven studies (from six articles) that matched our selection included 422 PCa patients and 212 controls (70 healthy volunteers + 142 with benign prostate diseases). Results and Conclusion: We obtained a p-value of 0.76 for sensitivity, 0.83 for specificity, 16 for DOR, 4.6 for LR+, 0.29 for LR−, and 0.87 for AUC (95% CI 0.83–0.89). Our results confirm that miRNA-375 has high diagnostic potential for PCa, suggesting its usefulness as a powerful biomarker. More comprehensive studies are warranted to better assess its true value as a diagnostic biomarker for this urologic disease.
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Beyer K, Moris L, Lardas M, Haire A, Barletta F, Scuderi S, Molnar M, Herrera R, Rauf A, Campi R, Greco I, Shiranov K, Dabestani S, van den Broeck T, Arun S, Gacci M, Gandaglia G, Omar MI, MacLennan S, Roobol MJ, Farahmand B, Vradi E, Devecseri Z, Asiimwe A, Zong J, Maclennan SJ, Collette L, NDow J, Briganti A, Bjartell A, Van Hemelrijck M. Diagnostic and prognostic factors in patients with prostate cancer: a systematic review. BMJ Open 2022; 12:e058267. [PMID: 35379637 PMCID: PMC8981333 DOI: 10.1136/bmjopen-2021-058267] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVES As part of the PIONEER Consortium objectives, we have explored which diagnostic and prognostic factors (DPFs) are available in relation to our previously defined clinician and patient-reported outcomes for prostate cancer (PCa). DESIGN We performed a systematic review to identify validated and non-validated studies. DATA SOURCES MEDLINE, Embase and the Cochrane Library were searched on 21 January 2020. ELIGIBILITY CRITERIA Only quantitative studies were included. Single studies with fewer than 50 participants, published before 2014 and looking at outcomes which are not prioritised in the PIONEER core outcome set were excluded. DATA EXTRACTION AND SYNTHESIS After initial screening, we extracted data following the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of prognostic factor studies (CHARMS-PF) criteria and discussed the identified factors with a multidisciplinary expert group. The quality of the included papers was scored for applicability and risk of bias using validated tools such as PROBAST, Quality in Prognostic Studies and Quality Assessment of Diagnostic Accuracy Studies 2. RESULTS The search identified 6604 studies, from which 489 DPFs were included. Sixty-four of those were internally or externally validated. However, only three studies on diagnostic and seven studies on prognostic factors had a low risk of bias and a low risk concerning applicability. CONCLUSION Most of the DPFs identified require additional evaluation and validation in properly designed studies before they can be recommended for use in clinical practice. The PIONEER online search tool for DPFs for PCa will enable researchers to understand the quality of the current research and help them design future studies. ETHICS AND DISSEMINATION There are no ethical implications.
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Affiliation(s)
- Katharina Beyer
- Translational and Oncology Research (TOUR), King's College London, Faculty of Life Sciences and Medicine, London, UK
| | - Lisa Moris
- Department of Urology, University Hospitals Leuven, Leuven, Belgium
| | - Michael Lardas
- Department of Urology, Metropolitan Hospital, Athens, Greece
| | - Anna Haire
- Translational and Oncology Research (TOUR), King's College London, Faculty of Life Sciences and Medicine, London, UK
| | - Francesco Barletta
- Unit of Urology/Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Simone Scuderi
- Unit of Urology/Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
| | | | | | - Abdul Rauf
- Department of Urology, Mid Cheshire Hospitals, NHS Foundation Trust, Crewe, UK
| | - Riccardo Campi
- Department of Minimally Invasive and Robotic Urologic Surgery and Kidney Transplantation, University of Florence, Florence, Italy
| | - Isabella Greco
- Department of Minimally Invasive and Robotic Urologic Surgery and Kidney Transplantation, University of Florence, Florence, Italy
| | | | - Saeed Dabestani
- Dept. of Translational Medicine, Division of Urological Cancers, Lund University, Kristianstad Central Hospital, Malmo, Sweden
| | | | | | - Mauro Gacci
- Department of Minimally Invasive and Robotic Urologic Surgery and Kidney Transplantation, University of Florence, Florence, Italy
| | - Giorgio Gandaglia
- Unit of Urology/Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
| | | | | | - Monique J Roobol
- Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | | | | | | | | | - Jihong Zong
- Global Medical Affairs Oncology, Real World Evidence, Bayer HealthCare Pharmaceuticals Inc, Whippany, New Jersey, USA
| | | | | | - James NDow
- Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Alberto Briganti
- Unit of Urology/Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
- Department of Urology, University Vita e Salute-San Raffaele, Milan, Italy
| | - Anders Bjartell
- Department of Translational Medicine, Lund University, Malmö, Sweden
| | - Mieke Van Hemelrijck
- Translational and Oncology Research (TOUR), King's College London, Faculty of Life Sciences and Medicine, London, UK
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12
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Zhang WT, Zhang GX, Zhao RZ, Gao SS. The potential diagnostic accuracy of circulating microRNAs for prostate cancer: A meta-analysis. Actas Urol Esp 2022; 46:138-149. [PMID: 35260368 DOI: 10.1016/j.acuroe.2021.05.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 04/20/2021] [Accepted: 05/23/2021] [Indexed: 06/14/2023]
Abstract
OBJECTIVES This meta-analysis has been conducted to evaluate the diagnostic accuracy of circulating microRNAs for the early diagnosis of prostate cancer (PCA). METHODS A systematic literature search was performed (updated to February 18, 2021) in PubMed, EMBASE, Web of Science, Cochrane Library, Wanfang database and China National Knowledge Infrastructure (CNKI) to identify eligible studies. The pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under curve (AUC) of the summary receiver-operating characteristic (SROC) curve were calculated for both overall and subgroup analysis. The meta-regression and subgroup analysis were performed to explore heterogeneity and Deeks' funnel plot was used to assess publication bias. RESULTS One hundred nineteen studies from 33 articles owned 8703 PCA patients and 4914 controls were included in our meta-analysis. The overall sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under the curve were 0.79, 0.81, 4.1, 0.26, 16 and 0.87, respectively. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the curve of miR-21 in diagnosis of PCA were 0.86, 0.90, 8.3, 0.16, 52 and 0.94, respectively. Subgroup analysis suggested that the upregulated miRNA of serum type with large sample size could carry out a better diagnostic accuracy of PCA patients. Moreover, publication bias was not found. CONCLUSIONS Circulating microRNA, especially miR-21, can be used as a promising noninvasive biomarker in the early diagnosis of PCA.
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Affiliation(s)
- W T Zhang
- Xi'an Daxing Hospital, Shaanxi, China; International Doctoral School, University of Seville, Seville, Spain
| | - G X Zhang
- International Doctoral School, University of Seville, Seville, Spain
| | - R Z Zhao
- Ophthalmology Service, Hospital Hermanos Ameijeiras, La Habana, Cuba
| | - S S Gao
- Xi'an Daxing Hospital, Shaanxi, China; International Doctoral School, University of Seville, Seville, Spain.
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13
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La posible precisión diagnóstica de los microARN circulantes para el cáncer de próstata: un metaanálisis. Actas Urol Esp 2022. [DOI: 10.1016/j.acuro.2021.05.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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14
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Prognostic value of miR-21 for prostate cancer: a systematic review and meta-analysis. Biosci Rep 2021; 42:230521. [PMID: 34931228 PMCID: PMC8753345 DOI: 10.1042/bsr20211972] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 12/06/2021] [Accepted: 12/20/2021] [Indexed: 12/09/2022] Open
Abstract
Elevated levels of miR-21 expression are associated with many cancers, suggesting it may be a promising clinical biomarker. In prostate cancer (PCa), however, there is still no consensus about the usefulness of miR-21 as an indicator of disease progression. This systematic review and meta-analysis was conducted to investigate the value of miR-21 expression as a prognostic measurement in PCa patients. Medline (Ovid), EMBASE, Web of Science, Scopus and Cochrane Library databases were systematically searched for relevant publications between 2010 to 2021. Studies exploring the relationship between miR-21 expression, PCa prognosis and clinicopathological factors were selected for review. Those reporting hazard ratio (HR) and 95% confidence intervals (CIs) were subject to meta-analyses. Fixed-effect models were employed to calculated pooled HRs and 95% CIs. Risk of bias in each study was assessed using QUIPS tool. Certainty of evidence in each meta-analysis was assessed using GRADE guidelines. A total of 64 studies were included in the systematic review. Of these, 11 were eligible for inclusion in meta-analysis. Meta-analyses revealed that high miR-21 expression was associated with poor prognosis: HR = 1.58 (95% CI = 1.19–2.09) for biochemical recurrence, MODERATE certainty; HR = 1.46 (95% CI = 1.06–2.01) for death, VERY LOW certainty; and HR = 1.26 (95% CI = 0.70–2.27) for disease progression, VERY LOW certainty. Qualitative summary revealed elevated miR-21 expression was significantly positively associated with PCa stage, Gleason score and risk groups. This systematic review and meta-analysis suggests that elevated levels of miR-21 are associated with poor prognosis in PCa patients. miR-21 expression may therefore be a useful prognostic biomarker in this disease.
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15
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Cornice J, Capece D, Di Vito Nolfi M, Di Padova M, Compagnoni C, Verzella D, Di Francesco B, Vecchiotti D, Flati I, Tessitore A, Alesse E, Barbato G, Zazzeroni F. Ultrasound-Based Method for the Identification of Novel MicroRNA Biomarkers in Prostate Cancer. Genes (Basel) 2021; 12:genes12111726. [PMID: 34828332 PMCID: PMC8619582 DOI: 10.3390/genes12111726] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 10/26/2021] [Accepted: 10/27/2021] [Indexed: 11/16/2022] Open
Abstract
The detection of circulating microRNA (miRNA)-based biomarkers represents an innovative, non-invasive method for the early detection of cancer. However, the low concentration of miRNAs released in body fluids and the difficult identification of the tumor site have limited their clinical use as effective cancer biomarkers. To evaluate if ultrasound treatment could amplify the release of extracellular cancer biomarkers, we treated a panel of prostate cancer (PCa) cell lines with an ultrasound-based prototype and profiled the release of miRNAs in the extracellular space, with the aim of identifying novel miRNA-based biomarkers that could be used for PCa diagnosis and the monitoring of tumor evolution. We provide evidence that US-mediated sonoporation amplifies the release of miRNAs from both androgen-dependent (AD) and -independent (AI) PCa cells. We identified four PCa-related miRNAs, whose levels in LNCaP and DU145 supernatants were significantly increased following ultrasound treatment: mir-629-5p, mir-374-5p, mir-194-5p, and let-7d-5p. We further analyzed a publicly available dataset of PCa, showing that the serum expression of these novel miRNAs was upregulated in PCa patients compared to controls, thus confirming their clinical relevance. Our findings highlight the potential of using ultrasound to identify novel cell-free miRNAs released from cancer cells, with the aim of developing new biomarkers with diagnostic and predictive value.
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Affiliation(s)
- Jessica Cornice
- Department of Biotechnological and Applied Clinical Sciences (DISCAB), University of L’Aquila, 67100 L’Aquila, Italy; (J.C.); (M.D.V.N.); (M.D.P.); (C.C.); (D.V.); (B.D.F.); (D.V.); (I.F.); (A.T.); (E.A.); (F.Z.)
| | - Daria Capece
- Department of Biotechnological and Applied Clinical Sciences (DISCAB), University of L’Aquila, 67100 L’Aquila, Italy; (J.C.); (M.D.V.N.); (M.D.P.); (C.C.); (D.V.); (B.D.F.); (D.V.); (I.F.); (A.T.); (E.A.); (F.Z.)
