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1
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Hamid Y, Rabbani RD, Afsara R, Nowrin S, Ghose A, Papadopoulos V, Sirlantzis K, Ovsepian SV, Boussios S. Exosomal Liquid Biopsy in Prostate Cancer: A Systematic Review of Biomarkers for Diagnosis, Prognosis, and Treatment Response. Int J Mol Sci 2025; 26:802. [PMID: 39859516 PMCID: PMC11765602 DOI: 10.3390/ijms26020802] [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: 12/07/2024] [Revised: 01/15/2025] [Accepted: 01/17/2025] [Indexed: 01/27/2025] Open
Abstract
Prostate cancer, a leading cause of cancer-related mortality among men, often presents challenges in accurate diagnosis and effective monitoring. This systematic review explores the potential of exosomal biomolecules as noninvasive biomarkers for the diagnosis, prognosis, and treatment response of prostate cancer. A thorough systematic literature search through online public databases (Medline via PubMed, Scopus, and Web of science) using structured search terms and screening using predefined eligibility criteria resulted in 137 studies that we analyzed in this systematic review. We evaluated the findings from these clinical studies, revealing that the load of exosomes in the blood and urine of prostate cancer patients, which includes microRNAs (miRNAs), proteins, and lipids, demonstrates disease-specific changes. It also shows that some exosomal markers can differentiate between malignant and benign hyperplasia of the prostate, predict disease aggressiveness, and monitor treatment efficacy. Notably, miRNA emerged as the most frequently studied biomolecule, demonstrating superior diagnostic potential compared to traditional methods like prostate-specific antigen (PSA) testing. The analysis also highlights the pressing need for a standardised analytic approach through multi-centre studies to validate the full potential of exosomal biomarkers for the diagnosis and monitoring of prostate cancer.
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Affiliation(s)
- Yameen Hamid
- The University of Edinburgh, Edinburgh EH8 9YL, UK;
- Department of Acute Medicine, Medway NHS Foundation Trust, Gillingham ME7 5NY, UK
| | - Rukhshana Dina Rabbani
- Department of Medical Oncology, Medway NHS Foundation Trust, Gillingham ME7 5NY, UK; (R.D.R.); (A.G.)
| | - Rakkan Afsara
- Department of Medical Oncology, Evercare Hospital, Dhaka 1205, Bangladesh;
| | - Samarea Nowrin
- Department of Clinical Oncology, Maidstone and Tunbridge Wells NHS Trust, Maidstone ME16 9QQ, UK;
| | - Aruni Ghose
- Department of Medical Oncology, Medway NHS Foundation Trust, Gillingham ME7 5NY, UK; (R.D.R.); (A.G.)
| | | | - Konstantinos Sirlantzis
- School of Engineering, Technology and Design, Canterbury Christ Church University, Canterbury CT1 1QU, UK;
| | - Saak V. Ovsepian
- Faculty of Engineering and Science, University of Greenwich London, Chatham Maritime, Kent ME4 4TB, UK;
- Faculty of Medicine, Tbilisi State University, Tbilisi 0177, Georgia
| | - Stergios Boussios
- Department of Medical Oncology, Medway NHS Foundation Trust, Gillingham ME7 5NY, UK; (R.D.R.); (A.G.)
- Faculty of Medicine, Health, and Social Care, Canterbury Christ Church University, Canterbury CT2 7PB, UK
- School of Cancer and Pharmaceutical Sciences, Faculty of Life Sciences and Medicine, King’s College London, Strand, London WC2R 2LS, UK
- Kent and Medway Medical School, University of Kent, Canterbury CT2 7LX, UK
- AELIA Organisation, 9th km Thessaloniki—Thermi, 57001 Thessaloniki, Greece
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2
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Nobrega M, Bisarro Dos Reis M, Ferreira de Souza M, Hugo Furini H, Costa Brandão Berti F, Larissa Melo Souza I, Mingorance Carvalho T, Zanata SM, Emilio Fuganti P, Malheiros D, Maria de Souza Fonseca Ribeiro E, Mara de Syllos Cólus I. Comparative analysis of extracellular vesicles miRNAs (EV-miRNAs) and cell-free microRNAs (cf-miRNAs) reveals that EV-miRNAs are more promising as diagnostic and prognostic biomarkers for prostate cancer. Gene 2024:149186. [PMID: 39708932 DOI: 10.1016/j.gene.2024.149186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 12/10/2024] [Accepted: 12/17/2024] [Indexed: 12/23/2024]
Abstract
MicroRNAs can be found intracellularly incorporated into extracellular vesicles (EV-miRNAs) or extracellularly as cell-free miRNAs (cf-miRNAs). This study aimed to compare the diagnostic and prognostic potential of four miRNAs with recognized roles in prostate cancer as cf-miRNAs and EV-miRNAs, obtained from liquid biopsies (LB). Total RNA was isolated from whole plasma and plasma EVs from 15 controls (CTR) and 30 patients (20 with localized prostate cancer (PCa), 10 with metastatic prostate cancer (mPCa)). The miRNAs were quantified by RT-qPCR and the relative expression of these miRNAs was compared between the three groups, and their associations with clinicopathological parameters were assessed. Receiver operating characteristic (ROC) curves were performed to evaluate the diagnostic potential of the miRNAs in discriminating different groups. Overall, EV-miRNAs showed higher expression compared to cf-miRNAs. All EV-miRNAs analyzed showed diagnostic potential with an area under the curve (AUC) above 0.744. EV-miR-21-5p, EV-miR-375-3p, and EV-miR-1290-3p were overexpressed in PCa and mPCa compared to CTR, while EV-miR-200c-3p was overexpressed only in mPCa in comparison to CTR. Remarkably, EV-miR-375-3p and EV-miR-1290-3p could differentiate mPCa with ISUP ≥ 3, demonstrating their prognostic potential. In addition, EV-miR-1290-3p and EV-4-miR-panel detected patients with PSA > 10 ng/mL. Cf-miRNAs performed lower than EV-miRNAs, which can be explained by the greater stability and specificity of EV-miRNAs, making them superior to cf-miRNA. The results show that LB, a non-invasive strategy, is clinically feasible to identify EV-miRNAs as biomarkers for PCa and may provide additional information for assessing PCa risk stratification.
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Affiliation(s)
- Monyse Nobrega
- Department of General Biology, State University of Londrina, Londrina, Paraná, Brazil
| | | | | | - Hector Hugo Furini
- Department of General Biology, State University of Londrina, Londrina, Paraná, Brazil
| | - Fernanda Costa Brandão Berti
- Postgraduate Program in Genetics, Department of Genetics, Federal University of Paraná, Curitiba, Paraná, Brazil
| | - Ingrid Larissa Melo Souza
- Department of Cell and Molecular Biology, Federal University of Paraná, Curitiba, Paraná, Brazil; Laboratory for Applied Science and Technology in Health (LACTAS), Carlos Chagas Institute, FIOCRUZ/PR, Curitiba, Paraná, Brazil
| | - Tamyres Mingorance Carvalho
- Postgraduate Program in Genetics, Department of Genetics, Federal University of Paraná, Curitiba, Paraná, Brazil
| | - Silvio M Zanata
- Department of Cell and Molecular Biology, Federal University of Paraná, Curitiba, Paraná, Brazil.
| | | | - Danielle Malheiros
- Postgraduate Program in Genetics, Department of Genetics, Federal University of Paraná, Curitiba, Paraná, Brazil.
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3
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Luo X, Wen W. MicroRNA in prostate cancer: from biogenesis to applicative potential. BMC Urol 2024; 24:244. [PMID: 39506720 PMCID: PMC11539483 DOI: 10.1186/s12894-024-01634-1] [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: 08/12/2024] [Accepted: 10/21/2024] [Indexed: 11/08/2024] Open
Abstract
Prostate cancer is the most common solid malignant tumor in men, characterized by high morbidity and mortality. While current screening tools, such as prostate-specific antigen (PSA) testing and digital rectal examination, are available for early detection of prostate cancer, their sensitivity and specificity are limited. Tissue puncture biopsy, although capable of offering a definitive diagnosis, has poor positive predictive rates and burdens the patient more. Therefore, more reliable molecular diagnostic tools for prostate cancer urgently need to be developed. In recent years, microRNAs (miRNAs) have attracted much attention in prostate cancer research. miRNAs are extensively engaged in biological processes such as cell proliferation, differentiation, apoptosis, migration, and invasion by modulating gene expression post-transcriptionally. Dysregulation of miRNA expression in cancer is considered a critical factor in tumorigenesis and progression. This review first briefly introduces the biogenesis of miRNAs and their functions in cancer, then focuses on tumor-promoting miRNAs and tumor-suppressor miRNAs in prostate cancer. Finally, the potential application of miRNAs as multifunctional tools for cancer diagnosis, prognostic assessment, and therapy is discussed in detail. The concluding section summarizes the major points of the review and the challenges ahead.
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Affiliation(s)
- Xu Luo
- Department of Urology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, 610041, P.R. China
| | - Wei Wen
- Department of Urology, West China Tianfu Hospital, Sichuan University, Chengdu, 610213, P.R. China.
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4
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Wei Y, Hu Y, Zhang C, Liu R, Lv Y. Single Particle Analysis-Enhanced DNA Walking Machine for Sensitive miRNA Detection. Anal Chem 2024; 96:11566-11571. [PMID: 38940610 DOI: 10.1021/acs.analchem.4c02404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/29/2024]
Abstract
DNA walking machines have achieved significant breakthroughs in areas such as biosensing, bioimaging, and early cancer diagnosis, facilitated by the self-assembly of DNA or its combination with other materials, such as magnetic beads and metal nanoparticles. However, current DNA walking machine strategies are constantly challenged by inadequate analytical sensitivity, while sophisticated signal amplification procedures are often indispensable. Single-particle inductively coupled plasma mass spectrometry (SP-ICPMS) provides superior sensitivity and can effectively discriminate between background noise and detected signals due to the large number of metal atoms in a nanoparticle and the concentrating effect of single nanoparticle detection. In this study, we present a novel approach utilizing single nanoparticle counting and duplex-specific nuclease (DSN)-assisted signal amplification to construct a 3D DNA walking machine for detecting the aggressive prostate cancer (PCa) biomarker miRNA-200c. The proposed strategy showed an improvement in sensitivity with a detection limit (LOD) of 0.93 pM (28 amol) and was successfully applied in human serum samples. To the best of our knowledge, this is the first report of the DNA walking machine with single nanoparticle counting study.
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Affiliation(s)
- Yanxue Wei
- Analytical & Testing Center, Sichuan University, Chengdu 610064, PR China
| | - Yueli Hu
- Key Laboratory of Green Chemistry & Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu, Sichuan 610064, China
| | - Chengchao Zhang
- Key Laboratory of Green Chemistry & Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu, Sichuan 610064, China
| | - Rui Liu
- Key Laboratory of Green Chemistry & Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu, Sichuan 610064, China
| | - Yi Lv
- Analytical & Testing Center, Sichuan University, Chengdu 610064, PR China
- Key Laboratory of Green Chemistry & Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu, Sichuan 610064, China
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Wang F, Zhou C, Zhu Y, Keshavarzi M. The microRNA Let-7 and its exosomal form: Epigenetic regulators of gynecological cancers. Cell Biol Toxicol 2024; 40:42. [PMID: 38836981 PMCID: PMC11153289 DOI: 10.1007/s10565-024-09884-3] [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: 01/31/2024] [Accepted: 05/15/2024] [Indexed: 06/06/2024]
Abstract
Many types of gynecological cancer (GC) are often silent until they reach an advanced stage, and are therefore often diagnosed too late for effective treatment. Hence, there is a real need for more efficient diagnosis and treatment for patients with GC. During recent years, researchers have increasingly studied the impact of microRNAs cancer development, leading to a number of applications in detection and treatment. MicroRNAs are a particular group of tiny RNA molecules that regulate regular gene expression by affecting the translation process. The downregulation of numerous miRNAs has been observed in human malignancies. Let-7 is an example of a miRNA that controls cellular processes as well as signaling cascades to affect post-transcriptional gene expression. Recent research supports the hypothesis that enhancing let-7 expression in those cancers where it is downregulated may be a potential treatment option. Exosomes are tiny vesicles that move through body fluids and can include components like miRNAs (including let-7) that are important for communication between cells. Studies proved that exosomes are able to enhance tumor growth, angiogenesis, chemoresistance, metastasis, and immune evasion, thus suggesting their importance in GC management.
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Affiliation(s)
- Fei Wang
- Haiyan People's Hospital, Zhejiang Province, Jiaxing, 314300, Zhejiang, China
| | - Chundi Zhou
- Haiyan People's Hospital, Zhejiang Province, Jiaxing, 314300, Zhejiang, China
| | - Yanping Zhu
- Haiyan People's Hospital, Zhejiang Province, Jiaxing, 314300, Zhejiang, China.
| | - Maryam Keshavarzi
- School of Medicine, Tehran University of Medical Sciences, Tehran, Tehran, Iran.
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Kalele K, Nyahatkar S, Mirgh D, Muthuswamy R, Adhikari MD, Anand K. Exosomes: A Cutting-Edge Theranostics Tool for Oral Cancer. ACS APPLIED BIO MATERIALS 2024; 7:1400-1415. [PMID: 38394624 DOI: 10.1021/acsabm.3c01243] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/25/2024]
Abstract
Exosomes are a subpopulation of extracellular vesicles (EVs) secreted by cells. In cancer, they are key cellular messengers during cancer development and progression. Tumor-derived exosomes (TEXs) promote cancer progression. In oral cancer, the major complication is oral squamous cell carcinoma (OSCC). Exosomes show strong participation in several OSCC-related activities such as uncontrolled cell growth, immune suppression, angiogenesis, metastasis, and drug and therapeutic resistance. It is also a potential biomarker source for oral cancer. Some therapeutic exosome sources such as stem cells, plants (it is more effective compared to others), and engineered exosomes reduce oral cancer development. This therapeutic approach is effective because of its specificity, biocompatibility, and cell-free therapy (it reduced side effects in cancer treatment). This article highlights exosome-based theranostics signatures in oral cancer, clinical trials, challenges of exosome-based oral cancer research, and future improvements. In the future, exosomes may become an effective and affordable solution for oral cancer.
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Affiliation(s)
- Ketki Kalele
- Neuron Institute of Applied Research, Rajapeth-Irwin Square Flyover, Amravati, Maharashtra 444601, India
| | - Sidhanti Nyahatkar
- VYWS Dental College & Hospital, WQMV+7X6, Tapovan-Wadali Road, Camp Rd, SRPF Colony, Amravati, Maharashtra 444602, India
| | - Divya Mirgh
- Department of Infectious Diseases, Vaccine and Immunotherapy Center, Massachusetts General Hospital, Boston, Massachusetts 02114, United States
| | - Raman Muthuswamy
- Center for Global Health Research, Saveetha Medical College & Hospitals, Saveetha Institute of Medical and Technical Sciences, Chennai 602105, Tamil Nadu, India
| | - Manab Deb Adhikari
- Department of Biotechnology, University of North Bengal, Darjeeling, West Bengal 734013, India
| | - Krishnan Anand
- Department of Chemical Pathology, School of Pathology, Faculty of Health Sciences, University of the Free State, Bloemfontein 9300, South Africa
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7
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Nemeth K, Bayraktar R, Ferracin M, Calin GA. Non-coding RNAs in disease: from mechanisms to therapeutics. Nat Rev Genet 2024; 25:211-232. [PMID: 37968332 DOI: 10.1038/s41576-023-00662-1] [Citation(s) in RCA: 233] [Impact Index Per Article: 233.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/19/2023] [Indexed: 11/17/2023]
Abstract
Non-coding RNAs (ncRNAs) are a heterogeneous group of transcripts that, by definition, are not translated into proteins. Since their discovery, ncRNAs have emerged as important regulators of multiple biological functions across a range of cell types and tissues, and their dysregulation has been implicated in disease. Notably, much research has focused on the link between microRNAs (miRNAs) and human cancers, although other ncRNAs, such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), are also emerging as relevant contributors to human disease. In this Review, we summarize our current understanding of the roles of miRNAs, lncRNAs and circRNAs in cancer and other major human diseases, notably cardiovascular, neurological and infectious diseases. Further, we discuss the potential use of ncRNAs as biomarkers of disease and as therapeutic targets.
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Affiliation(s)
- Kinga Nemeth
- Translational Molecular Pathology Department, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Recep Bayraktar
- Translational Molecular Pathology Department, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Manuela Ferracin
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
| | - George A Calin
- Translational Molecular Pathology Department, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- The RNA Interference and Non-coding RNA Center, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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8
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Tavares I, Morais M, Dias F, Medeiros R, Teixeira AL. Deregulated miRNAs in enzalutamide resistant prostate cancer: A comprehensive review of key molecular alterations and clinical outcomes. Biochim Biophys Acta Rev Cancer 2024; 1879:189067. [PMID: 38160898 DOI: 10.1016/j.bbcan.2023.189067] [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: 06/02/2023] [Revised: 12/21/2023] [Accepted: 12/23/2023] [Indexed: 01/03/2024]
Abstract
Prostate cancer (PC) is the second most frequently diagnosed cancer and the fifth leading cause of cancer-related deaths in male population worldwide. Since the growth and progression of PC highly depend on the androgen pathway, androgen deprivation therapy (ADT) is the mainstay of systemic treatment. Enzalutamide is a second-generation antiandrogen, which is widely used for the treatment of advanced and metastatic PC. However, treatment failure and disease progression, caused by the emergence of enzalutamide resistant phenotypes, remains an important clinical challenge. MicroRNAs (miRNAs) are key regulators of gene expression and have recently emerged as potential biomarkers for being stable and easily analysed in several biological fluids. Several miRNAs that exhibit dysregulated expression patterns in enzalutamide-resistant PC have recently been identified, including miRNAs that modulate critical signalling pathways and genes involved in PC growth, survival and in the acquisition of enzalutamide phenotype. The understanding of molecular mechanisms by which miRNAs promote the development of enzalutamide resistance can provide valuable insights into the complex interplay between miRNAs, gene regulation, and treatment response in PC. Moreover, these miRNAs could serve as valuable tools for monitoring treatment response and disease progression during enzalutamide administration. This review summarises the miRNAs associated with enzalutamide resistance in PC already described in the literature, focusing on their biological roles and on their potential as biomarkers.
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Affiliation(s)
- Inês Tavares
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC) Raquel Seruca, Porto, Portugal; ICBAS School of Medicine and Biomedical Sciences, University of Porto (UP), Porto, Portugal
| | - Mariana Morais
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC) Raquel Seruca, Porto, Portugal; ICBAS School of Medicine and Biomedical Sciences, University of Porto (UP), Porto, Portugal
| | - Francisca Dias
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC) Raquel Seruca, Porto, Portugal
| | - Rui Medeiros
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC) Raquel Seruca, Porto, Portugal; ICBAS School of Medicine and Biomedical Sciences, University of Porto (UP), Porto, Portugal; Faculty of Medicine, University of Porto (FMUP), Porto, Portugal; Biomedical Reasearch Center, Faculty of Health Sciences, Fernando Pessoa University (UFP), Porto, Portugal; Research Department, LPCC- Portuguese League Against Cancer (NRNorte), Porto, Portugal
| | - Ana Luísa Teixeira
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC) Raquel Seruca, Porto, Portugal.
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Perrapato SD, Farina NH, Berg AN, Wallace HJ, Ades S, Ahern TP, Stein JL, Stein GS, Lian JB. A MicroRNA Approach to Evaluating Elevated Prostate Cancer Risk in Cancer-Free Men. Crit Rev Eukaryot Gene Expr 2024; 34:61-69. [PMID: 38912963 DOI: 10.1615/critreveukaryotgeneexpr.2024053672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/25/2024]
Abstract
Objective criteria are required for prostate cancer (PCa) risk assessment, treatment decisions, evaluation of therapy, and initial indications of recurrence. Circulating microRNAs were utilized as biomarkers to distinguish PCa patients from cancer-free subjects or those encountering benign prostate hyperplasia. A panel of 60 microRNAs was developed with established roles in PCa initiation, progression, metastasis, and recurrence. Utilizing the FirePlex® platform for microRNA analysis, we demonstrated the efficacy and reproducibility of a rapid, high-throughput, serum-based assay for PCa biomarkers that circumvents the requirement for extraction and fractionation of patient specimens supporting feasibility for expanded clinical research and diagnostic applications.
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Affiliation(s)
| | - Nicholas H Farina
- University of Vermont Cancer Center, Larner College of Medicine, University of Vermont, Burlington, Vermont; Department of Biochemistry, Larner College of Medicine, University of Vermont, Burlington, Vermont; Department of Surgery, Larner College of Medicine, University of Vermont Medical Center, Burlington, Vermont
| | - Adrian N Berg
- Department of Surgery, Larner College of Medicine, University of Vermont Medical Center, Burlington, Vermont
| | - H James Wallace
- University of Vermont Cancer Center, Larner College of Medicine, University of Vermont, Burlington, Vermont; Division of Radiation Oncology, Larner College of Medicine, University of Vermont, Burlington, Vermont
| | - Steven Ades
- University of Vermont Cancer Center, Larner College of Medicine, University of Vermont, Burlington, Vermont; Division of Hematology and Oncology, Larner College of Medicine, University of Vermont, Burlington, Vermont
| | | | - Janet L Stein
- Department of Biochemistry, University of Vermont Larner College of Medicine, Burlington, VT 05405; University of Vermont Cancer Center, University of Vermont Larner College of Medicine, Burlington, VT 05405
| | - Gary S Stein
- Department of Biochemistry, University of Vermont Larner College of Medicine, Burlington, VT 05405; University of Vermont Cancer Center, University of Vermont Larner College of Medicine, Burlington, VT 05405
| | - Jane B Lian
- Department of Biochemistry, University of Vermont Larner College of Medicine, Burlington, VT 05405; University of Vermont Cancer Center, University of Vermont Larner College of Medicine, Burlington, VT 05405
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10
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Zhou X, Liu M, Sun L, Cao Y, Tan S, Luo G, Liu T, Yao Y, Xiao W, Wan Z, Tang J. Circulating small extracellular vesicles microRNAs plus CA-125 for treatment stratification in advanced ovarian cancer. J Transl Med 2023; 21:927. [PMID: 38129848 PMCID: PMC10740240 DOI: 10.1186/s12967-023-04774-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Accepted: 11/28/2023] [Indexed: 12/23/2023] Open
Abstract
BACKGROUND No residual disease (R0 resection) after debulking surgery is the most critical independent prognostic factor for advanced ovarian cancer (AOC). There is an unmet clinical need for selecting primary or interval debulking surgery in AOC patients using existing prediction models. METHODS RNA sequencing of circulating small extracellular vesicles (sEVs) was used to discover the differential expression microRNAs (DEMs) profile between any residual disease (R0, n = 17) and no residual disease (non-R0, n = 20) in AOC patients. We further analyzed plasma samples of AOC patients collected before surgery or neoadjuvant chemotherapy via TaqMan qRT-PCR. The combined risk model of residual disease was developed by logistic regression analysis based on the discovery-validation sets. RESULTS Using a comprehensive plasma small extracellular vesicles (sEVs) microRNAs (miRNAs) profile in AOC, we identified and optimized a risk prediction model consisting of plasma sEVs-derived 4-miRNA and CA-125 with better performance in predicting R0 resection. Based on 360 clinical human samples, this model was constructed using least absolute shrinkage and selection operator (LASSO) and logistic regression analysis, and it has favorable calibration and discrimination ability (AUC:0.903; sensitivity:0.897; specificity:0.910; PPV:0.926; NPV:0.871). The quantitative evaluation of Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI) suggested that the additional predictive power of the combined model was significantly improved contrasted with CA-125 or 4-miRNA alone (NRI = 0.471, IDI = 0.538, p < 0.001; NRI = 0.122, IDI = 0.185, p < 0.01). CONCLUSION Overall, we established a reliable, non-invasive, and objective detection method composed of circulating tumor-derived sEVs 4-miRNA plus CA-125 to preoperatively anticipate the high-risk AOC patients of residual disease to optimize clinical therapy.
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Affiliation(s)
- Xiaofang Zhou
- Department of Gynecologic Oncology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, People's Republic of China
- Department of Oncology, Xiangya Cancer Center, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China
| | - Mu Liu
- Department of Gynecologic Oncology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, People's Republic of China
| | - Lijuan Sun
- Department of Gynecology and Obstetrics, The Central Hospital of Shaoyang, Shaoyang, 422000, People's Republic of China
| | - Yumei Cao
- Department of Gynecology and Obstetrics, The Central Hospital of Shaoyang, Shaoyang, 422000, People's Republic of China
| | - Shanmei Tan
- Department of Gynecology and Obstetrics, The First People's Hospital of Huaihua, The Affiliated Huaihua Hospital of University of South China, Huaihua, 418000, People's Republic of China
| | - Guangxia Luo
- Department of Gynecology and Obstetrics, The First People's Hospital of Huaihua, The Affiliated Huaihua Hospital of University of South China, Huaihua, 418000, People's Republic of China
| | - Tingting Liu
- Department of Gynecology and Obstetrics, The First People's Hospital of Changde, Changde, 415000, People's Republic of China
| | - Ying Yao
- Department of Gynecology and Obstetrics, The First People's Hospital of Yueyang, Yueyang, 414000, People's Republic of China
| | - Wangli Xiao
- Department of Gynecology and Obstetrics, The First People's Hospital of Yueyang, Yueyang, 414000, People's Republic of China
| | - Ziqing Wan
- Department of Gynecologic Oncology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, People's Republic of China
| | - Jie Tang
- Department of Gynecologic Oncology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, People's Republic of China.
- Department of Gynecologic Oncology, Hunan Gynecologic Cancer Research Center, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Address: 283 Tongzipo Road, Yuelu District, Changsha, 410013, People's Republic of China.
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11
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Alahdal M, Perera RA, Moschovas MC, Patel V, Perera RJ. Current advances of liquid biopsies in prostate cancer: Molecular biomarkers. Mol Ther Oncolytics 2023; 30:27-38. [PMID: 37575217 PMCID: PMC10415624 DOI: 10.1016/j.omto.2023.07.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/15/2023] Open
Abstract
Prostate cancer (PCa) incidence is increasing and endangers men's lives. Early detection of PCa could improve overall survival (OS) by preventing metastasis. The prostate-specific antigen (PSA) test is a popular screening method. Several advisory groups, however, warn against using the PSA test due to its high false positive rate, unsupported outcome, and limited benefit. The number of disease-related biopsies performed annually far outweighs the number of diagnoses. Thus, there is an urgent need to develop accurate diagnostic biomarkers to detect PCa and distinguish between aggressive and indolent cancers. Recently, non-coding RNA (ncRNA), circulating tumor DNA (ctDNA)/ctRNA, exosomes, and metabolomic biomarkers in the liquid biopsies (LBs) of patients with PCa showed significant differences and clinical benefits in diagnosis, prognosis, and monitoring response to therapy. The analysis of urinary exosomal ncRNA presented a substantial correlation among Exos-miR-375 downregulation, clinical T stage, and bone metastases of PCa. Furthermore, the expression of miR-532-5p in urine samples was a vital predictive biomarker of PCa progression. Thus, this review focuses on promising molecular and metabolomic biomarkers in LBs from patients with PCa. We thoroughly addressed the most recent clinical findings of LB biomarker use in diagnosing and monitoring PCa in early and advanced stages.
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Affiliation(s)
- Murad Alahdal
- Johns Hopkins All Children’s Hospital, 600 5th St. South, St. Petersburg, FL 33701, USA
- Department of Oncology, Sydney Kimmel Cancer Center, School of Medicine, Johns Hopkins University, 401 N. Broadway, Baltimore, MD 21287, USA
| | - Roshane A. Perera
- AdventHealth Celebration, 380 Celebration Place, Celebration, FL 34747, USA
| | | | - Vipul Patel
- AdventHealth Celebration, 380 Celebration Place, Celebration, FL 34747, USA
| | - Ranjan J. Perera
- Johns Hopkins All Children’s Hospital, 600 5th St. South, St. Petersburg, FL 33701, USA
- Department of Oncology, Sydney Kimmel Cancer Center, School of Medicine, Johns Hopkins University, 401 N. Broadway, Baltimore, MD 21287, USA
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12
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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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13
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Lyu F, Gao X, Ma M, Xie M, Shang S, Ren X, Liu M, Chen J. Crafting a Personalized Prognostic Model for Malignant Prostate Cancer Patients Using Risk Gene Signatures Discovered through TCGA-PRAD Mining, Machine Learning, and Single-Cell RNA-Sequencing. Diagnostics (Basel) 2023; 13:1997. [PMID: 37370891 DOI: 10.3390/diagnostics13121997] [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: 04/09/2023] [Revised: 05/24/2023] [Accepted: 06/02/2023] [Indexed: 06/29/2023] Open
Abstract
BACKGROUND Prostate cancer is a significant clinical issue, particularly for high Gleason score (GS) malignancy patients. Our study aimed to engineer and validate a risk model based on the profiles of high-GS PCa patients for early identification and the prediction of prognosis. METHODS We conducted differential gene expression analysis on patient samples from The Cancer Genome Atlas (TCGA) and enriched our understanding of gene functions. Using the least absolute selection and shrinkage operator (LASSO) regression, we established a risk model and validated it using an independent dataset from the International Cancer Genome Consortium (ICGC). Clinical variables were incorporated into a nomogram to predict overall survival (OS), and machine learning was used to explore the risk factor characteristics' impact on PCa prognosis. Our prognostic model was confirmed using various databases, including single-cell RNA-sequencing datasets (scRNA-seq), the Cancer Cell Line Encyclopedia (CCLE), PCa cell lines, and tumor tissues. RESULTS We identified 83 differentially expressed genes (DEGs). Furthermore, WASIR1, KRTAP5-1, TLX1, KIF4A, and IQGAP3 were determined to be significant risk factors for OS and progression-free survival (PFS). Based on these five risk factors, we developed a risk model and nomogram for predicting OS and PFS, with a C-index of 0.823 (95% CI, 0.766-0.881) and a 10-year area under the curve (AUC) value of 0.788 (95% CI, 0.633-0.943). Additionally, the 3-year AUC was 0.759 when validating using ICGC. KRTAP5-1 and WASIR1 were found to be the most influential prognosis factors when using the optimized machine learning model. Finally, the established model was interrelated with immune cell infiltration, and the signals were found to be differentially expressed in PCa cells when using scRNA-seq datasets and tissues. CONCLUSIONS We engineered an original and novel prognostic model based on five gene signatures through TCGA and machine learning, providing new insights into the risk of scarification and survival prediction for PCa patients in clinical practice.