- Correspondence: ; Tel.: +39-0862-433560
| | - Mauro Di Vito Nolfi
- Department of Biotechnological and Applied Clinical Sciences (DISCAB), University of L’Aquila, 67100 L’Aquila, Italy; (J.C.); (M.D.V.N.); (M.D.P.); (C.C.); (D.V.); (B.D.F.); (D.V.); (I.F.); (A.T.); (E.A.); (F.Z.)
| | - Monica Di Padova
- Department of Biotechnological and Applied Clinical Sciences (DISCAB), University of L’Aquila, 67100 L’Aquila, Italy; (J.C.); (M.D.V.N.); (M.D.P.); (C.C.); (D.V.); (B.D.F.); (D.V.); (I.F.); (A.T.); (E.A.); (F.Z.)
| | - Chiara Compagnoni
- Department of Biotechnological and Applied Clinical Sciences (DISCAB), University of L’Aquila, 67100 L’Aquila, Italy; (J.C.); (M.D.V.N.); (M.D.P.); (C.C.); (D.V.); (B.D.F.); (D.V.); (I.F.); (A.T.); (E.A.); (F.Z.)
| | - Daniela Verzella
- Department of Biotechnological and Applied Clinical Sciences (DISCAB), University of L’Aquila, 67100 L’Aquila, Italy; (J.C.); (M.D.V.N.); (M.D.P.); (C.C.); (D.V.); (B.D.F.); (D.V.); (I.F.); (A.T.); (E.A.); (F.Z.)
| | - Barbara Di Francesco
- Department of Biotechnological and Applied Clinical Sciences (DISCAB), University of L’Aquila, 67100 L’Aquila, Italy; (J.C.); (M.D.V.N.); (M.D.P.); (C.C.); (D.V.); (B.D.F.); (D.V.); (I.F.); (A.T.); (E.A.); (F.Z.)
| | - Davide Vecchiotti
- Department of Biotechnological and Applied Clinical Sciences (DISCAB), University of L’Aquila, 67100 L’Aquila, Italy; (J.C.); (M.D.V.N.); (M.D.P.); (C.C.); (D.V.); (B.D.F.); (D.V.); (I.F.); (A.T.); (E.A.); (F.Z.)
| | - Irene Flati
- Department of Biotechnological and Applied Clinical Sciences (DISCAB), University of L’Aquila, 67100 L’Aquila, Italy; (J.C.); (M.D.V.N.); (M.D.P.); (C.C.); (D.V.); (B.D.F.); (D.V.); (I.F.); (A.T.); (E.A.); (F.Z.)
| | - Alessandra Tessitore
- Department of Biotechnological and Applied Clinical Sciences (DISCAB), University of L’Aquila, 67100 L’Aquila, Italy; (J.C.); (M.D.V.N.); (M.D.P.); (C.C.); (D.V.); (B.D.F.); (D.V.); (I.F.); (A.T.); (E.A.); (F.Z.)
| | - Edoardo Alesse
- Department of Biotechnological and Applied Clinical Sciences (DISCAB), University of L’Aquila, 67100 L’Aquila, Italy; (J.C.); (M.D.V.N.); (M.D.P.); (C.C.); (D.V.); (B.D.F.); (D.V.); (I.F.); (A.T.); (E.A.); (F.Z.)
| | - Gaetano Barbato
- Inno-Sol srl, Via della Ricerca Scientifica snc, ed. PP1, 00133 Rome, Italy;
- Department of Biology, School of Pharmacy, University of Rome Tor Vergata, 00133 Rome, Italy
| | - Francesca Zazzeroni
- Department of Biotechnological and Applied Clinical Sciences (DISCAB), University of L’Aquila, 67100 L’Aquila, Italy; (J.C.); (M.D.V.N.); (M.D.P.); (C.C.); (D.V.); (B.D.F.); (D.V.); (I.F.); (A.T.); (E.A.); (F.Z.)
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16
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Shrivastava G, Aljabali AA, Shahcheraghi SH, Lotfi M, Shastri MD, Shukla SD, Chellappan DK, Jha NK, Anand K, Dureja H, Pabari RM, Mishra V, Almutary AG, Alnuqaydan AM, Charbe N, Prasher P, Negi P, Goyal R, Dua K, Gupta G, Serrano-Aroca Á, Bahar B, Barh D, Panda PK, Takayama K, Lundstorm K, McCarron P, Bakshi H, Tambuwala MM. Targeting LIN28: a new hope in prostate cancer theranostics. Future Oncol 2021; 17:3873-3880. [PMID: 34263659 DOI: 10.2217/fon-2021-0247] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Accepted: 06/17/2021] [Indexed: 11/21/2022] Open
Abstract
The mortality and morbidity rates for prostate cancer have recently increased to alarming levels, rising higher than lung cancer. Due to a lack of drug targets and molecular probes, existing theranostic techniques are limited. Human LIN28A and its paralog LIN28B overexpression are associated with a number of tumors resulting in a remarkable increase in cancer aggression and poor prognoses. The current review aims to highlight recent work identifying the key roles of LIN28A and LIN28B in prostate cancer, and to instigate further preclinical and clinical research in this important area.
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Affiliation(s)
- Garima Shrivastava
- Department of Biochemical Engineering & Biotechnology, Indian Institute of Technology, Delhi, Hauz Khas, New Delhi, India
| | - Alaa Aa Aljabali
- Department of Pharmaceutics & Pharmaceutical Technology, Yarmouk University, Irbid-Jordan
| | - Seyed Hossein Shahcheraghi
- Infectious Diseases Research Center, Shahid Sadoughi Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Marzieh Lotfi
- Infectious Diseases Research Center, Shahid Sadoughi Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Madhur D Shastri
- School of Pharmacy & Pharmacology, University of Tasmania, Hobart, Australia
| | - Shakti D Shukla
- Priority Research Centre for Healthy Lungs, School of Medicine & Public Health, The University of Newcastle, Callaghan, Australia
| | - Dinesh K Chellappan
- Department of Life Sciences, School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia
| | - Niraj Kumar Jha
- Department of Biotechnology, School of Engineering & Technology, Sharda University, Greater Noida, Uttar Pradesh, India
| | - Krishnan Anand
- Department of Chemical Pathology, School of Pathology, Faculty of Health Sciences & National Health Laboratory Service, University of the Free State, Bloemfontein, South Africa
| | - Harish Dureja
- Department of Chemistry, School of Science, GITAM University, Hyderabad 502329, India
| | - Ritesh M Pabari
- RCSI, University of Medicine & Health Sciences, Dublin, Ireland
| | - Vijay Mishra
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Abdulmajeed G Almutary
- Department of Medical Biotechnology, College of Applied Medical Sciences, Qassim University, Saudi Arabia
| | - Abdullah M Alnuqaydan
- Department of Medical Biotechnology, College of Applied Medical Sciences, Qassim University, Saudi Arabia
| | - Nitin Charbe
- Departamento de Química Orgánica, Facultad de Química y de Farmacia, Pontificia Universidad Católica de Chile, Santiago 340, Región Metropolitana, Chile
| | - Parteek Prasher
- Department of Chemistry, University of Petroleum & Energy Studies, Dehradun 248007, India
| | - Poonam Negi
- School of Pharmaceutical Sciences, Shoolini University of Biotechnology & Management Sciences, Solan 173229, India
| | - Rohit Goyal
- School of Pharmaceutical Sciences, Shoolini University of Biotechnology & Management Sciences, Solan 173229, India
| | - Kamal Dua
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo NSW 2007, Australia
| | - Gaurav Gupta
- School of Pharmaceutical Sciences, Suresh Gyan Vihar University, Jaipur, India
| | - Ángel Serrano-Aroca
- Biomaterials & Bioengineering Lab, Centro de Investigación Traslacional San Alberto Magno, Universidad Católica de Valencia, San Vicente Mártir, Valencia 46001, Spain
| | - Bojlul Bahar
- International Institute of Nutritional Sciences & Food Safety Studies, University of Central Lancashire, Preston, United Kingdom
| | - Debmalya Barh
- Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Pritam Kumar Panda
- Condensed Matter Theory Group, Materials Theory Division, Department of Physics & Astronomy, Uppsala University, Uppsala 75120, Sweden
| | - Kazuo Takayama
- Center for IPS Cell Research & Application, Kyoto University, Kyoto 606-8397, Japan
| | | | - Paul McCarron
- School of Pharmacy & Pharmaceutical Sciences, Ulster University, Coleraine, County Londonderry, Northern Ireland BT52 1SA, UK
| | - Hamid Bakshi
- School of Pharmacy & Pharmaceutical Sciences, Ulster University, Coleraine, County Londonderry, Northern Ireland BT52 1SA, UK
| | - Murtaza M Tambuwala
- School of Pharmacy & Pharmaceutical Sciences, Ulster University, Coleraine, County Londonderry, Northern Ireland BT52 1SA, UK
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17
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Sajjadi RS, Modarressi MH, Akbarian F, Tabatabaiefar MA. A Computational Framework to Infer Prostate Cancer-Associated Long Noncoding RNAs and Analyses for Identifying a Competing Endogenous RNA Network. Genet Test Mol Biomarkers 2021; 25:582-589. [PMID: 34550779 DOI: 10.1089/gtmb.2021.0053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Background: Prostate cancer (PC) is the second leading cause of cancer death after lung cancer in men. Current biomarkers are ineffective for the treatment and management of the disease. Long noncoding RNAs (lncRNAs) are a heterogeneous group of transcripts that are involved in complex gene expression regulatory networks. Although lncRNAs have been suggested to be promising as future biomarkers, the connection between the majority of lncRNAs and human disease remains to be elucidated. One approach to elucidate the roles of lncRNAs in disease is through the development of computational models. For example, a novel computational model termed HyperGeometric distribution for LncRNA-Disease Association (HGLDA) has been developed. Such models need to be developed on a tumor-specific basis to better suit the particular problem. Methods: In this study, we constructed a potential pipeline through two models, HGLDA and pathway-based using data from several databases. To validate the obtained data, the expression levels of selected lncRNAs were investigated quantitatively in the DU-145, LNCaP, and PC3 PC cell lines using quantitative real-time PCR. Results: We obtained a number of lncRNAs from both models, many of which were filtered through several databases that ultimately resulted in identification of six high-value lncRNA targets. Their expression was correlated with one important component of the PI3K pathway, known to be related to PC. Conclusion: Through the assembly of a lncRNA-miRNAs-mRNA competing endogenous RNA network, we successfully predicted lncRNAs interfering with miRNAs and coding genes related to PC.
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Affiliation(s)
- Roshanak S Sajjadi
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | | | - Fahimeh Akbarian
- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Amin Tabatabaiefar
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.,Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Noncommunicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
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18
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Prostate Cancer Biomarkers: From diagnosis to prognosis and precision-guided therapeutics. Pharmacol Ther 2021; 228:107932. [PMID: 34174272 DOI: 10.1016/j.pharmthera.2021.107932] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 05/10/2021] [Accepted: 05/12/2021] [Indexed: 12/23/2022]
Abstract
Prostate cancer (PCa) is one of the most commonly diagnosed malignancies and among the leading causes of cancer-related death worldwide. It is a highly heterogeneous disease, ranging from remarkably slow progression or inertia to highly aggressive and fatal disease. As therapeutic decision-making, clinical trial design and outcome highly depend on the appropriate stratification of patients to risk groups, it is imperative to differentiate between benign versus more aggressive states. The incorporation of clinically valuable prognostic and predictive biomarkers is also potentially amenable in this process, in the timely prevention of metastatic disease and in the decision for therapy selection. This review summarizes the progress that has so far been made in the identification of the genomic events that can be used for the classification, prediction and prognostication of PCa, and as major targets for clinical intervention. We include an extensive list of emerging biomarkers for which there is enough preclinical evidence to suggest that they may constitute crucial targets for achieving significant advances in the management of the disease. Finally, we highlight the main challenges that are associated with the identification of clinically significant PCa biomarkers and recommend possible ways to overcome such limitations.
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19
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Verdi J, Ketabchi N, Noorbakhsh N, Saleh M, Ebrahimi-Barough S, Seyhoun I, Kavianpour M. Development and Clinical Application of Tumor-derived Exosomes in Patients with Cancer. Curr Stem Cell Res Ther 2021; 17:91-102. [PMID: 34161212 DOI: 10.2174/1574888x16666210622123942] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 11/16/2020] [Accepted: 03/11/2021] [Indexed: 11/22/2022]
Abstract
A tumor is an abnormal growth of cells within a tissue that can lead to death due to late diagnosis, poor prognosis, drug resistance, and finally enhanced metastasis formation. Exosomes are nanovesicles that have been derived from all the different cell types. These vesicles can transfer various molecules, including the distinct form of nucleic acids (mRNA, miRNA, and circRNA) and proteins. Tumor-derived exosomes (TEXs) have exceptionally important roles through multiple molecular and cellular pathways like progression, tumorigenesis, drug resistance, and as well as metastasis. TEXs are detectable in all body fluids, such as serum and urine, a convenient and non-invasive way to access these nano-sized vesicles. TEXs lead to the symptom expression of genetic aberrations in the tumor cell population, making them an accurate and sensitive biomarker for the diagnosis and prognosis of tumors. On the other hand, TEXs contain major histocompatibility complexes (MHCs) and play important dual roles in regulating tumor immune responses; they can mediate both immune activation and suppression through tumor-associated immunity. Despite numerous scientific studies, there are still many technical barriers to distinguish TEXs from non-tumor-derived exosomes. Removing exosomes lead to a wide difference in outcomes inside a patient's body. Hence, controversial pieces of evidence have demonstrated the vital role of TEXs as hopeful biomarkers for the early detection of cancers, evaluation of therapeutic effects, and monitoring of the patient.