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Affiliation(s)
- Feng Lyu
- Department of Radiation Oncology, Peking University First Hospital, Beijing 100034, China
| | - Xianshu Gao
- Department of Radiation Oncology, Peking University First Hospital, Beijing 100034, China
| | - Mingwei Ma
- Department of Radiation Oncology, Peking University First Hospital, Beijing 100034, China
| | - Mu Xie
- Department of Radiation Oncology, Peking University First Hospital, Beijing 100034, China
| | - Shiyu Shang
- Department of Radiation Oncology, Peking University First Hospital, Beijing 100034, China
- First Clinical Medical School, Hebei North University, Zhangjiakou 075000, China
| | - Xueying Ren
- Department of Radiation Oncology, Peking University First Hospital, Beijing 100034, China
| | - Mingzhu Liu
- Department of Radiation Oncology, Peking University First Hospital, Beijing 100034, China
| | - Jiayan Chen
- Department of Radiation Oncology, Peking University First Hospital, Beijing 100034, China
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Li S, Zhang H, Zhu M, Kuang Z, Li X, Xu F, Miao S, Zhang Z, Lou X, Li H, Xia F. Electrochemical Biosensors for Whole Blood Analysis: Recent Progress, Challenges, and Future Perspectives. Chem Rev 2023. [PMID: 37262362 DOI: 10.1021/acs.chemrev.1c00759] [Citation(s) in RCA: 76] [Impact Index Per Article: 38.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
Whole blood, as one of the most significant biological fluids, provides critical information for health management and disease monitoring. Over the past 10 years, advances in nanotechnology, microfluidics, and biomarker research have spurred the development of powerful miniaturized diagnostic systems for whole blood testing toward the goal of disease monitoring and treatment. Among the techniques employed for whole-blood diagnostics, electrochemical biosensors, as known to be rapid, sensitive, capable of miniaturization, reagentless and washing free, become a class of emerging technology to achieve the target detection specifically and directly in complex media, e.g., whole blood or even in the living body. Here we are aiming to provide a comprehensive review to summarize advances over the past decade in the development of electrochemical sensors for whole blood analysis. Further, we address the remaining challenges and opportunities to integrate electrochemical sensing platforms.
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Affiliation(s)
- Shaoguang Li
- State Key Laboratory of Biogeology and Environmental Geology, Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan 430074, China
| | - Hongyuan Zhang
- State Key Laboratory of Biogeology and Environmental Geology, Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan 430074, China
| | - Man Zhu
- State Key Laboratory of Biogeology and Environmental Geology, Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan 430074, China
| | - Zhujun Kuang
- State Key Laboratory of Biogeology and Environmental Geology, Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan 430074, China
| | - Xun Li
- State Key Laboratory of Biogeology and Environmental Geology, Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan 430074, China
| | - Fan Xu
- State Key Laboratory of Biogeology and Environmental Geology, Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan 430074, China
| | - Siyuan Miao
- State Key Laboratory of Biogeology and Environmental Geology, Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan 430074, China
| | - Zishuo Zhang
- State Key Laboratory of Biogeology and Environmental Geology, Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan 430074, China
| | - Xiaoding Lou
- State Key Laboratory of Biogeology and Environmental Geology, Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan 430074, China
| | - Hui Li
- State Key Laboratory of Biogeology and Environmental Geology, Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan 430074, China
| | - Fan Xia
- State Key Laboratory of Biogeology and Environmental Geology, Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan 430074, China
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Martino S, Tammaro C, Misso G, Falco M, Scrima M, Bocchetti M, Rea I, De Stefano L, Caraglia M. microRNA Detection via Nanostructured Biochips for Early Cancer Diagnostics. Int J Mol Sci 2023; 24:7762. [PMID: 37175469 PMCID: PMC10178165 DOI: 10.3390/ijms24097762] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 04/15/2023] [Accepted: 04/21/2023] [Indexed: 05/15/2023] Open
Abstract
MicroRNA (miRNA) are constituted of approximately 22 nucleotides and play an important role in the regulation of many physiological functions and diseases. In the last 10 years, an increasing interest has been recorded in studying the expression profile of miRNAs in cancer. Real time-quantitative polymerase chain reaction (RT-qPCR), microarrays, and small RNA sequencing represent the gold standard techniques used in the last 30 years as detection methods. The advent of nanotechnology has allowed the fabrication of nanostructured biosensors which are widely exploited in the diagnostic field. Nanostructured biosensors offer many advantages: (i) their small size allows the construction of portable, wearable, and low-cost products; (ii) the large surface-volume ratio enables the loading of a great number of biorecognition elements (e.g., probes, receptors); and (iii) direct contact of the recognition element with the analyte increases the sensitivity and specificity inducing low limits of detection (LOD). In this review, the role of nanostructured biosensors in miRNA detection is explored, focusing on electrochemical and optical sensing. In particular, four types of nanomaterials (metallic nanoparticles, graphene oxide, quantum dots, and nanostructured polymers) are reported for both detection strategies with the aim to show their distinct properties and applications.
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Affiliation(s)
- Sara Martino
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (S.M.); (C.T.); (M.F.); (M.B.); (M.C.)
- Unit of Naples, National Research Council, Institute of Applied Sciences and Intelligent Systems, 80138 Naples, Italy;
| | - Chiara Tammaro
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (S.M.); (C.T.); (M.F.); (M.B.); (M.C.)
| | - Gabriella Misso
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (S.M.); (C.T.); (M.F.); (M.B.); (M.C.)
| | - Michela Falco
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (S.M.); (C.T.); (M.F.); (M.B.); (M.C.)
- Laboratory of Molecular and Precision Oncology, Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy;
| | - Marianna Scrima
- Laboratory of Molecular and Precision Oncology, Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy;
| | - Marco Bocchetti
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (S.M.); (C.T.); (M.F.); (M.B.); (M.C.)
- Laboratory of Molecular and Precision Oncology, Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy;
| | - Ilaria Rea
- Unit of Naples, National Research Council, Institute of Applied Sciences and Intelligent Systems, 80138 Naples, Italy;
| | - Luca De Stefano
- Unit of Naples, National Research Council, Institute of Applied Sciences and Intelligent Systems, 80138 Naples, Italy;
| | - Michele Caraglia
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (S.M.); (C.T.); (M.F.); (M.B.); (M.C.)
- Laboratory of Molecular and Precision Oncology, Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy;
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Lipid metabolism-related miRNAs with potential diagnostic roles in prostate cancer. Lipids Health Dis 2023; 22:39. [PMID: 36915125 PMCID: PMC10012590 DOI: 10.1186/s12944-023-01804-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Accepted: 03/07/2023] [Indexed: 03/16/2023] Open
Abstract
BACKGROUND Prostate cancer (PCa), the second most prevalent solid tumor among men worldwide, has caused greatly increasing mortality in PCa patients. The effects of lipid metabolism on tumor growth have been explored, but the mechanistic details of the association of lipid metabolism disorders with PCa remain largely elusive. METHODS The RNA sequencing data of the GSE45604 and The Cancer Genome Atlas-Prostate Adenocarcinoma (TCGA-PRAD) datasets were extracted from the Gene Expression Omnibus (GEO) and UCSC Xena databases, respectively. The Molecular Signatures Database (MSigDB) was utilized to identify lipid metabolism-related genes. The limma R package was used to identify differentially expressed lipid metabolism-related genes (DE-LMRGs) and differentially expressed microRNAs (DEMs). Moreover, least absolute shrinkage and selection operator (LASSO), extreme gradient boosting (XGBoost), and support vector machine-recursive feature elimination (SVM-RFE) were applied to select signature miRNAs and construct a lipid metabolism-related diagnostic model. The expression levels of selected differentially expressed lipid metabolism-related miRNAs (DE-LMRMs) in PCa and benign prostate hyperplasia (BPH) specimens were verified using quantitative real-time polymerase chain reaction (qRT‒PCR). Furthermore, a transcription factor (TF)-miRNA‒mRNA network was constructed. Eventually, Kaplan‒Meier (KM) curves were plotted to illustrate the associations between signature miRNA-related mRNAs and TFs and overall survival (OS) along with biochemical recurrence-free survival (BCR). RESULTS Forty-seven LMRMs were screened based on the correlation analysis of 29 DE-LMRGs and 56 DEMs, in which 27 LMRMs were stably expressed in the GSE45604 dataset. Subsequently, receiver operating characteristic (ROC) curves and machine learning methods were employed to develop a lipid metabolism-related diagnostic signature, which may be of diagnostic value for PCa patients. qRT‒PCR results showed that all seven key DE-LMRMs were differentially expressed between PCa and BPH tissues. Eventually, a TF-miRNA‒mRNA network was constructed. CONCLUSIONS These results suggested that 7 key diagnostic miRNAs were closely related to PCa pathological processes and provided new targets for the diagnosis and treatment of PCa. Moreover, CLIC6 and SCNN1A linked to miR-200c-3p had good prognostic potential and provided valuable insights into the pathogenesis of PCa.
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Jafari A, Karimabadi K, Rahimi A, Rostaminasab G, Khazaei M, Rezakhani L, Ahmadi jouybari T. The Emerging Role of Exosomal miRNAs as Biomarkers for Early Cancer Detection: A Comprehensive Literature Review. Technol Cancer Res Treat 2023; 22:15330338231205999. [PMID: 37817634 PMCID: PMC10566290 DOI: 10.1177/15330338231205999] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 09/10/2023] [Accepted: 09/13/2023] [Indexed: 10/12/2023] Open
Abstract
A significant number of cancer-related deaths are recorded globally each year, despite attempts to cure this illness. Medical science is working to develop new medication therapies as well as to find ways to identify this illness as early as possible, even using noninvasive techniques. Early detection of cancer can greatly aid its treatment. Studies into cancer diagnosis and therapy have recently shifted their focus to exosome (EXO) biomarkers, which comprise numerous RNA and proteins. EXOs are minuscule goblet vesicles that have a width of 30 to 140 nm and are released by a variety of cells, including immune, stem, and tumor cells, as well as bodily fluids. According to a growing body of research, EXOs, and cancer appear to be related. EXOs from tumors play a role in the genetic information transfer between tumor and basal cells, which controls angiogenesis and fosters tumor development and spread. To identify malignant activities early on, microRNAs (miRNAs) from cancers can be extracted from circulatory system EXOs. Specific markers can be used to identify cancer-derived EXOs containing miRNAs, which may be more reliable and precise for early detection. Conventional solid biopsy has become increasingly limited as precision and personalized medicine has advanced, while liquid biopsy offers a viable platform for noninvasive diagnosis and prognosis. Therefore, the use of body fluids such as serum, plasma, urine, and salivary secretions can help find cancer biomarkers using technologies related to EXOs.
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Affiliation(s)
- Ali Jafari
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Keyvan Karimabadi
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Aso Rahimi
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Gelavizh Rostaminasab
- Clinical Research Development Center, Imam Khomeini and Mohammad Kermanshahi and Farabi Hospitals, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mozafar Khazaei
- Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Department of Tissue Engineering, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Leila Rezakhani
- Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Department of Tissue Engineering, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Touraj Ahmadi jouybari
- Clinical Research Development Center, Imam Khomeini and Mohammad Kermanshahi and Farabi Hospitals, Kermanshah University of Medical Sciences, Kermanshah, Iran
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18
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The Potential of MicroRNAs as Non-Invasive Prostate Cancer Biomarkers: A Systematic Literature Review Based on a Machine Learning Approach. Cancers (Basel) 2022; 14:cancers14215418. [PMID: 36358836 PMCID: PMC9657574 DOI: 10.3390/cancers14215418] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Revised: 10/28/2022] [Accepted: 10/30/2022] [Indexed: 11/06/2022] Open
Abstract
Simple Summary Prostate cancer (PCa) is the most common cancer in men worldwide. Screening and diagnosis are based on prostate-specific antigen (PSA) blood testing and digital rectal examination. Nevertheless, these methods are not specific and have a high risk of mistaken results. This has led to overtreatment and unnecessary radical therapy; thus, better prognostic tools are urgently needed. In this view, microRNAs (miRs) appear as potential non-invasive biomarkers for PCa diagnosis, prognosis, and therapy. As the scientific literature available in this field is huge and very often controversial, we identified and discussed three topics that characterize the investigated research area by combining the big data from the literature together with a novel machine learning approach. By analyzing the papers clustered into these topics we have offered a deeper understanding of the current research, which helps to contribute to the advancement of this research field. Abstract Background: Prostate cancer (PCa) is the second leading cause of cancer-related deaths in men. Although the prostate-specific antigen (PSA) test is used in clinical practice for screening and/or early detection of PCa, it is not specific, thus resulting in high false-positive rates. MicroRNAs (miRs) provide an opportunity as biomarkers for diagnosis, prognosis, and recurrence of PCa. Because the size of the literature on it is increasing and often controversial, this study aims to consolidate the state-of-art of relevant published research. Methods: A Systematic Literature Review (SLR) approach was applied to analyze a set of 213 scientific publications through a text mining method that makes use of the Latent Dirichlet Allocation (LDA) algorithm. Results and Conclusions: The result of this activity, performed through the MySLR digital platform, allowed us to identify a set of three relevant topics characterizing the investigated research area. We analyzed and discussed all the papers clustered into them. We highlighted that several miRs are associated with PCa progression, and that their detection in patients’ urine seems to be the more reliable and promising non-invasive tool for PCa diagnosis. Finally, we proposed some future research directions to help future scientists advance the field further.
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Su F, Gao Z, Liu Y, Zhou G, Gao W, Deng C, Liu Y, Zhang Y, Ma X, Wang Y, Guan L, Zhang Y, Liu B. Prioritizing key synergistic circulating microRNAs for the early diagnosis of biliary tract cancer. Front Oncol 2022; 12:968412. [PMID: 36276146 PMCID: PMC9582275 DOI: 10.3389/fonc.2022.968412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 09/20/2022] [Indexed: 11/13/2022] Open
Abstract
Biliary tract cancer (BTC) is a highly aggressive malignant tumor. Serum microRNAs (ser-miRNAs) serve as noninvasive biomarkers to identify high risk individuals, thereby facilitating the design of precision therapies. The study is to prioritize key synergistic ser-miRNAs for the diagnosis of early BTC. Sampling technology, significant analysis of microarrays, Pearson Correlation Coefficients, t-test, decision tree, and entropy weight were integrated to develop a global optimization algorithm of decision forest. The source code is available at https://github.com/SuFei-lab/GOADF.git. Four key synergistic ser-miRNAs were prioritized and the synergistic classification performance was better than the single miRNA’ s. In the internal feature evaluation dataset, the area under the receiver operating characteristic curve (AUC) for each single miRNA was 0.8413 (hsa-let-7c-5p), 0.7143 (hsa-miR-16-5p), 0.8571 (hsa-miR-17-5p), and 0.9365 (hsa-miR-26a-5p), respectively, whereas the synergistic AUC value increased to 1.0000. In the internal test dataset, the single AUC was 0.6500, 0.5125, 0.6750, and 0.7500, whereas the synergistic AUC increased to 0.8375. In the independent test dataset, the single AUC was 0.7280, 0.8313, 0.8957, and 0.8303, and the synergistic AUC was 0.9110 for discriminating between BTC patients and healthy controls. The AUC for discriminating BTC from pancreatic cancer was 0.9000. Hsa-miR-26a-5p was a predictor of prognosis, patients with high expression had shorter survival than those with low expression. In conclusion, hsa-let-7c-5p, hsa-miR-16-5p, hsa-miR-17-5p, and hsa-miR-26a-5p may act as key synergistic biomarkers and provide important molecular mechanisms that contribute to pathogenesis of BTC.
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Affiliation(s)
- Fei Su
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China
| | - Ziyu Gao
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China
- Department of Anatomy, Harbin Medical University, Harbin, China
| | - Yueyang Liu
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China
| | - Guiqin Zhou
- Department of Immunology, Harbin Medical University, Harbin, China
| | - Wei Gao
- Laboratory of Medical Genetics, Harbin Medical University, Harbin, China
| | - Chao Deng
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China
- Department of Anatomy, Harbin Medical University, Harbin, China
| | - Yuyu Liu
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China
- Department of Anatomy, Harbin Medical University, Harbin, China
| | - Yihao Zhang
- Department of Anatomy, Harbin Medical University, Harbin, China
| | - Xiaoyan Ma
- Department of Anatomy, Harbin Medical University, Harbin, China
| | - Yongxia Wang
- Department of Anatomy, Harbin Medical University, Harbin, China
| | - Lili Guan
- Department of Information Management, Shanghai Lixin University of Accounting and Finance, Shanghai, China
- *Correspondence: Baoquan Liu, ; Yafang Zhang, ; Lili Guan,
| | - Yafang Zhang
- Department of Anatomy, Harbin Medical University, Harbin, China
- *Correspondence: Baoquan Liu, ; Yafang Zhang, ; Lili Guan,
| | - Baoquan Liu
- Department of Anatomy, Harbin Medical University, Harbin, China
- Department of Modern Medicine and Pharmacy, University of Tibetan Medicine, Lhasa, China
- *Correspondence: Baoquan Liu, ; Yafang Zhang, ; Lili Guan,
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de Nóbrega M, Dos Reis MB, Pereira ÉR, de Souza MF, de Syllos Cólus IM. The potential of cell-free and exosomal microRNAs as biomarkers in liquid biopsy in patients with prostate cancer. J Cancer Res Clin Oncol 2022; 148:2893-2910. [PMID: 35922694 DOI: 10.1007/s00432-022-04213-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Accepted: 07/14/2022] [Indexed: 12/19/2022]
Abstract
PURPOSE Prostate cancer (PCa) is the 4th most diagnosed cancer and the 8th leading cause of cancer-related death worldwide. Currently, clinical risk stratification models including factors like PSA levels, Gleason score, and digital rectal examination are used for this purpose. There is a need for novel biomarkers that can distinguish between indolent and aggressive pathology and reduce the risk of overdiagnosis/overtreatment. Liquid biopsy has a non-invasive character, can lead to less morbidity and provide new biomarkers, such as miRNAs, that regulate diverse important cellular processes. Here, we report an extended revision about the role of cell-free and exosomal miRNAs (exomiRNAs) as biomarkers for screening, diagnosis, prognosis, or treatment of PCa. METHODS A comprehensive review of the published literature was conducted focusing on the usefulness, advantages, and clinical applications of cell-free and exomiRNAs in serum and plasma. Using PubMed database 53 articles published between 2012 and 2021 were selected and discussed from the perspective of their use as diagnostic, prognostic and therapeutic biomarkers for PCa. RESULTS We identify 119 miRNAs associated with PCa development and the cell-free and exosomal miR-21, miR-141, miR-200c, and miR-375 were consistently associated with progression in multiple cohorts/studies. However, standardized experimental procedures, and well-defined and clinically relevant cohort studies are urgently needed to confirm the biomarker potential of cell-free and exomiRNAs in serum or plasma. CONCLUSION Cell-free and exomiRNAs in serum or plasma are promising tools for be used as non-invasive biomarkers for diagnostic, prognosis, therapy improvement and clinical outcome prediction in PCa patients.
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Affiliation(s)
- Monyse de Nóbrega
- Department of General Biology, Laboratory of Mutagenesis and Oncogenetics, Center of Biologic Sciences, State University of Londrina, Rodovia Celso Garcia Cid, PR-445, Km 380-University Campus, Londrina, PR, CEP 86057-970, Brazil
| | - Mariana Bisarro Dos Reis
- Barretos Cancer Hospital (Molecular Oncology Research Center), Barretos, SP, CEP 14784-400, Brazil
| | - Érica Romão Pereira
- Department of General Biology, Laboratory of Mutagenesis and Oncogenetics, Center of Biologic Sciences, State University of Londrina, Rodovia Celso Garcia Cid, PR-445, Km 380-University Campus, Londrina, PR, CEP 86057-970, Brazil
| | - Marilesia Ferreira de Souza
- Department of General Biology, Laboratory of Mutagenesis and Oncogenetics, Center of Biologic Sciences, State University of Londrina, Rodovia Celso Garcia Cid, PR-445, Km 380-University Campus, Londrina, PR, CEP 86057-970, Brazil
| | - Ilce Mara de Syllos Cólus
- Department of General Biology, Laboratory of Mutagenesis and Oncogenetics, Center of Biologic Sciences, State University of Londrina, Rodovia Celso Garcia Cid, PR-445, Km 380-University Campus, Londrina, PR, CEP 86057-970, Brazil.
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21
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Coley AB, DeMeis JD, Chaudhary NY, Borchert GM. Small Nucleolar Derived RNAs as Regulators of Human Cancer. Biomedicines 2022; 10:1819. [PMID: 36009366 PMCID: PMC9404758 DOI: 10.3390/biomedicines10081819] [Citation(s) in RCA: 10] [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: 05/30/2022] [Revised: 07/19/2022] [Accepted: 07/21/2022] [Indexed: 11/25/2022] Open
Abstract
In the past decade, RNA fragments derived from full-length small nucleolar RNAs (snoRNAs) have been shown to be specifically excised and functional. These sno-derived RNAs (sdRNAs) have been implicated as gene regulators in a multitude of cancers, controlling a variety of genes post-transcriptionally via association with the RNA-induced silencing complex (RISC). In this review, we have summarized the literature connecting sdRNAs to cancer gene regulation. SdRNAs possess miRNA-like functions and are able to fill the role of tumor-suppressing or tumor-promoting RNAs in a tissue context-dependent manner. Indeed, there are many miRNAs that are actually derived from snoRNA transcripts, meaning that they are truly sdRNAs and as such are included in this review. As sdRNAs are frequently discarded from ncRNA analyses, we emphasize that sdRNAs are functionally relevant gene regulators and likely represent an overlooked subclass of miRNAs. Based on the evidence provided by the papers reviewed here, we propose that sdRNAs deserve more extensive study to better understand their underlying biology and to identify previously overlooked biomarkers and therapeutic targets for a multitude of human cancers.
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Affiliation(s)
- Alexander Bishop Coley
- Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA; (A.B.C.); (J.D.D.); (N.Y.C.)
| | - Jeffrey David DeMeis
- Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA; (A.B.C.); (J.D.D.); (N.Y.C.)
| | - Neil Yash Chaudhary
- Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA; (A.B.C.); (J.D.D.); (N.Y.C.)
| | - Glen Mark Borchert
- Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA; (A.B.C.); (J.D.D.); (N.Y.C.)
- School of Computing, University of South Alabama, Mobile, AL 36688, USA
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22
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Crocetto F, Russo G, Di Zazzo E, Pisapia P, Mirto BF, Palmieri A, Pepe F, Bellevicine C, Russo A, La Civita E, Terracciano D, Malapelle U, Troncone G, Barone B. Liquid Biopsy in Prostate Cancer Management—Current Challenges and Future Perspectives. Cancers (Basel) 2022; 14:cancers14133272. [PMID: 35805043 PMCID: PMC9265840 DOI: 10.3390/cancers14133272] [Citation(s) in RCA: 65] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 06/28/2022] [Accepted: 07/01/2022] [Indexed: 02/04/2023] Open
Abstract
Simple Summary Prostate cancer (PCa) is a widespread malignancy, representing the second leading cause of cancer-related death in men. In the last years, liquid biopsy has emerged as an attractive and promising strategy complementary to invasive tissue biopsy to guide PCa diagnosis, follow-up and treatment response. Liquid biopsy is employed to assess several body fluids biomarkers, including circulating tumor cells (CTCs), extracellular vesicles (EVs), circulating tumor DNA (ctDNA) and RNA (ctRNA). This review dissects recent advancements and future perspectives of liquid biopsy, highlighting its strength and weaknesses in PCa management. Abstract Although appreciable attempts in screening and diagnostic approaches have been achieved, prostate cancer (PCa) remains a widespread malignancy, representing the second leading cause of cancer-related death in men. Drugs currently used in PCa therapy initially show a potent anti-tumor effect, but frequently induce resistance and PCa progresses toward metastatic castration-resistant forms (mCRPC), virtually incurable. Liquid biopsy has emerged as an attractive and promising strategy complementary to invasive tissue biopsy to guide PCa diagnosis and treatment. Liquid biopsy shows the ability to represent the tumor microenvironment, allow comprehensive information and follow-up the progression of the tumor, enabling the development of different treatment strategies as well as permitting the monitoring of therapy response. Liquid biopsy, indeed, is endowed with a significant potential to modify PCa management. Several blood biomarkers could be analyzed for diagnostic, prognostic and predictive purposes, including circulating tumor cells (CTCs), extracellular vesicles (EVs), circulating tumor DNA (ctDNA) and RNA (ctRNA). In addition, several other body fluids may be adopted (i.e., urine, sperm, etc.) beyond blood. This review dissects recent advancements and future perspectives of liquid biopsies, highlighting their strength and weaknesses in PCa management.
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Affiliation(s)
- Felice Crocetto
- Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples “Federico II”, 80131 Naples, Italy; (F.C.); (B.F.M.); (A.P.); (B.B.)
| | - Gianluca Russo
- Department of Public Health, University of Naples Federico II, 80131 Naples, Italy; (G.R.); (P.P.); (F.P.); (C.B.); (U.M.); (G.T.)
| | - Erika Di Zazzo
- Department of Medicine and Health Sciences “V. Tiberio”, University of Molise, 86100 Campobasso, Italy
- Correspondence:
| | - Pasquale Pisapia
- Department of Public Health, University of Naples Federico II, 80131 Naples, Italy; (G.R.); (P.P.); (F.P.); (C.B.); (U.M.); (G.T.)
| | - Benito Fabio Mirto
- Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples “Federico II”, 80131 Naples, Italy; (F.C.); (B.F.M.); (A.P.); (B.B.)
| | - Alessandro Palmieri
- Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples “Federico II”, 80131 Naples, Italy; (F.C.); (B.F.M.); (A.P.); (B.B.)
| | - Francesco Pepe
- Department of Public Health, University of Naples Federico II, 80131 Naples, Italy; (G.R.); (P.P.); (F.P.); (C.B.); (U.M.); (G.T.)
| | - Claudio Bellevicine
- Department of Public Health, University of Naples Federico II, 80131 Naples, Italy; (G.R.); (P.P.); (F.P.); (C.B.); (U.M.); (G.T.)
| | | | - Evelina La Civita
- Department of Translational Medical Sciences, University of Naples “Federico II”, 80131 Naples, Italy; (E.L.C.); (D.T.)
| | - Daniela Terracciano
- Department of Translational Medical Sciences, University of Naples “Federico II”, 80131 Naples, Italy; (E.L.C.); (D.T.)
| | - Umberto Malapelle
- Department of Public Health, University of Naples Federico II, 80131 Naples, Italy; (G.R.); (P.P.); (F.P.); (C.B.); (U.M.); (G.T.)
| | - Giancarlo Troncone
- Department of Public Health, University of Naples Federico II, 80131 Naples, Italy; (G.R.); (P.P.); (F.P.); (C.B.); (U.M.); (G.T.)
| | - Biagio Barone
- Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples “Federico II”, 80131 Naples, Italy; (F.C.); (B.F.M.); (A.P.); (B.B.)
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23
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Schwartz‐Duval AS, Sokolov KV. Prospecting Cellular Gold Nanoparticle Biomineralization as a Viable Alternative to Prefabricated Gold Nanoparticles. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2022; 9:e2105957. [PMID: 35508715 PMCID: PMC9284136 DOI: 10.1002/advs.202105957] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 03/17/2022] [Indexed: 06/14/2023]
Abstract
Gold nanoparticles (GNPs) have shown considerable potential in a vast number of biomedical applications. However, currently there are no clinically approved injectable GNP formulations. Conversely, gold salts have been used in the clinic for nearly a century. Further, there is evidence of GNP formation in patients treated with gold salts (i.e., chrysiasis). Recent reports evaluating this phenomenon in human cells and in murine models indicate that the use of gold ions for in situ formation of theranostic GNPs could greatly improve the delivery within dense biological tissues, increase efficiency of intracellular gold uptake, and specificity of GNP formation within cancer cells. These attributes in combination with safe clinical application of gold salts make this process a viable strategy for clinical translation. Here, the first summary of the current knowledge related to GNP biomineralization in mammalian cells is provided along with critical assessment of potential biomedical applications of this newly emergent field.
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Affiliation(s)
- Aaron S. Schwartz‐Duval
- Department of Imaging PhysicsThe University of Texas MD Anderson Cancer Center1515 Holcombe BoulevardHoustonTX77030USA
| | - Konstantin V. Sokolov
- Department of Imaging PhysicsThe University of Texas MD Anderson Cancer Center1515 Holcombe BoulevardHoustonTX77030USA
- The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences6767 Bertner AveHoustonTX77030USA
- Department of BioengineeringRice University6100 Main St.HoustonTX77030USA
- Department of Biomedical EngineeringThe University of Texas at Austin107 W Dean Keeton St.AustinTX78712USA
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24
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Liu H, Huang Y, Huang M, Huang Z, Wang Q, Qing L, Li L, Xu S, Jia B. Current Status, Opportunities, and Challenges of Exosomes in Oral Cancer Diagnosis and Treatment. Int J Nanomedicine 2022; 17:2679-2705. [PMID: 35733418 PMCID: PMC9208818 DOI: 10.2147/ijn.s365594] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 06/01/2022] [Indexed: 12/13/2022] Open
Abstract
Oral cancer is one of the most common cancers in the world, with more than 300,000 cases diagnosed each year, of which oral squamous cell carcinoma accounts for more than 90%, with a 5-year survival rate of only 40–60%, and poor prognosis. Exploring new strategies for the early diagnosis and treatment of oral cancer is key to improving the survival rate. Exosomes are nanoscale lipid bilayer membrane vesicles that are secreted by almost all cell types. During the development of oral cancer, exosomes can transport their contents (DNA, RNA, proteins, etc) to target cells and promote or inhibit the proliferation, invasion, and metastasis of oral cancer cells by influencing the host immune response, drug-resistant metastasis, and tumour angiogenesis. Therefore, exosomes have great potential and advantages as biomarkers for oral cancer diagnosis, and as drug delivery vehicles or targets for oral cancer therapy. In this review, we first describe the biogenesis, biological functions, and isolation methods of exosomes, followed by their relationship with oral cancer. Here, we focused on the potential of exosomes as oral cancer biomarkers, drug carriers, and therapeutic targets. Finally, we provide an insightful discussion of the opportunities and challenges of exosome application in oral cancer diagnosis and treatment, intending to offer new ideas for the clinical management of oral cancer.
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Affiliation(s)
- Hongyu Liu
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, People's Republic of China
| | - Yisheng Huang
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, People's Republic of China
| | - Mingshu Huang
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, People's Republic of China
| | - Zhijie Huang
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, People's Republic of China
| | - Qin Wang
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, People's Republic of China
| | - Ling Qing
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, People's Republic of China
| | - Li Li
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, People's Republic of China
| | - Shuaimei Xu
- Department of Endodontics, Stomatological Hospital, Southern Medical University, Guangzhou, People's Republic of China
| | - Bo Jia
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, People's Republic of China
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25
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Luo Y, Fan C, Song Y, Xu T, Zhang X. Ultra-trace enriching biosensing in nanoliter sample. Biosens Bioelectron 2022; 210:114297. [PMID: 35472656 DOI: 10.1016/j.bios.2022.114297] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 04/11/2022] [Accepted: 04/18/2022] [Indexed: 11/02/2022]
Abstract
Rapid detection and accurate analysis of trace samples is an important prerequisite for precision medicine. Here we integrated capillary with ultrasound to induce biomarkers enrichment in nanoliter samples, and developed a nanoliter sample enrichment analysis method for ultra-trace miRNA biosensing. The interaction between ultrasonic field and capillary provides a gradient ultrasound field, which is essential for the aggregation of functionalized microspheres along with the enrichment of specific biomarkers. The results indicated that the enrichment of the biomarkers effectively enhanced the fluorescence intensity, and the limit of detection reaches 7.8✕10-12 M in 100 nL. Such integrated device can realize ultrasonic enrichment and visual analysis of target samples, and provides a new idea for rapid and highly sensitive detection of ultra-trace biomarkers in clinical diagnosis.