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Affiliation(s)
- Javad Verdi
- Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Neda Ketabchi
- Department of Medical Laboratory Sciences, Maragheh University of Medical Sciences, Maragheh, Iran
| | - Negar Noorbakhsh
- Department of Genetics, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Mahshid Saleh
- Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Somayeh Ebrahimi-Barough
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Iman Seyhoun
- Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Maria Kavianpour
- Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
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20
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Balázs K, Antal L, Sáfrány G, Lumniczky K. Blood-Derived Biomarkers of Diagnosis, Prognosis and Therapy Response in Prostate Cancer Patients. J Pers Med 2021; 11:296. [PMID: 33924671 PMCID: PMC8070149 DOI: 10.3390/jpm11040296] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 03/31/2021] [Accepted: 04/03/2021] [Indexed: 12/11/2022] Open
Abstract
Prostate cancer is among the most frequent cancers in men worldwide. Despite the fact that multiple therapeutic alternatives are available for its treatment, it is often discovered in an advanced stage as a metastatic disease. Prostate cancer screening is based on physical examination of prostate size and prostate-specific antigen (PSA) level in the blood as well as biopsy in suspect cases. However, these markers often fail to correctly identify the presence of cancer, or their positivity might lead to overdiagnosis and consequent overtreatment of an otherwise silent non-progressing disease. Moreover, these markers have very limited if any predictive value regarding therapy response or individual risk for therapy-related toxicities. Therefore, novel, optimally liquid biopsy-based (blood-derived) markers or marker panels are needed, which have better prognostic and predictive value than the ones currently used in the everyday routine. In this review the role of circulating tumour cells, extracellular vesicles and their microRNA content, as well as cellular and soluble immunological and inflammation- related blood markers for prostate cancer diagnosis, prognosis and prediction of therapy response is discussed. A special emphasis is placed on markers predicting response to radiotherapy and radiotherapy-related late side effects.
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Affiliation(s)
| | | | | | - Katalin Lumniczky
- Unit of Radiation Medicine, Department of Radiobiology and Radiohygiene, National Public Health Centre, 1221 Budapest, Hungary; (K.B.); (L.A.); (G.S.)
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21
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Yang Y, Liu KY, Liu Q, Cao Q. Androgen Receptor-Related Non-coding RNAs in Prostate Cancer. Front Cell Dev Biol 2021; 9:660853. [PMID: 33869227 PMCID: PMC8049439 DOI: 10.3389/fcell.2021.660853] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 03/12/2021] [Indexed: 12/20/2022] Open
Abstract
Prostate cancer (PCa) is the second leading cause of cancer-related death among men in the United States. Androgen receptor (AR) signaling is the dominant oncogenic pathway in PCa and the main strategy of PCa treatment is to control the AR activity. A large number of patients acquire resistance to Androgen deprivation therapy (ADT) due to AR aberrant activation, resulting in castration-resistant prostate cancer (CRPC). Understanding the molecular mechanisms underlying AR signaling in the PCa is critical to identify new therapeutic targets for PCa patients. The recent advances in high-throughput RNA sequencing (RNA-seq) techniques identified an increasing number of non-coding RNAs (ncRNAs) that play critical roles through various mechanisms in different diseases. Some ncRNAs have shown great potentials as biomarkers and therapeutic targets. Many ncRNAs have been investigated to regulate PCa through direct association with AR. In this review, we aim to comprehensively summarize recent findings of the functional roles and molecular mechanisms of AR-related ncRNAs as AR regulators or targets in the progression of PCa.
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Affiliation(s)
- Yongyong Yang
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.,Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | - Kilia Y Liu
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.,Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | - Qi Liu
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.,Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | - Qi Cao
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.,Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
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Konoshenko MY, Laktionov PP. MiRNAs and radical prostatectomy: Current data, bioinformatic analysis and utility as predictors of tumour relapse. Andrology 2021; 9:1092-1107. [PMID: 33638886 DOI: 10.1111/andr.12994] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 02/20/2021] [Accepted: 02/25/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND Studies of microRNAs (miRNAs) and genes have particular interest for cancer biology and medicine due to the discovery of new therapeutic targets and markers. These studies are extensively influenced by anticancer therapy, as miRNAs interfere with the therapy's efficacy in prostate cancer (PCa). OBJECTIVES In this article, we summarise the available data on the influence of radical prostatectomy (RP) and biochemical recurrence on miRNA expression. MATERIALS AND METHODS Molecular targets of these miRNAs, as well as the reciprocal relations between different miRNAs and their targets, were studied using the DIANA, STRING and TransmiR databases. Special attention was dedicated to the mechanisms of PCa development, miRNA, and associated genes as tumour development mediators. RESULTS AND DISCUSSION Combined analysis of the databases and available literature indicates that expression of four miRNAs that are associated with prostate cancer relapse and alter their expression after RP, combined with genes that closely interact with selected miRNAs, has high potential for the prediction of PCa relapse after RP. PCa tissues and biofluids, both immediately after RP for diagnostics/prognostics and in long-term (relapse) monitoring, may be used as sources of these miRNAs. CONCLUSION An overview of the usefulness of published data and bioinformatics resources looking for diagnostic markers and molecular targets is presented in this article. The selected miRNA and gene panels have good potential as prognostic and PCa relapse markers after RP and likely could also serve as markers for therapeutic efficiency on a broader scale.
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Affiliation(s)
- Maria Yu Konoshenko
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, Novosibirsk, Russia
| | - Pavel P Laktionov
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, Novosibirsk, Russia
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23
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Giglio S, De Nunzio C, Cirombella R, Stoppacciaro A, Faruq O, Volinia S, Baldassarre G, Tubaro A, Ishii H, Croce CM, Vecchione A. A preliminary study of micro-RNAs as minimally invasive biomarkers for the diagnosis of prostate cancer patients. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2021; 40:79. [PMID: 33622375 PMCID: PMC7903618 DOI: 10.1186/s13046-021-01875-0] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Accepted: 02/09/2021] [Indexed: 12/26/2022]
Abstract
Background A prostate cancer diagnosis is based on biopsy sampling that is an invasive, expensive procedure, and doesn’t accurately represent multifocal disease. Methods To establish a model using plasma miRs to distinguish Prostate cancer patients from non-cancer controls, we enrolled 600 patients histologically diagnosed as having or not prostate cancer at biopsy. Two hundred ninety patients were eligible for the analysis. Samples were randomly divided into discovery and validation cohorts. Results NGS-miR-expression profiling revealed a miRs signature able to distinguish prostate cancer from non-cancer plasma samples. Of 51 miRs selected in the discovery cohort, we successfully validated 5 miRs (4732-3p, 98-5p, let-7a-5p, 26b-5p, and 21-5p) deregulated in prostate cancer samples compared to controls (p ≤ 0.05). Multivariate and ROC analyses show miR-26b-5p as a strong predictor of PCa, with an AUC of 0.89 (CI = 0.83–0.95;p < 0.001). Combining miRs 26b-5p and 98-5p, we developed a model that has the best predictive power in discriminating prostate cancer from non-cancer (AUC = 0.94; CI: 0,835-0,954). To distinguish between low and high-grade prostate cancer, we found that miR-4732-3p levels were significantly higher; instead, miR-26b-5p and miR-98-5p levels were lower in low-grade compared to the high-grade group (p ≤ 0.05). Combining miR-26b-5p and miR-4732-3p we have the highest diagnostic accuracy for high-grade prostate cancer patients, (AUC = 0.80; CI 0,69-0,873). Conclusions Noninvasive diagnostic tests may reduce the number of unnecessary prostate biopsies. The 2-miRs-diagnostic model (miR-26b-5p and miR-98-5p) and the 2-miRs-grade model (miR-26b-5p and miR-4732-3p) are promising minimally invasive tools in prostate cancer clinical management. Supplementary Information The online version contains supplementary material available at 10.1186/s13046-021-01875-0.
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Affiliation(s)
- Simona Giglio
- University of Rome "Sapienza", Via di Grottarossa 1035, 00198, Rome, Italy
| | - Cosimo De Nunzio
- University of Rome "Sapienza", Via di Grottarossa 1035, 00198, Rome, Italy
| | - Roberto Cirombella
- University of Rome "Sapienza", Via di Grottarossa 1035, 00198, Rome, Italy
| | | | - Omar Faruq
- University of Rome "Sapienza", Via di Grottarossa 1035, 00198, Rome, Italy
| | - Stefano Volinia
- Department of morphological surgery and experimental medicine, Università degli Studi, Via Fossato di Mortara 64b, 44121, Ferrara, Italy
| | - Gustavo Baldassarre
- Division of Molecular Oncology, CRO National Cancer Institute, Via Franco Gallini, 2, 33081, Aviano, Italy
| | - Andrea Tubaro
- University of Rome "Sapienza", Via di Grottarossa 1035, 00198, Rome, Italy
| | - Hideshi Ishii
- Osaka University Graduate School of Medicine, Center of Medical Innovation and Translational Research (CoMIT: 081), Suita, Yamadaoka 2-2, Osaka, 565-0871, Japan
| | - Carlo M Croce
- Department of Cancer Genetics, The Ohio University, 460W12th Ave, Columbus, OH, 43210, USA
| | - Andrea Vecchione
- University of Rome "Sapienza", Via di Grottarossa 1035, 00198, Rome, Italy.
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24
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Parol M, Gzil A, Bodnar M, Grzanka D. Systematic review and meta-analysis of the prognostic significance of microRNAs related to metastatic and EMT process among prostate cancer patients. J Transl Med 2021; 19:28. [PMID: 33413466 PMCID: PMC7788830 DOI: 10.1186/s12967-020-02644-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Accepted: 11/27/2020] [Indexed: 02/07/2023] Open
Abstract
The ability of tumor cells to spread from their origin place and form secondary tumor foci is determined by the epithelial-mesenchymal transition process. In epithelial tumors such as prostate cancer (PCa), the loss of intercellular interactions can be observed as a change in expression of polarity proteins. Epithelial cells acquire ability to migrate, what leads to the formation of distal metastases. In recent years, the interest in miRNA molecules as potential future treatment options has increased. In tumor microenvironment, miRNAs have the ability to regulate signal transduction pathways, where they can act as suppressors or oncogenes. MiRNAs are secreted by cancer cells, and the changes in their expression levels are closely related to a cancer progression, including epithelial-mesenchymal transition. These molecules offer new diagnostic and therapeutic possibilities. Therapeutics which make use of synthesized RNA fragments and mimic or block miRNAs affected in PCa, may lead to inhibition of tumor progression and even disease re-emission. Based on appropriate qualification criteria, we conducted a selection process to identify scientific articles describing miRNAs and their relation to epithelial-mesenchymal transition in PCa patients. The studies were published in English on Pubmed, Scopus and the Web of Science before August 08, 2019. Hazard ratios (HRs) and 95% confidence intervals (CI) as well as total Gleason score were used to assess the concordance between miRNAs and presence of metastases. A total of 13 studies were included in our meta-analysis, representing 1608 PCa patients and 15 miRNA molecules. Our study clarifies a relationship between the clinicopathological features of PCa and the aberrant expression of several miRNA as well as the complex mechanism of miRNA molecules involvement in the induction and promotion of the metastatic mechanism in PCa.
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Affiliation(s)
- Martyna Parol
- Department of Clinical Pathomorphology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 9 Curie-Sklodowskiej Street, 85-094 Bydgoszcz, Poland
| | - Arkadiusz Gzil
- Department of Clinical Pathomorphology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 9 Curie-Sklodowskiej Street, 85-094 Bydgoszcz, Poland
| | - Magdalena Bodnar
- Department of Clinical Pathomorphology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 9 Curie-Sklodowskiej Street, 85-094 Bydgoszcz, Poland
| | - Dariusz Grzanka
- Department of Clinical Pathomorphology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 9 Curie-Sklodowskiej Street, 85-094 Bydgoszcz, Poland
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25
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Weissman R, Diamond EL, Haroche J, Pillar N, Shapira G, Durham BH, Buthorn J, Cohen F, Ki M, Stemer G, Ulaner GA, Amoura Z, Emile JF, Mazor RD, Shomron N, Abdel-Wahab OI, Shpilberg O, Hershkovitz-Rokah O. The Contribution of MicroRNAs to the Inflammatory and Neoplastic Characteristics of Erdheim-Chester Disease. Cancers (Basel) 2020; 12:E3240. [PMID: 33153128 PMCID: PMC7693724 DOI: 10.3390/cancers12113240] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 10/27/2020] [Accepted: 10/30/2020] [Indexed: 01/18/2023] Open
Abstract
The pathogenesis of histiocytic neoplasms is driven by mutations activating the MAPK/ERK pathway, but little is known about the transcriptional and post-transcriptional alterations involved in these neoplasms. We analyzed microRNA (miRNA) expression in plasma samples and tissue biopsies of Erdheim-Chester disease (ECD) and Langerhans cell histiocytosis (LCH) patients. In silico analysis revealed a potential role of miRNAs in regulating gene expression in these neoplasms as compared with healthy controls (HC). NanoString analysis revealed 101 differentially expressed plasma miRNAs in 16 ECD patients as compared with 11 HC, 95% of which were downregulated. MiRNAs-15a-5p, -15b-5p, -21-5p, -107, -221-3p, -320e, -630, and let-7 family miRNAs were further evaluated by qRT-PCR in an extended cohort of 32 ECD patients, seven LCH and 15 HC. Six miRNAs (let-7a, let-7c, miR-15a-5p, miR-15b-5p, miR-107 and miR-630) were highly expressed in LCH plasma and tissue samples as compared with ECD. Pathway enrichment analysis indicated the miRNA contribution to inflammatory and pro-survival signaling pathways. Moreover, the let-7 family members were downregulated in untreated ECD patients as compared with HC, while treatment with MAPK/ERK signaling inhibitors for 16 weeks resulted in their upregulation, which was in parallel with the radiologic response seen by PET-CT. The study highlights the potential contribution of miRNA to the inflammatory and neoplastic characteristics of ECD and LCH.
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Affiliation(s)
- Ran Weissman
- Department of Molecular Biology, Faculty of Natural Sciences, Ariel University, Ariel 40700, Israel;
- Translational Research Lab, Assuta Medical Centers, Tel-Aviv 6971028, Israel;
| | - Eli L. Diamond
- Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY 10016, USA; (E.L.D.); (J.B.)
| | - Julien Haroche
- Service de Médecine Interne, Hôpital Universitaire Pitié Salpêtrière-Charles Foix, Sorbonne Université, Faculté de Médecine, 75013 Paris, France; (J.H.); (F.C.); (Z.A.)
| | - Nir Pillar
- Department of Pathology, Hadassah Medical Center and Hebrew University, Jerusalem 91120, Israel;
| | - Guy Shapira
- Edmond J. Safra Center of Bioinformatics, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel; (G.S.); (N.S.)
| | - Benjamin H. Durham
- Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10016, USA; (B.H.D.); (M.K.); (O.I.A.-W.)
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10016; USA
| | - Justin Buthorn
- Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY 10016, USA; (E.L.D.); (J.B.)
| | - Fleur Cohen
- Service de Médecine Interne, Hôpital Universitaire Pitié Salpêtrière-Charles Foix, Sorbonne Université, Faculté de Médecine, 75013 Paris, France; (J.H.); (F.C.); (Z.A.)
| | - Michelle Ki
- Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10016, USA; (B.H.D.); (M.K.); (O.I.A.-W.)
| | - Galia Stemer
- HaEmek Medical Center, Department of Hematology, Afula 1834111, Israel;
| | - Gary A. Ulaner
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10016, USA;
| | - Zahir Amoura
- Service de Médecine Interne, Hôpital Universitaire Pitié Salpêtrière-Charles Foix, Sorbonne Université, Faculté de Médecine, 75013 Paris, France; (J.H.); (F.C.); (Z.A.)
| | - Jean-François Emile
- Research Unit EA4340, Versailles University, Paris-Saclay University, 92104 Boulogne, France;
- Pathology Department, Ambroise Paré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), 92104 Boulogne, France
| | - Roei D. Mazor
- Assuta Medical Centers, Institute of Hematology/Clinic of Histiocytic Neoplasms, Tel-Aviv 6971028, Israel;
| | - Noam Shomron
- Edmond J. Safra Center of Bioinformatics, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel; (G.S.); (N.S.)
| | - Omar I. Abdel-Wahab
- Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10016, USA; (B.H.D.); (M.K.); (O.I.A.-W.)
| | - Ofer Shpilberg
- Translational Research Lab, Assuta Medical Centers, Tel-Aviv 6971028, Israel;
- Assuta Medical Centers, Institute of Hematology/Clinic of Histiocytic Neoplasms, Tel-Aviv 6971028, Israel;
- Department of Medicine, Adelson School of Medicine, Ariel University, Ariel 40700, Israel
| | - Oshrat Hershkovitz-Rokah
- Department of Molecular Biology, Faculty of Natural Sciences, Ariel University, Ariel 40700, Israel;
- Translational Research Lab, Assuta Medical Centers, Tel-Aviv 6971028, Israel;
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Konoshenko MY, Bryzgunova OE, Lekchnov EA, Amelina EV, Yarmoschuk SV, Pak SV, Laktionov PP. The Influence of Radical Prostatectomy on the Expression of Cell-Free MiRNA. Diagnostics (Basel) 2020; 10:diagnostics10080600. [PMID: 32824612 PMCID: PMC7460220 DOI: 10.3390/diagnostics10080600] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2020] [Revised: 08/12/2020] [Accepted: 08/13/2020] [Indexed: 12/18/2022] Open
Abstract
MiRNAs of blood and urine have been shown to represent a convenient source of biomarkers for prostate cancer (PCa) diagnosis and assessment of the therapy effectiveness due to their high stability and representation and the low invasiveness of sample collection. Here, we studied the influence of radical prostatectomy (RP) on the expression of 12 cell-free miRNAs previously shown as potential markers of PCa (i.e., miR-19b, miR-22, miR-92a, miR-378, miR-425, miR-30e, miR-31, miR-125b, miR-200b, miR-205, miR-375 and miR-660). The relative expression of the miRNAs combined into 31 paired ratios was evaluated in the urine extracellular vesicles (EVs), clarified urine (CU) and blood plasma of healthy donors, pre- and post-RP samples of PCa patients. Nineteen miRNA ratios based on combinations of ten of the miRNAs (miR-19b, miR-30e, miR-31, miR-125b, miR-200b, miR-205, miR-375, miR-378, miR-425, and miR-660) were altered by RP. The comparative expression analysis of the cell-free miRNA ratios between healthy donors and PCa patients revealed miR-125b/miR-30e and miR-375/miR-30e as potential markers for evaluating therapeutic efficacy. MiR-378/miR-19b, miR-425/miR-19b, miR-200/miR-30e, miR-660/miR-30e, and miR-205/miR-30e had minor prognostic value but could be used to increase the steadiness of the diagnostic system. The urine EVs had the highest potential as a source of markers.
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Affiliation(s)
- Maria Yu. Konoshenko
- E.N. Meshalkin National Medical Research Center of the Ministry of Health of the Russian Federation, Novosibirsk 630055, Russia; (O.E.B.); (E.A.L.); (S.V.Y.); (S.V.P.); (P.P.L.)
- Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk 630090, Russia
- Correspondence: ; Tel.: +7-383-363-51-44
| | - Olga E. Bryzgunova
- E.N. Meshalkin National Medical Research Center of the Ministry of Health of the Russian Federation, Novosibirsk 630055, Russia; (O.E.B.); (E.A.L.); (S.V.Y.); (S.V.P.); (P.P.L.)
- Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk 630090, Russia
| | - Evgeniy A. Lekchnov
- E.N. Meshalkin National Medical Research Center of the Ministry of Health of the Russian Federation, Novosibirsk 630055, Russia; (O.E.B.); (E.A.L.); (S.V.Y.); (S.V.P.); (P.P.L.)
- Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk 630090, Russia
| | - Evgeniya V. Amelina
- The Center for Technology Transfer and Commercialization, Novosibirsk State University, Novosibirsk 630090, Russia;
| | - Sergey V. Yarmoschuk
- E.N. Meshalkin National Medical Research Center of the Ministry of Health of the Russian Federation, Novosibirsk 630055, Russia; (O.E.B.); (E.A.L.); (S.V.Y.); (S.V.P.); (P.P.L.)
| | - Svetlana V. Pak
- E.N. Meshalkin National Medical Research Center of the Ministry of Health of the Russian Federation, Novosibirsk 630055, Russia; (O.E.B.); (E.A.L.); (S.V.Y.); (S.V.P.); (P.P.L.)
| | - Pavel P. Laktionov
- E.N. Meshalkin National Medical Research Center of the Ministry of Health of the Russian Federation, Novosibirsk 630055, Russia; (O.E.B.); (E.A.L.); (S.V.Y.); (S.V.P.); (P.P.L.)
- Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk 630090, Russia
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Ciszkowicz E, Porzycki P, Semik M, Kaznowska E, Tyrka M. MiR-93/miR-375: Diagnostic Potential, Aggressiveness Correlation and Common Target Genes in Prostate Cancer. Int J Mol Sci 2020; 21:E5667. [PMID: 32784653 PMCID: PMC7460886 DOI: 10.3390/ijms21165667] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 07/29/2020] [Accepted: 08/05/2020] [Indexed: 12/15/2022] Open
Abstract
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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Affiliation(s)
- Ewa Ciszkowicz
- Faculty of Chemistry, Rzeszow University of Technology, 35-959 Rzeszów, Poland; (M.S.); (M.T.)
| | - Paweł Porzycki
- Department of Urology, Municipal Hospital in Rzeszów, 35-241 Rzeszów, Poland;
| | - Małgorzata Semik
- Faculty of Chemistry, Rzeszow University of Technology, 35-959 Rzeszów, Poland; (M.S.); (M.T.)
| | - Ewa Kaznowska
- Faculty of Medicine, University of Rzeszów, 35-959 Rzeszów, Poland;
| | - Mirosław Tyrka
- Faculty of Chemistry, Rzeszow University of Technology, 35-959 Rzeszów, Poland; (M.S.); (M.T.)
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Lei S, Peng F, Li ML, Duan WB, Peng CQ, Wu SJ. LncRNA-SMILR modulates RhoA/ROCK signaling by targeting miR-141 to regulate vascular remodeling in pulmonary arterial hypertension. Am J Physiol Heart Circ Physiol 2020; 319:H377-H391. [PMID: 32559140 DOI: 10.1152/ajpheart.00717.2019] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Pulmonary arterial hypertension (PAH) is a fatal progressive disease characterized by an increased blood pressure in the pulmonary arteries. RhoA/Rho-kinase (RhoA/ROCK) signaling activation is often associated with PAH. The purpose of this study is to investigate the role and mechanisms of long noncoding RNA (lncRNA) smooth muscle-induced lncRNA (SMILR) to activate the RhoA/ROCK pathway in PAH. SMILR, microRNA-141 (miR-141), and RhoA were identified by qRT-PCR in PAH patients' serum. 3-(4,5-Dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT), wound-healing assay, cell counting kit-8 (CCK-8) assay, and flow cytometry were performed to determine cell viability, migration, proliferation, and cell cycle in human pulmonary arterial smooth muscle cells (hPASMCs) and primary PASMCs from PAH patients. We also performed bioinformatical prediction, luciferase reporter assay, and RNA-binding protein immunoprecipitation (RIP) to assess the interaction among SMILR, miR-141, and RhoA. The RhoA/ROCK pathway and proliferation-related proteins were measured by Western blotting. Finally, we introduced the small hairpin (sh)SMILR to monocrotaline-induced PAH rat model and used the hemodynamic measurement, qRT-PCR, and immunohistochemistry to examine the therapeutic effects of shSMILR. SMILR and RhoA expression were upregulated, while miR-141 expression was downregulated in PAH patients. SMILR directly interacted with miR-141 and negatively regulated its expression. Knockdown of SMILR suppressed PASMC proliferation and migration induced by hypoxia. Furthermore, overexpression of miR-141 could inhibit the RhoA/ROCK pathway by binding to RhoA, thereby repressing cell proliferation-related signals. Knockdown of SMILR significantly inhibited the Rho/ROCK activation and vascular remodeling in monocrotaline-induced rats. Knockdown of SMILR effectively elevated miR-141 expression and in turn inhibited the RhoA/ROCK pathway to regulate vascular remodeling and reduce blood pressure in PAH.NEW & NOTEWORTHY Smooth muscle enriched long noncoding RNA (SMILR), as a long noncoding RNA (lncRNA), was increased in pulmonary arterial hypertension (PAH) patients and in vitro and in vivo models. SMILR activated RhoA/ROCK signaling by targeting miR-141 to disinhibit its downstream target RhoA. SMILR knockdown or miR-141 overexpression inhibited hypoxia-induced cell proliferation and migration via repressing RhoA/ROCK signaling in pulmonary arterial smooth muscle cells (PASMCs), which was confirmed in vivo experiments that knockdown of SMILR inhibited vascular remodeling and alleviated PAH in rats. SMILR may be a promising and novel therapeutic target for the treatment and drug development of PAH.