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Affiliation(s)
- Yong Luo
- Beijing Key Laboratory for Bioengineering and Sensing Technology, University of Science and Technology Beijing, Beijing, 100083, PR China
| | - Chuan Fan
- Beijing Key Laboratory for Bioengineering and Sensing Technology, University of Science and Technology Beijing, Beijing, 100083, PR China
| | - Yongchao Song
- Beijing Key Laboratory for Bioengineering and Sensing Technology, University of Science and Technology Beijing, Beijing, 100083, PR China
| | - Tailin Xu
- Beijing Key Laboratory for Bioengineering and Sensing Technology, University of Science and Technology Beijing, Beijing, 100083, PR China; School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, Guangdong, 518060, PR China.
| | - Xueji Zhang
- School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, Guangdong, 518060, PR China
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26
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Coley AB, Stahly AN, Kasukurthi MV, Barchie AA, Hutcheson SB, Houserova D, Huang Y, Watters BC, King VM, Dean MA, Roberts JT, DeMeis JD, Amin KV, McInnis CH, Godang NL, Wright RM, Haider DF, Piracha NB, Brown CL, Ijaz ZM, Li S, Xi Y, McDonald OG, Huang J, Borchert GM. MicroRNA-like snoRNA-Derived RNAs (sdRNAs) Promote Castration-Resistant Prostate Cancer. Cells 2022; 11:1302. [PMID: 35455981 PMCID: PMC9032336 DOI: 10.3390/cells11081302] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 04/06/2022] [Accepted: 04/10/2022] [Indexed: 12/13/2022] Open
Abstract
We have identified 38 specifically excised, differentially expressed snoRNA fragments (sdRNAs) in TCGA prostate cancer (PCa) patient samples as compared to normal prostate controls. SnoRNA-derived fragments sdRNA-D19b and -A24 emerged among the most differentially expressed and were selected for further experimentation. We found that the overexpression of either sdRNA significantly increased PC3 (a well-established model of castration-resistant prostate cancer (CRPC)) cell proliferation, and that sdRNA-D19b overexpression also markedly increased the rate of PC3 cell migration. In addition, both sdRNAs provided drug-specific resistances with sdRNA-D19b levels correlating with paclitaxel resistance and sdRNA-24A conferring dasatinib resistance. In silico and in vitro analyses revealed that two established PCa tumor suppressor genes, CD44 and CDK12, represent targets for sdRNA-D19b and sdRNA-A24, respectively. This outlines a biologically coherent mechanism by which sdRNAs downregulate tumor suppressors in AR-PCa to enhance proliferative and metastatic capabilities and to encourage chemotherapeutic resistance. Aggressive proliferation, rampant metastasis, and recalcitrance to chemotherapy are core characteristics of CRPC that synergize to produce a pathology that ranks second in cancer-related deaths for men. This study defines sdRNA-D19b and -A24 as contributors to AR-PCa, potentially providing novel biomarkers and therapeutic targets of use in PCa clinical intervention.
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Affiliation(s)
- Alexander B. Coley
- Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA; (A.B.C.); (A.A.B.); (S.B.H.); (D.H.); (Y.H.); (B.C.W.); (M.A.D.); (J.T.R.); (J.D.D.); (K.V.A.); (C.H.M.); (N.L.G.); (R.M.W.); (D.F.H.); (N.B.P.); (C.L.B.); (Z.M.I.)
| | - Ashlyn N. Stahly
- Medical Scientist Training Program, University of Colorado School of Medicine, Aurora, CO 80045, USA;
| | - Mohan V. Kasukurthi
- School of Computing, University of South Alabama, Mobile, AL 36608, USA; (M.V.K.); (S.L.); (J.H.)
| | - Addison A. Barchie
- Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA; (A.B.C.); (A.A.B.); (S.B.H.); (D.H.); (Y.H.); (B.C.W.); (M.A.D.); (J.T.R.); (J.D.D.); (K.V.A.); (C.H.M.); (N.L.G.); (R.M.W.); (D.F.H.); (N.B.P.); (C.L.B.); (Z.M.I.)
- Department of Biology, University of South Alabama, Mobile, AL 36608, USA;
| | - Sam B. Hutcheson
- Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA; (A.B.C.); (A.A.B.); (S.B.H.); (D.H.); (Y.H.); (B.C.W.); (M.A.D.); (J.T.R.); (J.D.D.); (K.V.A.); (C.H.M.); (N.L.G.); (R.M.W.); (D.F.H.); (N.B.P.); (C.L.B.); (Z.M.I.)
| | - Dominika Houserova
- Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA; (A.B.C.); (A.A.B.); (S.B.H.); (D.H.); (Y.H.); (B.C.W.); (M.A.D.); (J.T.R.); (J.D.D.); (K.V.A.); (C.H.M.); (N.L.G.); (R.M.W.); (D.F.H.); (N.B.P.); (C.L.B.); (Z.M.I.)
| | - Yulong Huang
- Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA; (A.B.C.); (A.A.B.); (S.B.H.); (D.H.); (Y.H.); (B.C.W.); (M.A.D.); (J.T.R.); (J.D.D.); (K.V.A.); (C.H.M.); (N.L.G.); (R.M.W.); (D.F.H.); (N.B.P.); (C.L.B.); (Z.M.I.)
| | - Brianna C. Watters
- Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA; (A.B.C.); (A.A.B.); (S.B.H.); (D.H.); (Y.H.); (B.C.W.); (M.A.D.); (J.T.R.); (J.D.D.); (K.V.A.); (C.H.M.); (N.L.G.); (R.M.W.); (D.F.H.); (N.B.P.); (C.L.B.); (Z.M.I.)
| | - Valeria M. King
- Department of Biology, University of South Alabama, Mobile, AL 36608, USA;
- Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720, USA
| | - Meghan A. Dean
- Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA; (A.B.C.); (A.A.B.); (S.B.H.); (D.H.); (Y.H.); (B.C.W.); (M.A.D.); (J.T.R.); (J.D.D.); (K.V.A.); (C.H.M.); (N.L.G.); (R.M.W.); (D.F.H.); (N.B.P.); (C.L.B.); (Z.M.I.)
- Department of Biology, University of South Alabama, Mobile, AL 36608, USA;
| | - Justin T. Roberts
- Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA; (A.B.C.); (A.A.B.); (S.B.H.); (D.H.); (Y.H.); (B.C.W.); (M.A.D.); (J.T.R.); (J.D.D.); (K.V.A.); (C.H.M.); (N.L.G.); (R.M.W.); (D.F.H.); (N.B.P.); (C.L.B.); (Z.M.I.)
- Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA
| | - Jeffrey D. DeMeis
- Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA; (A.B.C.); (A.A.B.); (S.B.H.); (D.H.); (Y.H.); (B.C.W.); (M.A.D.); (J.T.R.); (J.D.D.); (K.V.A.); (C.H.M.); (N.L.G.); (R.M.W.); (D.F.H.); (N.B.P.); (C.L.B.); (Z.M.I.)
- Department of Biology, University of South Alabama, Mobile, AL 36608, USA;
| | - Krisha V. Amin
- Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA; (A.B.C.); (A.A.B.); (S.B.H.); (D.H.); (Y.H.); (B.C.W.); (M.A.D.); (J.T.R.); (J.D.D.); (K.V.A.); (C.H.M.); (N.L.G.); (R.M.W.); (D.F.H.); (N.B.P.); (C.L.B.); (Z.M.I.)
| | - Cameron H. McInnis
- Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA; (A.B.C.); (A.A.B.); (S.B.H.); (D.H.); (Y.H.); (B.C.W.); (M.A.D.); (J.T.R.); (J.D.D.); (K.V.A.); (C.H.M.); (N.L.G.); (R.M.W.); (D.F.H.); (N.B.P.); (C.L.B.); (Z.M.I.)
- Department of Biology, University of South Alabama, Mobile, AL 36608, USA;
| | - Noel L. Godang
- Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA; (A.B.C.); (A.A.B.); (S.B.H.); (D.H.); (Y.H.); (B.C.W.); (M.A.D.); (J.T.R.); (J.D.D.); (K.V.A.); (C.H.M.); (N.L.G.); (R.M.W.); (D.F.H.); (N.B.P.); (C.L.B.); (Z.M.I.)
- Department of Biology, University of South Alabama, Mobile, AL 36608, USA;
| | - Ryan M. Wright
- Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA; (A.B.C.); (A.A.B.); (S.B.H.); (D.H.); (Y.H.); (B.C.W.); (M.A.D.); (J.T.R.); (J.D.D.); (K.V.A.); (C.H.M.); (N.L.G.); (R.M.W.); (D.F.H.); (N.B.P.); (C.L.B.); (Z.M.I.)
- Department of Biology, University of South Alabama, Mobile, AL 36608, USA;
| | - David F. Haider
- Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA; (A.B.C.); (A.A.B.); (S.B.H.); (D.H.); (Y.H.); (B.C.W.); (M.A.D.); (J.T.R.); (J.D.D.); (K.V.A.); (C.H.M.); (N.L.G.); (R.M.W.); (D.F.H.); (N.B.P.); (C.L.B.); (Z.M.I.)
- Department of Biology, University of South Alabama, Mobile, AL 36608, USA;
| | - Neha B. Piracha
- Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA; (A.B.C.); (A.A.B.); (S.B.H.); (D.H.); (Y.H.); (B.C.W.); (M.A.D.); (J.T.R.); (J.D.D.); (K.V.A.); (C.H.M.); (N.L.G.); (R.M.W.); (D.F.H.); (N.B.P.); (C.L.B.); (Z.M.I.)
- Department of Biology, University of South Alabama, Mobile, AL 36608, USA;
| | - Cana L. Brown
- Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA; (A.B.C.); (A.A.B.); (S.B.H.); (D.H.); (Y.H.); (B.C.W.); (M.A.D.); (J.T.R.); (J.D.D.); (K.V.A.); (C.H.M.); (N.L.G.); (R.M.W.); (D.F.H.); (N.B.P.); (C.L.B.); (Z.M.I.)
| | - Zohaib M. Ijaz
- Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA; (A.B.C.); (A.A.B.); (S.B.H.); (D.H.); (Y.H.); (B.C.W.); (M.A.D.); (J.T.R.); (J.D.D.); (K.V.A.); (C.H.M.); (N.L.G.); (R.M.W.); (D.F.H.); (N.B.P.); (C.L.B.); (Z.M.I.)
| | - Shengyu Li
- School of Computing, University of South Alabama, Mobile, AL 36608, USA; (M.V.K.); (S.L.); (J.H.)
| | - Yaguang Xi
- Department of Genetics, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA;
- Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
| | - Oliver G. McDonald
- Department of Pathology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33146, USA;
| | - Jingshan Huang
- School of Computing, University of South Alabama, Mobile, AL 36608, USA; (M.V.K.); (S.L.); (J.H.)
| | - Glen M. Borchert
- Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA; (A.B.C.); (A.A.B.); (S.B.H.); (D.H.); (Y.H.); (B.C.W.); (M.A.D.); (J.T.R.); (J.D.D.); (K.V.A.); (C.H.M.); (N.L.G.); (R.M.W.); (D.F.H.); (N.B.P.); (C.L.B.); (Z.M.I.)
- School of Computing, University of South Alabama, Mobile, AL 36608, USA; (M.V.K.); (S.L.); (J.H.)
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Larson NB, McDonnell SK, Fogarty Z, Liu Y, French AJ, Tillmans LS, Cheville JC, Wang L, Schaid DJ, Thibodeau SN. A microRNA Transcriptome-wide Association Study of Prostate Cancer Risk. Front Genet 2022; 13:836841. [PMID: 35432445 PMCID: PMC9006872 DOI: 10.3389/fgene.2022.836841] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 02/22/2022] [Indexed: 11/13/2022] Open
Abstract
Large genome-wide association studies have identified hundreds of single-nucleotide polymorphisms associated with increased risk of prostate cancer (PrCa), and many of these risk loci is presumed to confer regulatory effects on gene expression. While eQTL studies of long RNAs has yielded many potential risk genes, the relationship between PrCa risk genetics and microRNA expression dysregulation is understudied. We performed an microRNA transcriptome-wide association study of PrCa risk using small RNA sequencing and genome-wide genotyping data from N = 441 normal prostate epithelium tissue samples along with N = 411 prostate adenocarcinoma tumor samples from the Cancer Genome Atlas (TCGA). Genetically regulated expression prediction models were trained for all expressed microRNAs using the FUSION TWAS software. TWAS for PrCa risk was performed with both sets of models using single-SNP summary statistics from the recent PRACTICAL consortium PrCa case-control OncoArray GWAS meta-analysis. A total of 613 and 571 distinct expressed microRNAs were identified in the normal and tumor tissue datasets, respectively (overlap: 480). Among these, 79 (13%) normal tissue microRNAs demonstrated significant cis-heritability (median cis-h2 = 0.15, range: 0.03–0.79) for model training. Similar results were obtained from TCGA tumor samples, with 48 (9%) microRNA expression models successfully trained (median cis-h2 = 0.14, range: 0.06–0.60). Using normal tissue models, we identified two significant TWAS microRNA associations with PrCa risk: over-expression of mir-941 family microRNAs (PTWAS = 2.9E-04) and reduced expression of miR-3617-5p (PTWAS = 1.0E-03). The TCGA tumor TWAS also identified a significant association with miR-941 overexpression (PTWAS = 9.7E-04). Subsequent finemapping of the TWAS results using a multi-tissue database indicated limited evidence of causal status for each microRNA with PrCa risk (posterior inclusion probabilities <0.05). Future work will examine downstream regulatory effects of microRNA dysregulation as well as microRNA-mediated risk mechanisms via competing endogenous RNA relationships.
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Affiliation(s)
- Nicholas B. Larson
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, United States
- *Correspondence: Nicholas B. Larson,
| | - Shannon K. McDonnell
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, United States
| | - Zachary Fogarty
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, United States
| | - Yuanhang Liu
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, United States
| | - Amy J. French
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States
| | - Lori S. Tillmans
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States
| | - John C. Cheville
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States
| | - Liang Wang
- Department of Tumor Biology, H. Lee Moffitt Cancer Center, Tampa, FL, United States
| | - Daniel J. Schaid
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, United States
| | - Stephen N. Thibodeau
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States
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28
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Samami E, Pourali G, Arabpour M, Fanipakdel A, Shahidsales S, Javadinia SA, Hassanian SM, Mohammadparast S, Avan A. The Potential Diagnostic and Prognostic Value of Circulating MicroRNAs in the Assessment of Patients With Prostate Cancer: Rational and Progress. Front Oncol 2022; 11:716831. [PMID: 35186706 PMCID: PMC8855122 DOI: 10.3389/fonc.2021.716831] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Accepted: 12/31/2021] [Indexed: 12/20/2022] Open
Abstract
Prostate cancer (P.C.) is one of the most frequent diagnosed cancers among men and the first leading cause of death with an annual incidence of 1.4 million worldwide. Prostate-specific antigen is being used for screening/diagnosis of prostate disease, although it is associated with several limitations. Thus, identification of novel biomarkers is warranted for diagnosis of patients at earlier stages. MicroRNAs (miRNAs) are recently being emerged as potential biomarkers. It has been shown that these small molecules can be circulated in body fluids and prognosticate the risk of developing P.C. Several miRNAs, including MiR-20a, MiR-21, miR-375, miR-378, and miR-141, have been proposed to be expressed in prostate cancer. This review summarizes the current knowledge about possible molecular mechanisms and potential application of tissue specific and circulating microRNAs as diagnosis, prognosis, and therapeutic targets in prostate cancer.