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Affiliation(s)
- Si Lei
- Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University; Research Unit of Respiratory Disease, Central South University; Hunan Centre for Evidence-based Medicine, Changsha, Hunan, China
| | - Fei Peng
- Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University; Research Unit of Respiratory Disease, Central South University; Hunan Centre for Evidence-based Medicine, Changsha, Hunan, China
| | - Mei-Lei Li
- Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University; Research Unit of Respiratory Disease, Central South University; Hunan Centre for Evidence-based Medicine, Changsha, Hunan, China
| | - Wen-Bing Duan
- Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University; Research Unit of Respiratory Disease, Central South University; Hunan Centre for Evidence-based Medicine, Changsha, Hunan, China
| | - Cai-Qin Peng
- Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University; Research Unit of Respiratory Disease, Central South University; Hunan Centre for Evidence-based Medicine, Changsha, Hunan, China
| | - Shang-Jie Wu
- Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University; Research Unit of Respiratory Disease, Central South University; Hunan Centre for Evidence-based Medicine, Changsha, Hunan, China
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Li J, Jin B, Wang T, Li W, Wang Z, Zhang H, Song Y, Li N. Serum microRNA expression profiling identifies serum biomarkers for HCV-related hepatocellular carcinoma. Cancer Biomark 2020; 26:501-512. [PMID: 31658041 DOI: 10.3233/cbm-181970] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND The identification of high-sensitivity biomarkers for detection of hepatocellular carcinoma (HCC) from high-risk individuals is essential. OBJECTIVE The present study was undertaken to identify and validate serum microRNAs (miRNAs) as potential biomarkers for hepatitis C virus (HCV)-related HCC. METHODS Illumina sequencing was employed to screen the expression profiles of miRNAs in serum samples of HCV-related HCC patients and liver cirrhosis (LC) patients. RT-qPCR was used to confirm the altered miRNAs between the two groups. Moreover, candidate miRNAs were examined in serum samples of 40 HCC patients, 54 LC patients, 55 patients with chronic HCV hepatitis and 45 healthy controls. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of the miRNAs for the detection of HCC. RESULTS Four miRNAs (miR-122-5p, miR-331-3p, miR-494-3p, miR-224-5p) were significantly increased and two miRNAs (miR-185-5p, miR-23b-3p) were significantly decreased in HCC patients compared to LC patients. ROC curve analysis demonstrated that the six miRNAs could be used as potential biomarkers for HCC detection. Combination of the six miRNAs could efficiently detect HCC in LC patients with the area under the ROC curve (AUC) of 0.995 and combination of the six miRNAs also provided high diagnostic accuracy (AUC = 0.961) for detection of HCC in non-HCC subjects. CONCLUSIONS The six serum miRNAs can be utilized as a surrogate and non-invasive biomarker for HCV-related HCC diagnosis.
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Affiliation(s)
- Jian Li
- Department of Hepatobiliary Surgery, Hospital Affiliated to Chengde Medical University, Chengde, Hebei, China.,Department of Hepatobiliary Surgery, You'an Hospital Affiliated to Capital Medical University, Beijing, China
| | - Boxun Jin
- Department of Hepatobiliary Surgery, You'an Hospital Affiliated to Capital Medical University, Beijing, China
| | - Tiezheng Wang
- Department of Hepatobiliary Surgery, You'an Hospital Affiliated to Capital Medical University, Beijing, China
| | - Wenlei Li
- Department of Hepatobiliary Surgery, You'an Hospital Affiliated to Capital Medical University, Beijing, China
| | - Zhenshun Wang
- Department of Hepatobiliary Surgery, You'an Hospital Affiliated to Capital Medical University, Beijing, China
| | - Haitao Zhang
- Department of Hepatobiliary Surgery, You'an Hospital Affiliated to Capital Medical University, Beijing, China
| | - Yunjun Song
- Department of Hepatobiliary Surgery, You'an Hospital Affiliated to Capital Medical University, Beijing, China
| | - Ning Li
- Department of Hepatobiliary Surgery, You'an Hospital Affiliated to Capital Medical University, Beijing, China
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Ye Y, Yuan XH, Wang JJ, Wang YC, Li SL. The diagnostic value of miRNA-141 in prostate cancer: A systematic review and PRISMA-compliant meta-analysis. Medicine (Baltimore) 2020; 99:e19993. [PMID: 32481368 DOI: 10.1097/md.0000000000019993] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND miR-141 has gradually demonstrated its value in the diagnosis of prostate cancer. However, the diagnostic parameters in previous studies differ. A systematic review was conducted to explore the diagnostic value of miR-141 in prostate cancer. METHODS A comprehensive search of the literature in the PubMed, Medline, Cochrane Library, and Embase databases was performed. The included 7 studies assessed the diagnostic value of miR-141 in patients with prostate cancer up to October 31, 2019. We used meta-disc version 1.4 and STATA software version 12.0 to analyze the data. RESULTS The pooled sensitivity and specificity were 0.70 (95% confidence interval [CI] 0.64-0.75) and 0.73 (95% CI 0.64-0.80), respectively. The positive likelihood ratio was 2.88 (95% CI 1.40-5.93), and the negative likelihood ratio was 0.38 (95% CI 0.20-0.71). Further, we note that the pooled diagnostic odds ratio of miR-141 for prostate cancer was 9.94 (95% CI: 2.55-38.80). The summary area under the receiver operating characteristic curve was 0.83 (95% CI: 0.79-0.86). The results of meta-regression suggested that heterogeneity was mainly derived from patient age. The results of the Fagan nomogram showed that it was increased significantly by testing miR-141 for diagnosing prostate cancer. CONCLUSION This meta-analysis suggests that miR-141 has a high diagnostic value for prostate cancer. In the future, large-scale prospective studies are needed to verify and evaluate this result.
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Affiliation(s)
- Yun Ye
- Department of Laboratory Medicine
| | | | - Jian-Jun Wang
- Emergency Department, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, China
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Abramovic I, Ulamec M, Katusic Bojanac A, Bulic-Jakus F, Jezek D, Sincic N. miRNA in prostate cancer: challenges toward translation. Epigenomics 2020; 12:543-558. [PMID: 32267174 DOI: 10.2217/epi-2019-0275] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Prostate cancer (PCa) represents the most commonly diagnosed neoplasm among men. miRNAs, as biomarkers, could further improve reliability in distinguishing malignant versus nonmalignant, and aggressive versus nonaggressive PCa. However, conflicting data was reported for certain miRNAs, and there was a lack of consistency and reproducibility, which has been attributed to diverse (pre)analytical factors. In order to address current challenges in miRNA clinical research on PCa, a PubMed-based literature search was conducted with the last update in May 2019. After identifying critical variations in designs and protocols that undermined clear-cut evidence acquisition, and reliable translation into clinical practice, we propose guidelines for most critical steps that should be considered in future research of miRNA as biomarkers, especially in PCa.
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Affiliation(s)
- Irena Abramovic
- Department of Medical Biology, University of Zagreb School of Medicine, Zagreb 10000, Croatia.,Scientific Group for Research on Epigenetic Biomarkers, University of Zagreb School of Medicine, Zagreb 10000, Croatia.,Scientific Centre of Excellence for Reproductive & Regenerative Medicine, University of Zagreb School of Medicine, Zagreb 10000, Croatia
| | - Monika Ulamec
- Scientific Group for Research on Epigenetic Biomarkers, University of Zagreb School of Medicine, Zagreb 10000, Croatia.,Ljudevit Jurak Clinical Department of Pathology & Cytology, University Clinical Hospital Center Sestre Milosrdnice, Zagreb 10000, Croatia.,Scientific Centre of Excellence for Reproductive & Regenerative Medicine, University of Zagreb School of Medicine, Zagreb 10000, Croatia.,Department of Pathology, University of Zagreb, School of Dental Medicine & School of Medicine, Zagreb 10000, Croatia
| | - Ana Katusic Bojanac
- Department of Medical Biology, University of Zagreb School of Medicine, Zagreb 10000, Croatia.,Scientific Centre of Excellence for Reproductive & Regenerative Medicine, University of Zagreb School of Medicine, Zagreb 10000, Croatia
| | - Floriana Bulic-Jakus
- Department of Medical Biology, University of Zagreb School of Medicine, Zagreb 10000, Croatia.,Scientific Centre of Excellence for Reproductive & Regenerative Medicine, University of Zagreb School of Medicine, Zagreb 10000, Croatia
| | - Davor Jezek
- Scientific Centre of Excellence for Reproductive & Regenerative Medicine, University of Zagreb School of Medicine, Zagreb 10000, Croatia.,Department of Histology & Embryology, University of Zagreb School of Medicine, Zagreb 10000, Croatia
| | - Nino Sincic
- Department of Medical Biology, University of Zagreb School of Medicine, Zagreb 10000, Croatia.,Scientific Group for Research on Epigenetic Biomarkers, University of Zagreb School of Medicine, Zagreb 10000, Croatia.,Scientific Centre of Excellence for Reproductive & Regenerative Medicine, University of Zagreb School of Medicine, Zagreb 10000, Croatia
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Perdas E, Stawski R, Kaczka K, Zubrzycka M. Analysis of Let-7 Family miRNA in Plasma as Potential Predictive Biomarkers of Diagnosis for Papillary Thyroid Cancer. Diagnostics (Basel) 2020; 10:diagnostics10030130. [PMID: 32121086 PMCID: PMC7151036 DOI: 10.3390/diagnostics10030130] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Revised: 02/25/2020] [Accepted: 02/26/2020] [Indexed: 12/17/2022] Open
Abstract
The most common histological type of thyroid cancer is papillary thyroid carcinoma (PTC). Radical resection of the thyroid gland is currently the recommended method of treatment. Almost 75% of thyroidectomies performed just for diagnostic purposes are benign. Thus, the confirmation of innovative and more precise noninvasive biomarkers holds promise for the detection of PTC, which may decrease the number of unnecessary thyroid lobectomies. In this work, using the droplet digital PCR (ddPCR) method, we have analyzed the level of five miRNAs (let-7a, let-7c, let-7d, let-7f, and let-7i) in the plasma of patients with PTC and compared them with those of a healthy control group to investigate whether miRNAs also have value in the management of PTC. Levels of four miRNAs, namely let-7a, let-7c, let-7d, and let-7f, were significantly higher in PTC patients than healthy controls. Thus, the analysis of circulating let-7 can be a useful tool and support the currently used methods for PTC diagnosis. However, our observation requires further research on a larger patient group.
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Affiliation(s)
- Ewelina Perdas
- Department of Cardiovascular Physiology, Faculty of Medicine, Medical University of Lodz, 92-215 Lodz, Poland; (E.P.)
| | - Robert Stawski
- Department of Clinical Physiology, Faculty of Medicine, Medical University of Lodz, 92-215 Lodz, Poland
- Correspondence: ; Tel.: +48-422-725-956
| | - Krzysztof Kaczka
- Department of General and Oncological Surgery, Medical University of Lodz, 92-213 Lodz, Poland;
| | - Maria Zubrzycka
- Department of Cardiovascular Physiology, Faculty of Medicine, Medical University of Lodz, 92-215 Lodz, Poland; (E.P.)
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MiRNA-Based Inspired Approach in Diagnosis of Prostate Cancer. ACTA ACUST UNITED AC 2020; 56:medicina56020094. [PMID: 32102477 PMCID: PMC7074198 DOI: 10.3390/medicina56020094] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Revised: 02/10/2020] [Accepted: 02/19/2020] [Indexed: 12/14/2022]
Abstract
Prostate cancer is one of the most encountered cancer diseases in men worldwide and in consequence it requires the improvement of therapeutic strategies. For the clinical diagnosis, the standard approach is represented by solid biopsy. From a surgical point of view, this technique represents an invasive procedure that may imply several postoperative complications. To overcome these impediments, many trends are focusing on developing liquid biopsy assays and on implementing them in clinical practice. Liquid samples (blood, urine) are rich in analytes, especially in transcriptomic information provided by genetic markers. Additionally, molecular characterization regarding microRNAs content reveals outstanding prospects in understanding cancer progression mechanisms. Moreover, these analytes have great potential for prostate cancer early detection, more accurate prostate cancer staging and also for decision making respecting therapy schemes. However, there are still questionable topics and more research is needed to standardize liquid biopsy-based techniques.
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Quirico L, Orso F. The power of microRNAs as diagnostic and prognostic biomarkers in liquid biopsies. CANCER DRUG RESISTANCE (ALHAMBRA, CALIF.) 2020; 3:117-139. [PMID: 35582611 PMCID: PMC9090592 DOI: 10.20517/cdr.2019.103] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Revised: 01/24/2020] [Accepted: 02/07/2020] [Indexed: 02/06/2023]
Abstract
In the last decades, progresses in medical oncology have ameliorated the treatment of patients and their outcome. However, further improvements are still necessary, in particular for certain types of tumors such as pancreatic, gastric, and lung cancer as well as acute myeloid leukemia where early detection and monitoring of the disease are crucial for final patient outcome. Liquid biopsy represents a great advance in the field because it is less invasive, less time-consuming, and safer compared to classical biopsies and it can be useful to monitor the evolution of the disease as well as the response of patients to therapy. Liquid biopsy allows the detection of circulating tumor cells, nucleic acids, and exosomes not only in blood but also in different biological fluids: urine, saliva, pleural effusions, cerebrospinal fluid, and stool. Among the potential biomarkers detectable in liquid biopsies, microRNAs (miRNAs) are gaining more and more attention, since they are easily detectable, quite stable in biological fluids, and show high sensitivity. Many data demonstrate that miRNAs alone or in combination with other biomarkers could improve the diagnostic and prognostic power for many different tumors. Despite this, standardization of methods, sample preparation, and analysis remain challenging and a huge effort should be made to address these issues before miRNA biomarkers can enter the clinic. This review summarizes the main findings in the field of circulating miRNAs in both solid and hematological tumors.
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Affiliation(s)
- Lorena Quirico
- Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino 10126, Italy
- Molecular Biotechnology Center (MBC), University of Torino, Torino 10126, Italy
| | - Francesca Orso
- Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino 10126, Italy
- Molecular Biotechnology Center (MBC), University of Torino, Torino 10126, Italy
- Center for Complex Systems in Molecular Biology and Medicine, University of Torino, Torino 10126, Italy
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Sun Q, Li J, Jin B, Wang T, Gu J. Evaluation of miR-331-3p and miR-23b-3p as serum biomarkers for hepatitis c virus-related hepatocellular carcinoma at early stage. Clin Res Hepatol Gastroenterol 2020; 44:21-28. [PMID: 31053500 DOI: 10.1016/j.clinre.2019.03.011] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Revised: 03/21/2019] [Accepted: 03/26/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS This study aimed to investigate the diagnostic values of serum miR-331-3p and miR-23b-3p as tumor markers for the diagnosis of hepatocellular carcinoma (HCC) at early stage. METHODS A total of 191 subjects were enrolled and consisted of 45 healthy controls (HC), 106 hepatitis c virus (HCV)-related chronic liver disease (CLD) patients, and 40 early-stage HCC patients. CLD patients were subdivided according to Metavir fibrosis-scoring. Serum miR-331-3p and miR-23b-3p were measured. The area under curves (AUC) was calculated for each microRNA and compared with that for alpha-fetoprotein (AFP) in the detection of HCC at early stage. RESULTS Serum miR-331-3p was significantly higher in early-stage HCC than that in CLD and HC respectively, and it decreased significantly after surgery in early-stage HCC. Contrarily, serum miR-23b-3p was significantly lower in early-stage HCC and increased significantly after surgery. Further, receiver operating characteristic analysis demonstrated AUC was 0.806 (95%CI: 0.728-0.883; sensitivity: 85.85%, specificity: 65.00%) for serum miR-23b-3p in discriminating early-stage HCC from CLD patients, higher than that for AFP (AUC:0.660, 95%CI: 0.556-0.764; sensitivity: 70.00%, specificity: 56.60%). In discrimination early-stage HCC from severe fibrosis/cirrhosis (F3 + F4) patients, both miR-23b-3p (AUC: 0.796, 95%CI: 0.703-0.889; sensitivity: 85.11%, specificity: 65.00%) and miR-331-3p (AUC:0.832, 95%CI: 0.812-0.953; sensitivity: 75.00%, specificity: 85.11%) had better diagnostic performances than AFP (AUC:0.632, 95%CI: 0.512-0.753; sensitivity: 50.00%, specificity: 55.32%). Serum miR-331-3p levels also showed a significant correlation with BCLC stages of HCC. CONCLUSION Serum miR-331-3p and miR-23b-3p could be used as novel invasive biomarkers in the early detection of HCC in high-risk patients.
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Affiliation(s)
- Qiyu Sun
- Department of Clinical Laboratory, Affiliated Hospital of Chengde Medical University, 36, Nanyingzi Road, Chengde, 067000, PR China.
| | - Jian Li
- Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, 36, Nanyingzi Road, Chengde, 067000, PR China
| | - Boxun Jin
- Department of Hepatobiliary Surgery, YouAn Hospital Affiliated to Capital Medical University, 8, Xitoutiao Road, Beijing, 100069, PR China
| | - Tiezheng Wang
- Department of Hepatobiliary Surgery, YouAn Hospital Affiliated to Capital Medical University, 8, Xitoutiao Road, Beijing, 100069, PR China
| | - Jiannan Gu
- Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, 36, Nanyingzi Road, Chengde, 067000, PR China
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Elemeery MN, Mohamed MA, Madkour MA, Shamseya MM, Issa NM, Badr AN, Ghareeb DA, Pan CH. MicroRNA signature in patients with hepatocellular carcinoma associated with type 2 diabetes. World J Gastroenterol 2019; 25:6322-6341. [PMID: 31754293 PMCID: PMC6861851 DOI: 10.3748/wjg.v25.i42.6322] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 10/29/2019] [Accepted: 11/07/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Nonalcoholic steatohepatitis-related cirrhosis is one of the liver complications in type 2 diabetes mellitus (T2DM) and reported to be a risk factor for developing hepatocellular carcinoma (HCC). A reliable screening biomarker of liver cirrhosis (LC) and HCC among T2DM patients is important to reduce the morbidity and mortality of this disease. MicroRNA (miRNA) is considered a key player in HCC and T2DM, and it might be a hidden culprit in diabetes-associated HCC, making it a promising reliable prognostic tool.
AIM To investigate the signature of serum miRNAs as early biomarkers for the screening of HCC among diabetic patients.
METHODS Expression profiles of miRNAs in serum samples of diabetic LC and diabetic HCC patients were assessed using Illumina sequencing; then, RT-qPCR was used to validate significantly altered miRNAs between the two groups. Candidate miRNAs were tested in serum samples of 200 T2DM patients, 270 LC patients, 200 HCC patients, and 225 healthy control subjects. Additionally, receiver operating characteristic (ROC) analysis, with area under the curve (AUC), was performed to assess the diagnostic performance of the screened miRNAs for discriminating HCC from LC and nonmalignant patients (LC + T2DM).
RESULTS Expression of the sequenced miRNAs in serum was different in HCC vs LC-positive T2DM patients. Two miRNAs (miR-34a, miR-221) were significantly up-regulated and five miRNAs (miR-16, miR-23-3p, miR-122-5p, miR-198, miR-199a-3p) were significantly down-regulated in HCC compared to LC patients. Analysis of ROC curve demonstrated that the combination of these seven miRNAs can be used as a reliable biomarker for detection of HCC in diabetic patients, as it could identify HCC with high diagnostic accuracy in diabetic LC patients (AUC = 0.993) and in diabetic nonmalignant patients (AUC = 0.961).
CONCLUSION This study validates a panel of serum miRNAs that can be used as a reliable noninvasive screening biomarker of HCC among T2DM cirrhotic and noncirrhotic patients. The study recommends further research to shed light on a possible role of c-Met in T2DM-associated HCC via the miRNA regulatory pathway.
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Affiliation(s)
- Moustafa Nouh Elemeery
- Département de Neurosciences, CRCHUM, Université de Montréal, Montréal, Quebec H2X 3E4, Canada
- Medical Biotechnology Laboratory, Genetic Engineering and Biotechnology Research Division, National Research Centre, Cairo 12622, Egypt
- Natural Product Informatics Research Center, KIST Gangneung Institute of Natural Products, Gangneung 25451, South Korea
- Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology, Seoul 02792, South Korea
| | - Marwa Anwar Mohamed
- Department of Chemical Pathology, Medical Research Institute, Alexandria University, Alexandria 21511, Egypt
| | - Marwa Ahmed Madkour
- Experimental and Clinical Internal Medicine Department, Medical Research Institute, Alexandria University, Alexandria 21511, Egypt
| | - Mohammed Mohammed Shamseya
- Experimental and Clinical Internal Medicine Department, Medical Research Institute, Alexandria University, Alexandria 21511, Egypt
| | - Noha Mahmoud Issa
- Human Genetics Department, Medical Research Institute, Alexandria University, Alexandria 21511, Egypt
| | - Ahmed Noah Badr
- Food Toxicology and Contaminates Department, National Research Centre, Dokki, Cairo 12622, Egypt
| | - Doaa Ahmed Ghareeb
- Bioscreening and preclinical trial lab, Biochemistry Department, Faculty of Science, Alexandria University, Alexandria 12522, Egypt
- Pharmaceutical and fermentation industries development center, the city of scientific research and technological applications, Alexandria 26411, Egypt
| | - Cheol-Ho Pan
- Natural Product Informatics Research Center, KIST Gangneung Institute of Natural Products, Gangneung 25451, South Korea
- Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology, Seoul 02792, South Korea
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Ikert H, Craig PM. Chronic exposure to venlafaxine and increased water temperature reversibly alters microRNA in zebrafish gonads (Danio rerio). COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY D-GENOMICS & PROTEOMICS 2019; 33:100634. [PMID: 31715506 DOI: 10.1016/j.cbd.2019.100634] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Revised: 10/09/2019] [Accepted: 10/12/2019] [Indexed: 01/28/2023]
Abstract
MicroRNA (miRNA) are short, non-coding RNA that act by downregulating targeted mRNA transcripts. Only recently have they been used as endpoints in studies of aquatic toxicology. The purpose of this study was to determine the effect of an antidepressant contaminant, venlafaxine (VFX), and increased temperature on specific microRNA levels in zebrafish (Danio rerio) reproductive tissue. Adult zebrafish were exposed to one of four conditions; control, 1 μg/L VFX (VFX), 32 °C (Temp), or 1 μg/L VFX + 32 °C (VFX & Temp) for 21 days. Half of the fish were returned to control conditions for a 21-day recovery period. RT-qPCR was performed to measure relative abundances of several miRNAs known to respond to antidepressant exposure: dre-miR-22b-3p, dre-miR-301a, dre-miR-140-5p, dre-let-7d-5p, dre-miR-210-5p, and dre-miR-457b-5p. After the exposure period, dre-miR-22b-3p and dre-miR-301a showed a significant downregulation in response to all treatments. In contrast, after the recovery period, there were no significant differences in microRNA abundance. These altered microRNA are predicted to target several genes, including phosphofructokinase, and are associated with ovarian pathologies. Combined, we have shown that VFX and increased water temperature alter miRNA abundances in zebrafish reproductive tissue, an effect correlated with a functional stress response and cell cycle dysregulation.
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Affiliation(s)
- Heather Ikert
- Department of Biology, University of Waterloo, 200 University Ave. W., Waterloo, Ontario N2L 3G1, Canada.
| | - Paul M Craig
- Department of Biology, University of Waterloo, 200 University Ave. W., Waterloo, Ontario N2L 3G1, Canada.