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Affiliation(s)
- Elham Samami
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran University of Medical Sciences, Tehran, Iran
| | - Ghazaleh Pourali
- Cancer Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahla Arabpour
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Azar Fanipakdel
- Cancer Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Seyed Alireza Javadinia
- Vasei Clinical Research Development Unit, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | - Seyed Mahdi Hassanian
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Saeid Mohammadparast
- Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Amir Avan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Basic Medical Sciences Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- *Correspondence: Amir Avan,
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29
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Hu Y, Lv S, Wan J, Zheng C, Shao D, Wang H, Tao Y, Li M, Luo Y. Recent advances in nanomaterials for prostate cancer detection and diagnosis. J Mater Chem B 2022; 10:4907-4934. [PMID: 35712990 DOI: 10.1039/d2tb00448h] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Despite the significant progress in the discovery of biomarkers and the exploitation of technologies for prostate cancer (PCa) detection and diagnosis, the initial screening of these PCa-related biomarkers using current...
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Affiliation(s)
- Yongwei Hu
- Laboratory of Biomaterials and Translational Medicine, Center for Nanomedicine, Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
| | - Shixian Lv
- School of Materials Science and Engineering, Peking University, Beijing 100871, China
| | - Jiaming Wan
- Laboratory of Biomaterials and Translational Medicine, Center for Nanomedicine, Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
| | - Chunxiong Zheng
- Laboratory of Biomaterials and Translational Medicine, Center for Nanomedicine, Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
| | - Dan Shao
- Institutes of Life Sciences, School of Medicine, South China University of Technology, Guangzhou 510006, China
| | - Haixia Wang
- Laboratory of Biomaterials and Translational Medicine, Center for Nanomedicine, Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
| | - Yu Tao
- Laboratory of Biomaterials and Translational Medicine, Center for Nanomedicine, Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
| | - Mingqiang Li
- Laboratory of Biomaterials and Translational Medicine, Center for Nanomedicine, Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
- Guangdong Provincial Key Laboratory of Liver Disease, Guangzhou 510630, China
| | - Yun Luo
- Laboratory of Biomaterials and Translational Medicine, Center for Nanomedicine, Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
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30
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Gupta S, Mazumder P. Exosomes as diagnostic tools. Adv Clin Chem 2022; 110:117-144. [DOI: 10.1016/bs.acc.2022.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Abstract
Exosomes are a new horizon in modern therapy, presenting exciting new opportunities for advanced drug delivery and targeted release. Exosomes are small extracellular vesicles with a size range of 30-100 nm, secreted by all cell types in the human body and carrying a unique collection of DNA fragments, RNA species, lipids, protein biomarkers, transcription factors and metabolites. miRNAs are one of the most common RNA species in exosomes, and they play a role in a variety of biological processes including exocytosis, hematopoiesis and angiogenesis, as well as cellular communication via exosomes. Exosomes can act as cargo to transport this information from donor cells to near and long-distance target cells, participating in the reprogramming of recipient cells.
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Affiliation(s)
- Nihat Dilsiz
- Molecular Biology & Genetics, Faculty of Engineering & Natural Sciences, Istanbul Medeniyet University, Istanbul, 34700, Turkey
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Slabáková E, Kahounová Z, Procházková J, Souček K. Regulation of Neuroendocrine-like Differentiation in Prostate Cancer by Non-Coding RNAs. Noncoding RNA 2021; 7:ncrna7040075. [PMID: 34940756 PMCID: PMC8704250 DOI: 10.3390/ncrna7040075] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 11/18/2021] [Accepted: 11/29/2021] [Indexed: 12/21/2022] Open
Abstract
Neuroendocrine prostate cancer (NEPC) represents a variant of prostate cancer that occurs in response to treatment resistance or, to a much lesser extent, de novo. Unravelling the molecular mechanisms behind transdifferentiation of cancer cells to neuroendocrine-like cancer cells is essential for development of new treatment opportunities. This review focuses on summarizing the role of small molecules, predominantly microRNAs, in this phenomenon. A published literature search was performed to identify microRNAs, which are reported and experimentally validated to modulate neuroendocrine markers and/or regulators and to affect the complex neuroendocrine phenotype. Next, available patients’ expression datasets were surveyed to identify deregulated microRNAs, and their effect on NEPC and prostate cancer progression is summarized. Finally, possibilities of miRNA detection and quantification in body fluids of prostate cancer patients and their possible use as liquid biopsy in prostate cancer monitoring are discussed. All the addressed clinical and experimental contexts point to an association of NEPC with upregulation of miR-375 and downregulation of miR-34a and miR-19b-3p. Together, this review provides an overview of different roles of non-coding RNAs in the emergence of neuroendocrine prostate cancer.
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Ning JZ, Chu CM, Du Y, Zuo L. MiR-25 regulates cell proliferation and metastasis in bladder urothelial carcinoma. J Cancer 2021; 12:6706-6714. [PMID: 34659560 PMCID: PMC8517995 DOI: 10.7150/jca.62743] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 09/06/2021] [Indexed: 11/23/2022] Open
Abstract
Background: Bladder urothelial carcinoma (BC) is a common malignant tumor with a high incidence. This study aims to explore the role of miR-25 in BC tumorigenesis. Material and Methods: The expression of miR-25 and PTEN were detected in clinical BC tissues. BC cell lines T24 and 5637 were used to transfect miR-25 mimics or inhibitors. Luciferase reporter gene detection confirmed the correlation between miR-25 and PTEN. CCK-8 method and flow cytometry were used to detect cell viability and apoptosis. Cell migration and invasion ability were examined by transwell assays. Western blotting detects the protein levels of PTEN, β-catenin, GSK-3β and p-GSK-3β. Results: MiR-25 and PTEN expression are found to be negatively correlated in BC tissues. Further research confirmed that PTEN is a direct target of miR-25. In addition, the overexpression of miR-25 down-regulates the expression of PTEN, induces cell survival and inhibits apoptosis, while the knockout of miR-25 leads to the opposite result. miR-25 also inhibits the phosphorylation of GSK-3β and β-catenin without changing the total level of GSK-3β. In vivo experiments confirmed that miR-25 plays an oncogene's role by regulating the PTEN and Wnt/β-catenin signaling pathways. Conclusion: Our research shows that miR-25 has a negative regulatory effect on the expression of PTEN in clinical specimens and in vitro. miR-25 can promote the proliferation of BC cells and induce cell invasion. Therefore, miR-25 may be used as a biomarker to predict the progression of BC.
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Affiliation(s)
- Jin-Zhuo Ning
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, P.R.China
| | - Chuan-Min Chu
- Department of Urology, The Third Affiliated Hospital of Naval Medical University, Shanghai, P.R.China
| | - Yang Du
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, P.R.China
| | - Li Zuo
- Department of Urology, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu Province, P.R.China
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Lin BB, Lei HQ, Xiong HY, Fu X, Shi F, Yang XW, Yang YF, Liao GL, Feng YP, Jiang DG, Pang J. MicroRNA-regulated transcriptome analysis identifies four major subtypes with prognostic and therapeutic implications in prostate cancer. Comput Struct Biotechnol J 2021; 19:4941-4953. [PMID: 34527198 PMCID: PMC8433071 DOI: 10.1016/j.csbj.2021.08.046] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 08/28/2021] [Accepted: 08/29/2021] [Indexed: 12/12/2022] Open
Abstract
MicroRNA (miRNA) deregulation plays a critical role in the heterogeneous development of prostate cancer (PCa) by tuning mRNA levels. Herein, we aimed to characterize the molecular features of PCa by clustering the miRNA-regulated transcriptome with non-negative matrix factorization. Using 478 PCa samples from The Cancer Genome Atlas, four molecular subtypes (S-I, S-II, S-III, and S-IV) were identified and validated in two merged microarray and RNAseq datasets with 656 and 252 samples, respectively. Interestingly, the four subtypes showed distinct clinical and biological features after comprehensive analyses of clinical features, multiomic profiles, immune infiltration, and drug sensitivity. S-I is basal/stem/mesenchymal-like and immune-excluded with marked transforming growth factor β, epithelial-mesenchymal transition and hypoxia signals, increased sensitivity to olaparib, and intermediate prognosis. S-II is luminal/metabolism-active and responsive to androgen deprivation therapy with frequent TMPRSS2-ERG fusion and a good prognosis. S-III is characterized by moderate proliferative and metabolic activity, sensitivity to taxane-based chemotherapy, and intermediate prognosis. S-IV is highly proliferative with moderate EMT and stemness, frequent deletions of TP53, PTEN and RB, and the poorest prognosis; it is also immune-inflamed and sensitive to anti-PD-L1 therapy. Overall, based on miRNA-regulated gene profiles, this study identified four distinct PCa subtypes that could improve risk stratification at diagnosis and provide therapeutic guidance.
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Key Words
- ADT, androgen deprivation therapy
- AR, androgen receptor
- AUC, Area under the dose-response curve
- BCR, biochemical recurrence
- CAFs, cancer-associated fibroblasts
- CCLs, cancer cell lines
- CTLA-4, cytotoxic T-lymphocyte associated protein-4
- DEmiRs, differentially expressed miRNAs
- DFS, disease-free survival
- EMT, epithelial-mesenchymal transition
- FDR, false discovery rate
- GEO, Gene Expression Omnibus
- GEP, gene expression profile
- GO, Gene Ontology
- GSEA, Gene Set Enrichment Analysis
- Heterogeneity
- ICB, immune checkpoint blockade
- IFN, interferon
- KEGG, Kyoto Encyclopedia of Genes and Genomes
- MDSCs, myeloid-derived suppressor cells
- MIRcor, miRNA-correlated
- Molecular subtypes
- NEPC, neuroendocrine prostate cancer
- NMF, non-negative matrix factorization
- NTP, Nearest template prediction
- OS, overall survival
- PCa, prostate cancer
- PD-1, programmed cell death protein-1
- PD-L1, programmed death-ligand 1
- Prostate cancer
- SCNAs, somatic copy number alterations
- SubMap, Subclass mapping
- TCGA, The Cancer Genome Atlas
- TGFβ, transforming growth factor β
- TMB, tumor mutation burden
- TNAs, tumor neoantigens
- Tregs, regulatory T cells
- k-NN, K-nearest neighbor
- mCRPC, metastatic castration-resistant prostate cancer
- miRNAs
- miRNAs, microRNAs
- ssGSEA, single-sample gene set enrichment analysis
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Affiliation(s)
- Bing-Biao Lin
- Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong 518000, China
| | - Han-Qi Lei
- Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong 518000, China
| | - Hai-Yun Xiong
- Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong 518000, China
| | - Xing Fu
- School of Medicine, Southern University of Science and Technology, 1088 Xueyuan Road, Shenzhen, Guangdong 518055, China
| | - Fu Shi
- Department of Reproductive Medicine Center, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong 518000, China
| | - Xiang-Wei Yang
- Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong 518000, China
| | - Ya-Fei Yang
- Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong 518000, China
| | - Guo-Long Liao
- Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong 518000, China
| | - Yu-Peng Feng
- Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong 518000, China
| | - Dong-Gen Jiang
- Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong 518000, China
| | - Jun Pang
- Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong 518000, China
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Maryam Khorasani, Shahbazi S, Abolhasani M, Shahrokh H, Mahdian R. Expression Profile of MiR-200 Family Members and Their Targets in Prostate Cancer. CYTOL GENET+ 2021. [DOI: 10.3103/s009545272104006x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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STAT5 as a Key Protein of Erythropoietin Signalization. Int J Mol Sci 2021; 22:ijms22137109. [PMID: 34281163 PMCID: PMC8268974 DOI: 10.3390/ijms22137109] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 06/26/2021] [Accepted: 06/29/2021] [Indexed: 12/14/2022] Open
Abstract
Erythropoietin (EPO) acts on multiple tissues through its receptor EPOR, a member of a cytokine class I receptor superfamily with pleiotropic effects. The interaction of EPO and EPOR triggers the activation of several signaling pathways that induce erythropoiesis, including JAK2/STAT5, PI3K/AKT, and MAPK. The canonical EPOR/JAK2/STAT5 pathway is a known regulator of differentiation, proliferation, and cell survival of erythroid progenitors. In addition, its role in the protection of other cells, including cancer cells, is under intense investigation. The involvement of EPOR/JAK2/STAT5 in other processes such as mRNA splicing, cytoskeleton reorganization, and cell metabolism has been recently described. The transcriptomics, proteomics, and epigenetic studies reviewed in this article provide a detailed understanding of EPO signalization. Advances in this area of research may be useful for improving the efficacy of EPO therapy in hematologic disorders, as well as in cancer treatment.
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Aftab M, Poojary SS, Seshan V, Kumar S, Agarwal P, Tandon S, Zutshi V, Das BC. Urine miRNA signature as a potential non-invasive diagnostic and prognostic biomarker in cervical cancer. Sci Rep 2021; 11:10323. [PMID: 33990639 PMCID: PMC8121812 DOI: 10.1038/s41598-021-89388-w] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Accepted: 04/23/2021] [Indexed: 12/21/2022] Open
Abstract
MicroRNAs as cancer biomarkers in serum, plasma, and other body fluids are often used but analysis of miRNA in urine is limited. We investigated the expression of selected miRNAs in the paired urine, serum, cervical scrape, and tumor tissue specimens from the women with cervical precancer and cancer with a view to identify if urine miRNAs could be used as reliable non-invasive biomarkers for an early diagnosis and prognosis of cervical cancer. Expression of three oncomiRs (miR-21, miR-199a, and miR-155-5p) and three tumor suppressors (miR-34a, miR-145, and miR-218) as selected by database search in cervical pre-cancer, cancer, and normal controls including cervical cancer cell lines were analyzed using qRT-PCR. The expression of miRNAs was correlated with various clinicopathological parameters, including HPV infection and survival outcome. We observed a significant overexpression of the oncomiRs and the downregulation of tumor suppressor miRNAs. A combination of miR-145-5p, miR-218-5p, and miR-34a-5p in urine yielded 100% sensitivity and 92.8% specificity in distinguishing precancer and cancer patients from healthy controls and it well correlates with those of serum and tumor tissues. The expression of miR-34a-5p and miR-218-5p were found to be independent prognostic factors for the overall survival of cervical cancer patients. We conclude that the evaluation of the above specific miRNA expression in non-invasive urine samples may serve as a reliable biomarker for early detection and prognosis of cervical cancer.
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Affiliation(s)
- Mehreen Aftab
- Amity Institute of Molecular Medicine & Stem Cell Research (AIMMSCR), Amity University Campus, Sector-125, Noida, Uttar Pradesh, 201313, India
| | - Satish S Poojary
- Amity Institute of Molecular Medicine & Stem Cell Research (AIMMSCR), Amity University Campus, Sector-125, Noida, Uttar Pradesh, 201313, India
| | - Vaishnavi Seshan
- Department of Gynecology and Obstetrics, Safdarjung Hospital, New Delhi, 110029, India
| | - Sachin Kumar
- Depatment of Medical Oncology, Dr. B R Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India
| | - Pallavi Agarwal
- Amity Institute of Molecular Medicine & Stem Cell Research (AIMMSCR), Amity University Campus, Sector-125, Noida, Uttar Pradesh, 201313, India
| | - Simran Tandon
- Amity Institute of Molecular Medicine & Stem Cell Research (AIMMSCR), Amity University Campus, Sector-125, Noida, Uttar Pradesh, 201313, India
| | - Vijay Zutshi
- Department of Gynecology and Obstetrics, Safdarjung Hospital, New Delhi, 110029, India
| | - Bhudev C Das
- Amity Institute of Molecular Medicine & Stem Cell Research (AIMMSCR), Amity University Campus, Sector-125, Noida, Uttar Pradesh, 201313, India.