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Boerrigter E, Groen LN, Van Erp NP, Verhaegh GW, Schalken JA. Clinical utility of emerging biomarkers in prostate cancer liquid biopsies. Expert Rev Mol Diagn 2019; 20:219-230. [DOI: 10.1080/14737159.2019.1675515] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Affiliation(s)
- Emmy Boerrigter
- Department of Pharmacy, Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, The Netherlands
| | - Levi N. Groen
- Department of Experimental Urology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands
| | - Nielka P. Van Erp
- Department of Pharmacy, Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, The Netherlands
| | - Gerald W. Verhaegh
- Department of Experimental Urology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands
| | - Jack A. Schalken
- Department of Experimental Urology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands
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Bottani M, Banfi G, Lombardi G. Circulating miRNAs as Diagnostic and Prognostic Biomarkers in Common Solid Tumors: Focus on Lung, Breast, Prostate Cancers, and Osteosarcoma. J Clin Med 2019; 8:E1661. [PMID: 31614612 PMCID: PMC6833074 DOI: 10.3390/jcm8101661] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Revised: 10/04/2019] [Accepted: 10/06/2019] [Indexed: 12/22/2022] Open
Abstract
An early cancer diagnosis is essential to treat and manage patients, but it is difficult to achieve this goal due to the still too low specificity and sensitivity of classical methods (imaging, actual biomarkers), together with the high invasiveness of tissue biopsies. The discovery of novel, reliable, and easily collectable cancer markers is a topic of interest, with human biofluids, especially blood, as important sources of minimal invasive biomarkers such as circulating microRNAs (miRNAs), the most promising. MiRNAs are small non-coding RNAs and known epigenetic modulators of gene expression, with specific roles in cancer development/progression, which are next to be implemented in the clinical routine as biomarkers for early diagnosis and the efficient monitoring of tumor progression and treatment response. Unfortunately, several issues regarding their validation process are still to be resolved. In this review, updated findings specifically focused on the clinical relevance of circulating miRNAs as prognostic and diagnostic biomarkers for the most prevalent cancer types (breast, lung, and prostate cancers in adults, and osteosarcoma in children) are described. In addition, deep analysis of pre-analytical, analytical, and post-analytical issues still affecting the circulation of miRNAs' validation process and routine implementation is included.
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Affiliation(s)
- Michela Bottani
- IRCCS Istituto Ortopedico Galeazzi, Laboratory of Experimental Biochemistry and Molecular Biology, Via Riccardo Galeazzi 4, 20161 Milano, Italy.
| | - Giuseppe Banfi
- IRCCS Istituto Ortopedico Galeazzi, Laboratory of Experimental Biochemistry and Molecular Biology, Via Riccardo Galeazzi 4, 20161 Milano, Italy.
- Vita-Salute San Raffaele University, 20132 Milano, Italy.
| | - Giovanni Lombardi
- IRCCS Istituto Ortopedico Galeazzi, Laboratory of Experimental Biochemistry and Molecular Biology, Via Riccardo Galeazzi 4, 20161 Milano, Italy.
- Dept. of Physiology and Pharmacology, Gdańsk University of Physical Education and Sport, Gdańsk, ul. Kazimierza Górskiego 1, 80-336 Pomorskie, Poland.
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Zeuschner P, Linxweiler J, Junker K. Non-coding RNAs as biomarkers in liquid biopsies with a special emphasis on extracellular vesicles in urological malignancies. Expert Rev Mol Diagn 2019; 20:151-167. [DOI: 10.1080/14737159.2019.1665998] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Philip Zeuschner
- Department of Urology and Pediatric Urology, Saarland University, Homburg, Germany
| | - Johannes Linxweiler
- Department of Urology and Pediatric Urology, Saarland University, Homburg, Germany
| | - Kerstin Junker
- Department of Urology and Pediatric Urology, Saarland University, Homburg, Germany
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Chirshev E, Oberg KC, Ioffe YJ, Unternaehrer JJ. Let-7 as biomarker, prognostic indicator, and therapy for precision medicine in cancer. Clin Transl Med 2019; 8:24. [PMID: 31468250 PMCID: PMC6715759 DOI: 10.1186/s40169-019-0240-y] [Citation(s) in RCA: 172] [Impact Index Per Article: 28.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Accepted: 08/16/2019] [Indexed: 12/23/2022] Open
Abstract
Abnormal regulation and expression of microRNAs (miRNAs) has been documented in various diseases including cancer. The miRNA let-7 (MIRLET7) family controls developmental timing and differentiation. Let-7 loss contributes to carcinogenesis via an increase in its target oncogenes and stemness factors. Let-7 targets include genes regulating the cell cycle, cell signaling, and maintenance of differentiation. It is categorized as a tumor suppressor because it reduces cancer aggressiveness, chemoresistance, and radioresistance. However, in rare situations let-7 acts as an oncogene, increasing cancer migration, invasion, chemoresistance, and expression of genes associated with progression and metastasis. Here, we review let-7 function as tumor suppressor and oncogene, considering let-7 as a potential diagnostic and prognostic marker, and a therapeutic target for cancer treatment. We explain the complex regulation and function of different let-7 family members, pointing to abnormal processes involved in carcinogenesis. Let-7 is a promising option to complement conventional cancer therapy, but requires a tumor specific delivery method to avoid toxicity. While let-7 therapy is not yet established, we make the case that assessing its tumor presence is crucial when choosing therapy. Clinical data demonstrate that let-7 can be used as a biomarker for rational precision medicine decisions, resulting in improved patient survival.
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Affiliation(s)
- Evgeny Chirshev
- Division of Anatomy, Department of Basic Sciences, Loma Linda University, Loma Linda, CA, USA
| | - Kerby C Oberg
- Division of Anatomy and Pediatric Pathology, Loma Linda University, Loma Linda, CA, USA
| | - Yevgeniya J Ioffe
- Gynecology and Obstetrics, School of Medicine, Loma Linda University, Loma Linda, CA, USA
| | - Juli J Unternaehrer
- Division of Biochemistry, Department of Basic Sciences, Loma Linda University, 11085 Campus Street, Mortensen Hall 219, Loma Linda, CA, 92354, USA.
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McDonald AC, Raman JD, Shen J, Liao J, Pandya B, Vira MA. Circulating microRNAs in plasma before and after radical prostatectomy. Urol Oncol 2019; 37:814.e1-814.e7. [PMID: 31421994 DOI: 10.1016/j.urolonc.2019.07.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 06/11/2019] [Accepted: 07/01/2019] [Indexed: 01/30/2023]
Abstract
PURPOSE MicroRNAs (miRNAs/miRs) as circulating biomarkers for prostate cancer have yet to be determined. We examined whether circulating miRNAs in plasma could be employed as biomarkers of disease among men treated for prostate cancer by radical prostatectomy (RP). METHODS The expression of 17 preselected circulating miRNAs associated with prostate cancer (miR-381, -34a, -365, -122, -375, -1255b, -34b, -450b-5p, -885-5p, -1260, -150, -378, -671-3p, -148a, and -224) or high-grade prostate cancer (miR-28 and -100) in plasma at prostate biopsy was examined in pre- and post-RP plasma of prostate cancer patients using real-time PCR and compared using Wilcoxon signed-ranked test. Wilcoxon rank sum test was used to compare the expression of miRNAs in pre-RP plasma between pathologic tumor stage (T2 vs. T3) and Gleason score (6-7 [3 + 4] vs. ≥ 7 [4 + 3]) groups. Partial correlation coefficient between the expression of miRNAs in pre-RP plasma and serum prostate-specific antigen (PSA) level at RP, adjusting for age, was calculated. RESULTS Twenty-nine men, aged 43 to 77 years, were included. Median follow-up time after RP was 55 days. There was no significant change in the expression of miRNAs in plasma from before to after RP. However, higher expression of miR-34a, -378, and 450b-5p in pre-RP plasma was observed among T3 compared to T2 patients (P values = 0.01). Overall, there were no statistically significant relationships observed between the expression of these circulating miRNAs and Gleason score and serum PSA at RP. CONCLUSIONS There was no significant change in the expression of circulating miRNAs in plasma from before to approximately 2 months after RP. This finding may be due to the lack of immediate effect RP may have on the expression of circulating miRNAs. However, higher expression of miR-34a, -378, and -450b-5p in plasma was found among patients with more advanced disease at RP. A longer follow-up time after RP is warranted to investigate RP's possible influence on circulating miRNAs among men treated for prostate cancer and to evaluate miRNAs' diagnostic potential for prostate cancer.
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Affiliation(s)
- Alicia C McDonald
- Department of Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, PA.
| | - Jay D Raman
- Division of Urology, Penn State Health Milton S. Hershey Medical Center, Hershey, PA
| | - Jing Shen
- Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY
| | - Jason Liao
- Department of Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, PA
| | - Bhavyata Pandya
- Department of Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, PA
| | - Manish A Vira
- Smith Institute for Urology, Zucker School of Medicine at Hofstra/Northwell, Northwell Cancer Institute, New Hyde Park, NY
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43
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Circulating microRNAs as potential diagnostic biomarkers and therapeutic targets in prostate cancer: Current status and future perspectives. J Cell Biochem 2019; 120:16316-16329. [DOI: 10.1002/jcb.29053] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2018] [Accepted: 02/04/2019] [Indexed: 12/19/2022]
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Lu YT, Delijani K, Mecum A, Goldkorn A. Current status of liquid biopsies for the detection and management of prostate cancer. Cancer Manag Res 2019; 11:5271-5291. [PMID: 31239778 PMCID: PMC6559244 DOI: 10.2147/cmar.s170380] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Accepted: 04/18/2019] [Indexed: 12/14/2022] Open
Abstract
In recent years, new therapeutic options have become available for prostate cancer (PC) patients, generating an urgent need for better biomarkers to guide the choice of therapy and monitor treatment response. Liquid biopsies, including circulating tumor cells (CTCs), circulating nucleic acids, and exosomes, have been developed as minimally invasive assays allowing oncologists to monitor PC patients with real-time cellular or molecular information. While CTC counts remain the most extensively validated prognostic biomarker to monitor treatment response, recent advances demonstrate that CTC morphology and androgen receptor characterization can provide additional information to guide the choice of treatment. Characterization of cell-free DNA (cfDNA) is another rapidly emerging field with novel technologies capable of monitoring the evolution of treatment relevant alterations such as those in DNA damage repair genes for poly (ADP-ribose) polymerase (PARP) inhibition. In addition, several new liquid biopsy fields are emerging, including the characterization of heterogeneity, CTC RNA sequencing, the culture and xenografting of CTCs, and the characterization of extracellular vesicles (EVs) and circulating microRNAs. This review describes the clinical utilization of liquid biopsies in the management of PC patients and emerging liquid biopsy technologies with the potential to advance personalized cancer therapy.
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Affiliation(s)
- Yi-Tsung Lu
- Division of Medical Oncology, Department of Medicine, Keck School of Medicine and Translational and Clinical Science Program, USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA
| | - Kevin Delijani
- Division of Medical Oncology, Department of Medicine, Keck School of Medicine and Translational and Clinical Science Program, USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA
| | - Andrew Mecum
- Division of Medical Oncology, Department of Medicine, Keck School of Medicine and Translational and Clinical Science Program, USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA
| | - Amir Goldkorn
- Division of Medical Oncology, Department of Medicine, Keck School of Medicine and Translational and Clinical Science Program, USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA
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45
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Hoey C, Ahmed M, Fotouhi Ghiam A, Vesprini D, Huang X, Commisso K, Commisso A, Ray J, Fokas E, Loblaw DA, He HH, Liu SK. Circulating miRNAs as non-invasive biomarkers to predict aggressive prostate cancer after radical prostatectomy. J Transl Med 2019; 17:173. [PMID: 31122242 PMCID: PMC6533745 DOI: 10.1186/s12967-019-1920-5] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Accepted: 05/15/2019] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Prostate cancer is an extremely heterogeneous disease. Despite being clinically similar, some tumours are more likely to recur after surgery compared to others. Distinguishing those that need adjuvant or salvage radiotherapy will improve patient outcomes. The goal of this study was to identify circulating microRNA that could independently predict prostate cancer patient risk stratification after radical prostatectomy. METHODS Seventy-eight prostate cancer patients were recruited at the Odette Cancer Centre in Sunnybrook Health Sciences Centre. All patients had previously undergone radical prostatectomy. Blood samples were collected simultaneously for PSA testing and miRNA analysis using NanoString nCounter technology. Of the 78 samples, 75 had acceptable miRNA quantity and quality. Patients were stratified into high- and low-risk categories based on Gleason score, pathological T stage, surgical margin status, and diagnostic PSA: patients with Gleason ≥ 8; pT3a and positive margin; pT3b and any margin; or diagnostic PSA > 20 µg/mL were classified as high-risk (n = 44) and all other patients were classified as low-risk (n = 31). RESULTS Using our patient dataset, we identified a four-miRNA signature (miR-17, miR-20a, miR-20b, miR-106a) that can distinguish high- and low-risk patients, in addition to their pathological tumour stage. High expression of these miRNAs is associated with shorter time to biochemical recurrence in the TCGA dataset. These miRNAs confer an aggressive phenotype upon overexpression in vitro. CONCLUSIONS This proof-of-principle report highlights the potential of circulating miRNAs to independently predict risk stratification of prostate cancer patients after radical prostatectomy.
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Affiliation(s)
- C Hoey
- Biological Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, Canada
| | - M Ahmed
- Princess Margaret Cancer Centre, niversity Health Network, Toronto, Canada
| | - A Fotouhi Ghiam
- Biological Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada
- Department of Radiation Oncology, Sunnybrook-Odette Cancer Centre, University of Toronto, Toronto, Canada
| | - D Vesprini
- Biological Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada
- Department of Radiation Oncology, Sunnybrook-Odette Cancer Centre, University of Toronto, Toronto, Canada
| | - X Huang
- Biological Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada
| | - K Commisso
- Biological Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada
| | - A Commisso
- Biological Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada
| | - J Ray
- Biological Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, Canada
| | - E Fokas
- Department of Radiotherapy and Oncology, Goethe-Universität Frankfurt am Main, Frankfurt, Germany
| | - D A Loblaw
- Biological Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada
- Department of Radiation Oncology, Sunnybrook-Odette Cancer Centre, University of Toronto, Toronto, Canada
| | - H H He
- Department of Medical Biophysics, University of Toronto, Toronto, Canada
- Princess Margaret Cancer Centre, niversity Health Network, Toronto, Canada
| | - S K Liu
- Biological Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada.
- Department of Medical Biophysics, University of Toronto, Toronto, Canada.
- Department of Radiation Oncology, Sunnybrook-Odette Cancer Centre, University of Toronto, Toronto, Canada.
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46
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Zedan AH, Hansen TF, Assenholt J, Madsen JS, Osther PJS. Circulating miRNAs in localized/locally advanced prostate cancer patients after radical prostatectomy and radiotherapy. Prostate 2019; 79:425-432. [PMID: 30537232 PMCID: PMC6587522 DOI: 10.1002/pros.23748] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Accepted: 11/08/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND Overtreatment is a well-known clinical challenge in local prostate cancer (PCa). Although risk assessment models have contributed to a better stratification of patients with local PCa, a tailored management is still in its infancy. Over the last few decades, microRNAs (miRNAs) have shown promising results as biomarkers in PCa. The aim of this study was to investigate circulating miRNAs after management of local PCa. METHODS The relative expression of four miRNAs (miRNA-21, -93, -125b, and miRNA-221) was assessed in plasma from 149 newly diagnosed patients with local or locally advanced PCa. Real-time polymerase chain reaction was used for analysis. A baseline sample at time of diagnosis and a follow-up sample after 6 months were assessed. The patients were grouped in an interventional cohort (radical prostatectomy, curative intent radiotherapy, or androgen-deprivation therapy alone) and an observational cohort (watchful waiting or active surveillance). RESULTS In the interventional cohort, levels of both miRNA-93 and miRNA-221 were significantly lower in the follow-up samples compared to baseline z = -2.738, P = 0.006, and z = -4.498, P < 0.001, respectively. The same observation was recorded for miRNA-125b in the observational cohort (z = -2.656, P = 0.008). Both miRNA-125b and miRNA-221 were correlated with risk assessment r = 0.23, P = 0.015, and r = 0.203, P = 0.016 respectively, while miRNA-93 showed tendency to significant correlation with the prostatectomy Gleason score (r = 0.276, P = 0.0576). CONCLUSIONS The current results indicate a possible role of miRNA-93 and miRNA-221 in disease monitoring in localized and locally advanced PCa. Larger studies are warranted to assess the clinical impact of these biomarkers.
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Affiliation(s)
- Ahmed H. Zedan
- Urological Research CentreDepartment of UrologyVejle HospitalVejleDenmark
- Department of OncologyVejle HospitalVejleDenmark
- Institute of Regional Health ResearchUniversity of Southern DenmarkVejleDenmark
| | - Torben F. Hansen
- Department of OncologyVejle HospitalVejleDenmark
- Institute of Regional Health ResearchUniversity of Southern DenmarkVejleDenmark
| | - Jannie Assenholt
- Department of Biochemistry and Clinical ImmunologyVejle HospitalVejleDenmark
| | - Jonna S. Madsen
- Institute of Regional Health ResearchUniversity of Southern DenmarkVejleDenmark
- Department of Biochemistry and Clinical ImmunologyVejle HospitalVejleDenmark
| | - Palle J. S. Osther
- Urological Research CentreDepartment of UrologyVejle HospitalVejleDenmark
- Institute of Regional Health ResearchUniversity of Southern DenmarkVejleDenmark
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47
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Hoey C, Liu SK. Circulating blood miRNAs for prostate cancer risk stratification: miRroring the underlying tumor biology with liquid biopsies. Res Rep Urol 2019; 11:29-42. [PMID: 30881943 PMCID: PMC6398395 DOI: 10.2147/rru.s165625] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Current risk stratification methods for prostate cancer – although they have seen marked improvements over the past decades – are far from perfect. Despite the significant utility of prostate-specific antigen as a biomarker to monitor for disease recurrence, it cannot predict which tumors will recur or recommend the best treatment for patients. Similarly, although biopsies are imperative for diagnosis and staging, they are saddled with limitations and risks. We must move toward a noninvasive biomarker that has predictive and prognostic efficacy. We therefore review the current literature on circulating miRNA biomarkers, apply their use to two significant clinical problems (ie, how limitations of prostate biopsies can impact diagnosis and treatment management, and the need to tailor treatment for a clinically heterogeneous disease), and evaluate how circulating miRNAs have inherent properties that make them ideal liquid biomarkers. We also outline current gaps in knowledge that must be addressed before they can be implemented into routine clinical practice. With further research on their function and validation of their biomarker utility in large prospective cohorts, circulating miRNAs will likely prove to be the liquid biopsies of tomorrow.
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Affiliation(s)
- Christianne Hoey
- Biological Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada, .,Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada,
| | - Stanley K Liu
- Biological Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada, .,Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada, .,Department of Radiation Oncology, University of Toronto, Toronto, ON M5S 3E2, Canada,
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48
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Zhan F, Shen J, Wang R, Wang L, Dai Y, Zhang Y, Huang X. Role of exosomal small RNA in prostate cancer metastasis. Cancer Manag Res 2018; 10:4029-4038. [PMID: 30319287 PMCID: PMC6167994 DOI: 10.2147/cmar.s170610] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Prostate cancer (PCa) is the second most common cancer in men worldwide. When the disease becomes metastatic, limited treatment strategies exist, and metastatic disease prognoses are difficult to predict. Recently, evidence has emerged, which indicates that small RNAs are detectable in patient fluids, and exosomal small RNA ectopic expression is correlated with the development, progression, and metastasis of human PCa; however, the role of small RNAs in PCa is only partially understood. In this review, we discuss the research status regarding circulating exosomal small RNAs and applications using these small RNAs in PCa particularly looking at metastatic disease. Exosomal small RNAs could be used as potential biomarkers for the early diagnosis, micrometastasis detection, and prognosis of PCa.
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Affiliation(s)
- Fei Zhan
- Department of Gastrointestinal Medical Oncology, Tumor Hospital of Harbin Medical University, Harbin 150081, China,
| | - Jingling Shen
- Department of Histology and Embryology, Harbin Medical University, Harbin 150081, China
| | - Ruitao Wang
- Department of Internal Medicine, Tumor Hospital of Harbin Medical University, Harbin 150081, China
| | - Liang Wang
- Department of Pathology and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI, 53226, USA
| | - Yao Dai
- Department of Radiation Oncology, University of Florida, Gainesville, FL, 32610, USA
| | - Yanqiao Zhang
- Department of Gastrointestinal Medical Oncology, Tumor Hospital of Harbin Medical University, Harbin 150081, China,
| | - Xiaoyi Huang
- Biotherapy Center, Tumor Hospital of Harbin Medical University, Harbin 150081, China,
- Center of Translational Medicine, Harbin Medical University, Harbin 150086, China,
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49
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Porzycki P, Ciszkowicz E, Semik M, Tyrka M. Combination of three miRNA (miR-141, miR-21, and miR-375) as potential diagnostic tool for prostate cancer recognition. Int Urol Nephrol 2018; 50:1619-1626. [PMID: 30014459 PMCID: PMC6133127 DOI: 10.1007/s11255-018-1938-2] [Citation(s) in RCA: 96] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2018] [Accepted: 07/11/2018] [Indexed: 01/11/2023]
Abstract
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.
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Affiliation(s)
- Paweł Porzycki
- Department of Urology, Municipal Hospital Rzeszow, 4 Rycerska Street, 35-241, Rzeszow, Poland
| | - Ewa Ciszkowicz
- Department of Biotechnology and Bioinformatics, Faculty of Chemistry, Rzeszow University of Technology, 6 Powstańców Warszawy Street, 35-503, Rzeszow, Poland.
| | - Małgorzata Semik
- Department of Biotechnology and Bioinformatics, Faculty of Chemistry, Rzeszow University of Technology, 6 Powstańców Warszawy Street, 35-503, Rzeszow, Poland
| | - Mirosław Tyrka
- Department of Biotechnology and Bioinformatics, Faculty of Chemistry, Rzeszow University of Technology, 6 Powstańców Warszawy Street, 35-503, Rzeszow, Poland
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Liu X, Yao B, Wu Z. miRNA-199a-5p suppresses proliferation and invasion by directly targeting NF-κB1 in human ovarian cancer cells. Oncol Lett 2018; 16:4543-4550. [PMID: 30214589 DOI: 10.3892/ol.2018.9170] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2016] [Accepted: 03/28/2018] [Indexed: 12/12/2022] Open
Abstract
The aberrant expression of microRNA (miRNA)-199a-5p has been frequently reported in a number of cancer types, but to the best of our knowledge, this has not been reported in ovarian cancer (OC). The role and the molecular mechanism of miR-199a-5p in OC have not been reported. Therefore, the present study investigated the effects of miR-199a-5p overexpression on the proliferation and invasion of OC cells. The level of miR-199a-5p in OC cell lines was determined by reverse transcription-quantitative polymerase chain reaction. The miR-199a-5p mimic was transiently transfected into OC cells using Lipofectamine™ 2000 reagent. Subsequently, the BrdU-ELISA results indicated that the exogenous expression of miR-199a-5p inhibited cell proliferation. In addition, miR-199a-5p overexpression was able to inhibit the invasion of HO-8910 and ES-2 cells. RT-qPCR was performed to determine the expression of matrix metalloproteinase (MMP)-2 and -9 in OC cells. NF-κB1 expression was reduced by upregulation of miR-199a-5p. Bioinformatics analysis predicted that NF-κB1 was a potential target of miR-199a-5p. Luciferase reporter assay further confirmed that miR-199a-5p was able to directly target the 3'UTR of NF-κB1. In conclusion, miRNA-199a-5p may suppress the proliferation and invasion of human ovarian cancer cells by directly targeting NF-κB1.
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Affiliation(s)
- Xiaoxiao Liu
- Department of Internal Medicine-Oncology, Xinchang People's Hospital of Zhejiang, Shaoxing, Zhejiang 312500, P.R. China
| | - Baofeng Yao
- Department of Intensive Care Unit, Putuo Hospital of Zhejiang, Zhoushan, Zhejiang 316100, P.R. China
| | - Zhiming Wu
- Department of General Surgery, Shaoxing Hospital of China Medical University, Shaoxing, Zhejiang 312030, P.R. China
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