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Isolation and Quantification of miRNA from the Biomolecular Corona on Mesoporous Silica Nanoparticles. NANOMATERIALS 2021; 11:nano11051196. [PMID: 34062789 PMCID: PMC8147382 DOI: 10.3390/nano11051196] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 04/23/2021] [Accepted: 04/28/2021] [Indexed: 12/21/2022]
Abstract
To understand the factors that control the formation of the biomolecular corona, a systematic study of the adsorption of several miRNAs shown to be important in prostate cancer on amine-functionalized mesoporous silica nanoparticles (MSN-NH2) has been performed. Process parameters including miRNA type, nanoparticle concentration, incubation temperature and incubation time were investigated, as well as the potential competition for adsorption between different miRNA molecules. The influence of proteins and particle PEGylation on miRNA adsorption were also explored. We found that low particle concentrations and physiological temperature both led to increased miRNA adsorption. Adsorption of miRNA was also higher when proteins were present in the same solution; reducing or preventing protein adsorption by PEGylating the MSNs hindered adsorption. Finally, the amount of miRNA adsorbed from human serum by MSN-NH2 was compared to a commercial miRNA purification kit (TaqMan®, Life Technologies, Carlsbad, CA, USA). MSN-NH2 adsorbed six times as much miRNA as the commercial kit, demonstrating higher sensitivity to subtle up- and downregulation of circulating miRNA in the blood of patients.
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Zhang L, Li Y, Wang X, Ping Y, Wang D, Cao Y, Dai Y, Liu W, Tao Z. Five-gene signature associating with Gleason score serve as novel biomarkers for identifying early recurring events and contributing to early diagnosis for Prostate Adenocarcinoma. J Cancer 2021; 12:3626-3647. [PMID: 33995639 PMCID: PMC8120165 DOI: 10.7150/jca.52170] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Accepted: 04/12/2021] [Indexed: 12/14/2022] Open
Abstract
Background: Compared to non-recurrent type, recurrent prostate adenocarcinoma (PCa) is highly fatal, and significantly shortens the survival time of affected patients. Early and accurate laboratory diagnosis is particularly important in identifying patients at high risk of recurrence, necessary for additional systemic intervention. We aimed to develop efficient and accurate diagnostic and prognostic biomarkers for new PCa following radical therapy. Methods: We identified differentially expressed genes (DEGs) and clinicopathological data of PCa patients from Gene Expression Omnibus (GEO) datasets and The Cancer Genome Atlas (TCGA) repositories. We then uncovered the most relevant clinical traits and genes modules associated with PCa prognosis using the Weighted gene correlation network analysis (WGCNA). Univariate Cox regression analysis and multivariate Cox proportional hazards (Cox-PH) models were performed to identify candidate gene signatures related to Disease-Free Interval (DFI). Data for internal and external cohorts were utilized to test and validate the accuracy and clinical utility of the prognostic models. Results: We constructed and validated an accurate and reliable model for predicting the prognosis of PCa using 5 Gleason score-associated gene signatures (ZNF695, CENPA, TROAP, BIRC5 and KIF20A). The ROC and Kaplan-Meier analysis revealed the model was highly accurate in diagnosing and predicting the recurrence and metastases of PCa. The accuracy of the model was validated using the calibration curves based on internal TCGA cohort and external GEO cohort. Using the model, patients could be prognostically stratified in to various groups including TNM classification and Gleason score. Multivariate analysis revealed the model could independently predict the prognosis of PCa patients and its utility was superior to that of clinicopathological characteristics. In addition, we fund the expression of the 5 gene signatures strongly and positively correlated with tumor purity but negatively correlated with infiltration CD8+ T cells to the tumor microenvironment. Conclusions: A 5 gene signatures can accurately be used in the diagnosis and prediction of PCa prognosis. Thus this can guide the treatment and management prostate adenocarcinoma.
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Affiliation(s)
- Lingyu Zhang
- Department of Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China
| | - Yu Li
- Department of Biochemistry and Molecular Biology, Bengbu Medical College, Anhui 233030, China
| | - Xuchu Wang
- Department of Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China
| | - Ying Ping
- Department of Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China
| | - Danhua Wang
- Department of Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China
| | - Ying Cao
- Department of Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China
| | - Yibei Dai
- Department of Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China
| | - Weiwei Liu
- Department of Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China
| | - Zhihua Tao
- Department of Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China
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Yokoi A, Ochiya T. Exosomes and extracellular vesicles: Rethinking the essential values in cancer biology. Semin Cancer Biol 2021; 74:79-91. [PMID: 33798721 DOI: 10.1016/j.semcancer.2021.03.032] [Citation(s) in RCA: 88] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 03/17/2021] [Accepted: 03/28/2021] [Indexed: 02/07/2023]
Abstract
Extracellular vesicles (EVs) such as exosomes are released by all living cells and contain diverse bioactive molecules, including nucleic acids, proteins, lipids, and metabolites. Accumulating evidence of EV-related functions has revealed that these tiny vesicles can mediate specific cell-to-cell communication. Within the tumor microenvironment, diverse cells are actively interacting with their surroundings via EVs facilitating tumor malignancy by regulating malignant cascades including angiogenesis, immune modulation, and metastasis. This review summarizes the recent studies of fundamental understandings of EVs from the aspect of EV heterogeneity and highlights the role of EVs in the various steps from oncogenic to metastatic processes. The recognition of EV subtypes is necessary to identify which pathways can be affected by EVs and which subtypes can be targeted in therapeutic approaches or liquid biopsies.
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Affiliation(s)
- Akira Yokoi
- Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Institute for Advanced Research, Nagoya University, Nagoya, Japan
| | - Takahiro Ochiya
- Department of Molecular and Cellular Medicine, Tokyo Medical University, Tokyo, Japan.
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Zhou L, Wang W, Wang F, Yang S, Hu J, Lu B, Pan Z, Ma Y, Zheng M, Zhou L, Lei S, Song P, Liu P, Lu W, Lu Y. Plasma-derived exosomal miR-15a-5p as a promising diagnostic biomarker for early detection of endometrial carcinoma. Mol Cancer 2021; 20:57. [PMID: 33781255 PMCID: PMC8006369 DOI: 10.1186/s12943-021-01352-4] [Citation(s) in RCA: 99] [Impact Index Per Article: 24.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 03/20/2021] [Indexed: 11/13/2022] Open
Abstract
Endometrial cancer (EC) is a major cause of death among gynecologic malignancies. To improve early detection of EC in patients, we carried out a large plasma-derived exosomal microRNA (miRNA) studies for diagnostic biomarker discovery in EC. Small RNA sequencing was performed to identify candidate exosomal miRNAs as diagnostic biomarkers in 56 plasma samples from healthy subjects and EC patients. These miRNA candidates were further validated in 202 independent plasma samples by droplet digital PCR (ddPCR), 32 pairs of endometrial tumors and adjacent normal tissues by quantitative real-time PCR (qRT-PCR), and matched plasma samples of 12 patients before and after surgery by ddPCR. miR-15a-5p, miR-106b-5p, and miR107 were significantly upregulated in exomes isolated from plasma samples of EC patients compared with healthy subjects. Particularly, miR-15a-5p alone yielded an AUC value of 0.813 to distinguish EC patients with stage I from healthy subjects. The integration of miR-15a-5p and serum tumor markers (CEA and CA125) achieved a higher AUC value of 0.899. There was also a close connection between miR-15a-5p and clinical manifestations in EC patients. Its exosomal expression was not only associated with the depth of muscular infiltration and aggressiveness of EC, but also correlated with levels of reproductive hormones such as TTE and DHEAS. Collectively, plasma-derived exosomal miR-15a-5p is a promising and effective diagnostic biomarker for the early detection of endometrial cancer.
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Affiliation(s)
- Lanyun Zhou
- Department of Gynecologic Oncology, Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Women's Reproductive Health Key Laboratory of Zhejiang Province, Women's Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang, China
| | - Wei Wang
- Department of Clinical Laboratory, Tongde Hospital of Zhejiang Province, Hangzhou, 310006, Zhejiang, China
| | - Fenfen Wang
- Department of Gynecologic Oncology, Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Women's Reproductive Health Key Laboratory of Zhejiang Province, Women's Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang, China
| | - Siqi Yang
- Department of Gynecologic Oncology, Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Women's Reproductive Health Key Laboratory of Zhejiang Province, Women's Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang, China
| | - Jiaqi Hu
- Department of Gynecologic Oncology, Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Women's Reproductive Health Key Laboratory of Zhejiang Province, Women's Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang, China
| | - Bingjian Lu
- Department of Gynecologic Oncology, Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Women's Reproductive Health Key Laboratory of Zhejiang Province, Women's Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang, China
| | - Zimin Pan
- Department of Gynecologic Oncology, Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Women's Reproductive Health Key Laboratory of Zhejiang Province, Women's Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang, China
| | - Yu Ma
- Department of Gynecologic Oncology, Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Women's Reproductive Health Key Laboratory of Zhejiang Province, Women's Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang, China
| | - Mengyue Zheng
- Department of Gynecologic Oncology, Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Women's Reproductive Health Key Laboratory of Zhejiang Province, Women's Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang, China
| | - Liyuan Zhou
- Department of Respiratory Medicine, Sir Run Run Shaw Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang, China
| | - Shufeng Lei
- Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, 215123, Jiangsu, China
| | - Penghong Song
- Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310013, Zhejiang, China
| | - Pengyuan Liu
- Department of Respiratory Medicine, Sir Run Run Shaw Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang, China. .,Cancer center, Zhejiang University, Hangzhou, 310013, Zhejiang, China.
| | - Weiguo Lu
- Department of Gynecologic Oncology, Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Women's Reproductive Health Key Laboratory of Zhejiang Province, Women's Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang, China. .,Cancer center, Zhejiang University, Hangzhou, 310013, Zhejiang, China.
| | - Yan Lu
- Department of Gynecologic Oncology, Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Women's Reproductive Health Key Laboratory of Zhejiang Province, Women's Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang, China. .,Cancer center, Zhejiang University, Hangzhou, 310013, Zhejiang, China.
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Chen Y, Wu T, Zhu Z, Huang H, Zhang L, Goel A, Yang M, Wang X. An integrated workflow for biomarker development using microRNAs in extracellular vesicles for cancer precision medicine. Semin Cancer Biol 2021; 74:134-155. [PMID: 33766650 DOI: 10.1016/j.semcancer.2021.03.011] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 03/13/2021] [Accepted: 03/16/2021] [Indexed: 02/06/2023]
Abstract
EV-miRNAs are microRNA (miRNA) molecules encapsulated in extracellular vesicles (EVs), which play crucial roles in tumor pathogenesis, progression, and metastasis. Recent studies about EV-miRNAs have gained novel insights into cancer biology and have demonstrated a great potential to develop novel liquid biopsy assays for various applications. Notably, compared to conventional liquid biomarkers, EV-miRNAs are more advantageous in representing host-cell molecular architecture and exhibiting higher stability and specificity. Despite various available techniques for EV-miRNA separation, concentration, profiling, and data analysis, a standardized approach for EV-miRNA biomarker development is yet lacking. In this review, we performed a substantial literature review and distilled an integrated workflow encompassing important steps for EV-miRNA biomarker development, including sample collection and EV isolation, EV-miRNA extraction and quantification, high-throughput data preprocessing, biomarker prioritization and model construction, functional analysis, as well as validation. With the rapid growth of "big data", we highlight the importance of efficient mining of high-throughput data for the discovery of EV-miRNA biomarkers and integrating multiple independent datasets for in silico and experimental validations to increase the robustness and reproducibility. Furthermore, as an efficient strategy in systems biology, network inference provides insights into the regulatory mechanisms and can be used to select functionally important EV-miRNAs to refine the biomarker candidates. Despite the encouraging development in the field, a number of challenges still hinder the clinical translation. We finally summarize several common challenges in various biomarker studies and discuss potential opportunities emerging in the related fields.
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Affiliation(s)
- Yu Chen
- Department of Biomedical Sciences, City University of Hong Kong, 31 To Yuen Street, Kowloon Tong, Hong Kong
| | - Tan Wu
- Department of Biomedical Sciences, City University of Hong Kong, 31 To Yuen Street, Kowloon Tong, Hong Kong
| | - Zhongxu Zhu
- Department of Biomedical Sciences, City University of Hong Kong, 31 To Yuen Street, Kowloon Tong, Hong Kong
| | - Hao Huang
- Department of Biomedical Sciences, City University of Hong Kong, 31 To Yuen Street, Kowloon Tong, Hong Kong
| | - Liang Zhang
- Department of Biomedical Sciences, City University of Hong Kong, 31 To Yuen Street, Kowloon Tong, Hong Kong; Tung Biomedical Sciences Centre, City University of Hong Kong, Hong Kong; Key Laboratory of Biochip Technology, Biotech and Health Centre, Shenzhen Research Institute, City University of Hong Kong, Shenzhen, Guangdong Province, China
| | - Ajay Goel
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA, USA
| | - Mengsu Yang
- Department of Biomedical Sciences, City University of Hong Kong, 31 To Yuen Street, Kowloon Tong, Hong Kong; Tung Biomedical Sciences Centre, City University of Hong Kong, Hong Kong; Key Laboratory of Biochip Technology, Biotech and Health Centre, Shenzhen Research Institute, City University of Hong Kong, Shenzhen, Guangdong Province, China
| | - Xin Wang
- Department of Biomedical Sciences, City University of Hong Kong, 31 To Yuen Street, Kowloon Tong, Hong Kong; Tung Biomedical Sciences Centre, City University of Hong Kong, Hong Kong; Key Laboratory of Biochip Technology, Biotech and Health Centre, Shenzhen Research Institute, City University of Hong Kong, Shenzhen, Guangdong Province, China.
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Huang H, Xie S, Gu X, Xiang B, Zhong Z, Huang P, Gao Y, Li P. Higher Circulating miR-199a-5p Indicates Poor Aerobic Exercise Capacity and Associates With Cardiovascular Dysfunction During Chronic Exposure to High Altitude. Front Physiol 2021; 12:587241. [PMID: 33633582 PMCID: PMC7900411 DOI: 10.3389/fphys.2021.587241] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2020] [Accepted: 01/07/2021] [Indexed: 12/14/2022] Open
Abstract
Background Hypoxia-induced decline in exercise capacity is ubiquitous among lowlanders who immigrated to high altitudes, which severely reduces their work efficiency and quality of life. Although studies have revealed that hypoxia-induced cardiovascular dysfunction limits exercise capacity at high altitudes, the mechanisms have not been well explored at the molecular level. miR-199a-5p is hypoxia-sensitive and serves as an important regulator in cardiovascular pathophysiology. However, whether miR-199a-5p is involved in cardiovascular dysfunction at high altitudes and contributes to subsequent reductions in exercise capacity remains unknown. Thus, this study aimed at exploring these relationships in a high altitude population. Methods A total of 175 lowlanders who had immigrated to an altitude of 3,800 m 2 years previously participated in the present study. The level of plasma miR-199a-5p and the concentration of serum myocardial enzymes were detected by qRT-PCR and ELISA, respectively. Indices of cardiovascular function were examined by echocardiography. The exercise capacity was evaluated by Cooper’s 12-min run test and the Harvard Step Test. Furthermore, we explored the biological functions of miR-199a-5p with silico analysis and a biochemical test. Results The level of miR-199a-5p was significantly higher in individuals with poor exercise capacity at 3,800 m, compared with those with good exercise capacity (p < 0.001). miR-199a-5p accurately identified individuals with poor exercise capacity (AUC = 0.752, p < 0.001). The level of miR-199a-5p was positively correlated with cardiovascular dysfunction indices (all, p < 0.001). Furthermore, miR-199a-5p was involved in the oxidative stress process. Conclusion In this study, we reported for the first time that the level of circulating miR-199a-5p was positively associated with exercise capacity during chronic hypoxia at high altitudes. Moreover, higher miR-199a-5p was involved in hypoxia-induced cardiovascular dysfunctions, thus contributing to poorer exercise endurance at high altitudes.
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Affiliation(s)
- He Huang
- Department of High Altitude Operational Medicine, College of High Altitude Military Medicine, Army Medical University (Third Military Medical University), Chongqing, China.,College of High Altitude Military Medicine, Institute of Medicine and Equipment for High Altitude Region, Army Medical University (Third Military Medical University), Chongqing, China.,Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, China.,Key Laboratory of High Altitude Medicine, PLA, Chongqing, China
| | - Shenwei Xie
- Shigatse Branch, Second Affiliated Hospital (Xinqiao Hospital) of Army Medical University (Third Military Medical University), Tibet, China
| | - Xiaolan Gu
- Department of Infectious Diseases, First Affiliated Hospital of Army Medical University (Third Military Medical University), Chongqing, China
| | - Bin Xiang
- Department of High Altitude Operational Medicine, College of High Altitude Military Medicine, Army Medical University (Third Military Medical University), Chongqing, China.,Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, China.,Key Laboratory of High Altitude Medicine, PLA, Chongqing, China
| | - Zhifeng Zhong
- Department of High Altitude Operational Medicine, College of High Altitude Military Medicine, Army Medical University (Third Military Medical University), Chongqing, China.,Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, China.,Key Laboratory of High Altitude Medicine, PLA, Chongqing, China
| | - Pei Huang
- Department of High Altitude Operational Medicine, College of High Altitude Military Medicine, Army Medical University (Third Military Medical University), Chongqing, China.,Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, China.,Key Laboratory of High Altitude Medicine, PLA, Chongqing, China
| | - Yuqi Gao
- College of High Altitude Military Medicine, Institute of Medicine and Equipment for High Altitude Region, Army Medical University (Third Military Medical University), Chongqing, China.,Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, China.,Key Laboratory of High Altitude Medicine, PLA, Chongqing, China
| | - Peng Li
- Department of High Altitude Operational Medicine, College of High Altitude Military Medicine, Army Medical University (Third Military Medical University), Chongqing, China.,Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, China.,Key Laboratory of High Altitude Medicine, PLA, Chongqing, China
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Dell'Olio F, Su J, Huser T, Sottile V, Cortés-Hernández LE, Alix-Panabières C. Photonic technologies for liquid biopsies: recent advances and open research challenges. LASER & PHOTONICS REVIEWS 2021; 15:2000255. [PMID: 35360260 PMCID: PMC8966629 DOI: 10.1002/lpor.202000255] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Indexed: 05/15/2023]
Abstract
The recent development of sophisticated techniques capable of detecting extremely low concentrations of circulating tumor biomarkers in accessible body fluids, such as blood or urine, could contribute to a paradigm shift in cancer diagnosis and treatment. By applying such techniques, clinicians can carry out liquid biopsies, providing information on tumor presence, evolution, and response to therapy. The implementation of biosensing platforms for liquid biopsies is particularly complex because this application domain demands high selectivity/specificity and challenging limit-of-detection (LoD) values. The interest in photonics as an enabling technology for liquid biopsies is growing owing to the well-known advantages of photonic biosensors over competing technologies in terms of compactness, immunity to external disturbance, and ultra-high spatial resolution. Some encouraging experimental results in the field of photonic devices and systems for liquid biopsy have already been achieved by using fluorescent labels and label-free techniques and by exploiting super-resolution microscopy, surface plasmon resonance, surface-enhanced Raman scattering, and whispering gallery mode resonators. This paper critically reviews the current state-of-the-art, starting from the requirements imposed by the detection of the most common circulating biomarkers. Open research challenges are considered together with competing technologies, and the most promising paths of improvement are discussed for future applications.
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Affiliation(s)
- Francesco Dell'Olio
- Department of Electrical and Information Engineering, Polytechnic University of Bari, 70125, Italy
| | - Judith Su
- Department of Biomedical Engineering, College of Optical Sciences, and BIO5 Institute, University of Arizona, 85721, USA
| | - Thomas Huser
- Biomolecular Photonics, Department of Physics, University of Bielefeld, 33615 Germany
| | - Virginie Sottile
- Department of Molecular Medicine, University of Pavia, 27100, Italy
| | | | - Catherine Alix-Panabières
- Laboratory of Rare Human Circulating Cells (LCCRH), University Medical Center of Montpellier, 34093 CEDEX 5, France
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Wang Y, Fang YX, Dong B, Du X, Wang J, Wang X, Gao WQ, Xue W. Discovery of extracellular vesicles derived miR-181a-5p in patient's serum as an indicator for bone-metastatic prostate cancer. Theranostics 2021; 11:878-892. [PMID: 33391510 PMCID: PMC7738844 DOI: 10.7150/thno.49186] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Accepted: 10/20/2020] [Indexed: 12/20/2022] Open
Abstract
Purpose: To identify extracellular vesicle (EV)-delivered microRNAs in the patient's serum as indicators for bone-metastatic prostate cancer. Methods: First, the profiling change of serum EV-delivered miRNAs in patients with either benign prostatic hyperplasia (BPH), non-bone metastatic prostate cancer or bone-metastatic prostate cancer was detected by microRNA deep sequencing assay and microRNA-chip array assay, respectively. Second, the candidates were further confirmed using TaqMan microRNA assay in two independent validation cohorts of total 176 patients with either BPH, non-bone metastatic prostate cancer or bone metastatic prostate cancer to seek the most valuable microRNA(s). Results: Through microRNA deep sequencing and microRNA-chip array, we found 4 prospective EV-delivered miRNAs including miR-181a-5p with significantly upregulated expression in bone metastatic groups than in non-bone metastatic prostate cancer groups (p < 0.05). In the validation cohorts, logistic regression analysis was performed to evaluate the diagnostic association of candidates with bone metastasis, which indicated that miR-181a-5p was significantly associated with bone metastatic prostate cancer. Furthermore, accuracy estimate of each candidate for the diagnosis of bone metastatic prostate cancer was quantified using the area under the receiver-operating characteristic curve (AUC), which identified miR-181a-5p as the best biomarker with the AUCs of 85.6% for diagnosis of prostate cancer and 73.8% for diagnosis of bone metastatic prostate cancer. Conclusion: EV-delivered miR-181a-5p from patient's serum is a promising diagnostic biomarker for bone metastatic prostate cancer.
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Xing Y, Cheng Z, Wang R, Lv C, James TD, Yu F. Analysis of extracellular vesicles as emerging theranostic nanoplatforms. Coord Chem Rev 2020. [DOI: 10.1016/j.ccr.2020.213506] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Liu T, Du LT, Wang YS, Gao SY, Li J, Li PL, Sun ZW, Binang H, Wang CX. Development of a Novel Serum Exosomal MicroRNA Nomogram for the Preoperative Prediction of Lymph Node Metastasis in Esophageal Squamous Cell Carcinoma. Front Oncol 2020; 10:573501. [PMID: 33123480 PMCID: PMC7573187 DOI: 10.3389/fonc.2020.573501] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 08/26/2020] [Indexed: 12/13/2022] Open
Abstract
Preoperative prediction of lymph node (LN) metastasis is accepted as a crucial independent risk factor for treatment decision-making for esophageal squamous cell carcinoma (ESCC) patients. Our study aimed to establish a non-invasive nomogram to identify LN metastasis preoperatively in ESCC patients. Construction of the nomogram involved three sequential phases with independent patient cohorts. In the discovery phase (N = 20), LN metastasis-associated microRNAs (miRNAs) were selected from next-generation sequencing (NGS) assay of human ESCC serum exosome samples. In the training phase (N = 178), a nomogram that incorporated exosomal miRNA model and clinicopathologic was developed by multivariate logistic regression analysis to preoperatively predict LN status. In the validation phase (n = 188), we validated the predicted nomogram's calibration, discrimination, and clinical usefulness. Four differently expressed miRNAs (chr 8-23234-3p, chr 1-17695-5p, chr 8-2743-5p, and miR-432-5p) were tested and selected in the serum exosome samples from ESCC patients who have or do not have LN metastasis. Subsequently, an optimized four-exosomal miRNA model was constructed and validated in the clinical samples, which could effectively identify ESCC patients with LN metastasis, and was significantly superior to preoperative computed tomography (CT) report. In addition, a clinical nomogram consisting of the four-exosomal miRNA model and CT report was established in training cohort, which showed high predictive value in both training and validation cohorts [area under the receiver operating characteristic curve (AUC): 0.880 and 0.869, respectively]. The Hosmer–Lemeshow test and decision curve analysis implied the nomogram's clinical applicability. Our novel non-invasive nomogram is a robust prediction tool with promising clinical potential for preoperative LN metastasis prediction of ESCC patients, especially in T1 stage.
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Affiliation(s)
- Tong Liu
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Lu-Tao Du
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.,Shandong Engineering & Technology Research Center for Tumor Marker Detection, Jinan, China.,Shandong Provincial Clinical Medicine Research Center for Clinical Laboratory, Jinan, China
| | - Yun-Shan Wang
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.,Shandong Engineering & Technology Research Center for Tumor Marker Detection, Jinan, China.,Shandong Provincial Clinical Medicine Research Center for Clinical Laboratory, Jinan, China
| | - Shan-Yu Gao
- Department of Surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Juan Li
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.,Shandong Engineering & Technology Research Center for Tumor Marker Detection, Jinan, China.,Shandong Provincial Clinical Medicine Research Center for Clinical Laboratory, Jinan, China
| | - Pei-Long Li
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.,Shandong Engineering & Technology Research Center for Tumor Marker Detection, Jinan, China.,Shandong Provincial Clinical Medicine Research Center for Clinical Laboratory, Jinan, China
| | - Zhao-Wei Sun
- Department of Surgery, The Affiliated Hospital of Medical College Qingdao University, Qingdao, China
| | - Helen Binang
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Chuan-Xin Wang
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.,Shandong Engineering & Technology Research Center for Tumor Marker Detection, Jinan, China.,Shandong Provincial Clinical Medicine Research Center for Clinical Laboratory, Jinan, China
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Zhang YH, Jin M, Li J, Kong X. Identifying circulating miRNA biomarkers for early diagnosis and monitoring of lung cancer. Biochim Biophys Acta Mol Basis Dis 2020; 1866:165847. [DOI: 10.1016/j.bbadis.2020.165847] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2020] [Revised: 04/28/2020] [Accepted: 05/19/2020] [Indexed: 02/09/2023]
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Rahat B, Ali T, Sapehia D, Mahajan A, Kaur J. Circulating Cell-Free Nucleic Acids as Epigenetic Biomarkers in Precision Medicine. Front Genet 2020; 11:844. [PMID: 32849827 PMCID: PMC7431953 DOI: 10.3389/fgene.2020.00844] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Accepted: 07/13/2020] [Indexed: 12/20/2022] Open
Abstract
The circulating cell-free nucleic acids (ccfNAs) are a mixture of single- or double-stranded nucleic acids, released into the blood plasma/serum by different tissues via apoptosis, necrosis, and secretions. Under healthy conditions, ccfNAs originate from the hematopoietic system, whereas under various clinical scenarios, the concomitant tissues release ccfNAs into the bloodstream. These ccfNAs include DNA, RNA, microRNA (miRNA), long non-coding RNA (lncRNA), fetal DNA/RNA, and mitochondrial DNA/RNA, and act as potential biomarkers in various clinical conditions. These are associated with different epigenetic modifications, which show disease-related variations and so finding their role as epigenetic biomarkers in clinical settings. This field has recently emerged as the latest advance in precision medicine because of its clinical relevance in diagnostic, prognostic, and predictive values. DNA methylation detected in ccfDNA has been widely used in personalized clinical diagnosis; furthermore, there is also the emerging role of ccfRNAs like miRNA and lncRNA as epigenetic biomarkers. This review focuses on the novel approaches for exploring ccfNAs as epigenetic biomarkers in personalized clinical diagnosis and prognosis, their potential as therapeutic targets and disease progression monitors, and reveals the tremendous potential that epigenetic biomarkers present to improve precision medicine. We explore the latest techniques for both quantitative and qualitative detection of epigenetic modifications in ccfNAs. The data on epigenetic modifications on ccfNAs are complex and often milieu-specific posing challenges for its understanding. Artificial intelligence and deep networks are the novel approaches for decoding complex data and providing insight into the decision-making in precision medicine.
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Affiliation(s)
- Beenish Rahat
- National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States
| | - Taqveema Ali
- Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Divika Sapehia
- Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Aatish Mahajan
- Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Jyotdeep Kaur
- Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Sereno M, Videira M, Wilhelm I, Krizbai IA, Brito MA. miRNAs in Health and Disease: A Focus on the Breast Cancer Metastatic Cascade towards the Brain. Cells 2020; 9:E1790. [PMID: 32731349 PMCID: PMC7463742 DOI: 10.3390/cells9081790] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Revised: 07/20/2020] [Accepted: 07/21/2020] [Indexed: 12/11/2022] Open
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs that mainly act by binding to target genes to regulate their expression. Due to the multitude of genes regulated by miRNAs they have been subject of extensive research in the past few years. This state-of-the-art review summarizes the current knowledge about miRNAs and illustrates their role as powerful regulators of physiological processes. Moreover, it highlights their aberrant expression in disease, including specific cancer types and the differential hosting-metastases preferences that influence several steps of tumorigenesis. Considering the incidence of breast cancer and that the metastatic disease is presently the major cause of death in women, emphasis is put in the role of miRNAs in breast cancer and in the regulation of the different steps of the metastatic cascade. Furthermore, we depict their involvement in the cascade of events underlying breast cancer brain metastasis formation and development. Collectively, this review shall contribute to a better understanding of the uniqueness of the biologic roles of miRNAs in these processes, to the awareness of miRNAs as new and reliable biomarkers and/or of therapeutic targets, which can change the landscape of a poor prognosis and low survival rates condition of advanced breast cancer patients.
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Affiliation(s)
- Marta Sereno
- Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisbon, Portugal, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal; (M.S.); (M.V.)
| | - Mafalda Videira
- Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisbon, Portugal, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal; (M.S.); (M.V.)
- Department of Galenic Pharmacy and Pharmaceutical Technology, Faculdade de Farmácia, Universidade de Lisboa, Lisbon, Portugal, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal
| | - Imola Wilhelm
- Institute of Biophysics, Biological Research Centre, Szeged, Hungary, Temesvári krt. 62, 6726 Szeged, Hungary; (I.W.); (I.A.K.)
- Institute of Life Sciences, Vasile Goldiş Western University of Arad, Arad, Romania, Str. Liviu Rebreanu 86, 310414 Arad, Romania
| | - István A. Krizbai
- Institute of Biophysics, Biological Research Centre, Szeged, Hungary, Temesvári krt. 62, 6726 Szeged, Hungary; (I.W.); (I.A.K.)
- Institute of Life Sciences, Vasile Goldiş Western University of Arad, Arad, Romania, Str. Liviu Rebreanu 86, 310414 Arad, Romania
| | - Maria Alexandra Brito
- Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisbon, Portugal, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal; (M.S.); (M.V.)
- Department of Biochemistry and Human Biology, Faculdade de Farmácia, Universidade de Lisboa, Lisbon, Portugal, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal
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