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Cao LM, Qiu YZ, Li ZZ, Wang GR, Xiao Y, Luo HY, Liu B, Wu Q, Bu LL. Extracellular Vesicles: Hermes between cancers and lymph nodes. Cancer Lett 2025; 623:217735. [PMID: 40268131 DOI: 10.1016/j.canlet.2025.217735] [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: 02/05/2025] [Revised: 04/16/2025] [Accepted: 04/19/2025] [Indexed: 04/25/2025]
Abstract
Cancer is one of the main causes of death and a major obstacle to increasing life expectancy in all countries of the world. Lymph node metastasis (LNM) of in cancer patients indicates poor prognosis and it is an important indication to determine the therapeutic regime. Therefore, more attention should be given to the molecular mechanics of tumor lymphangiogenesis and LNM. Extracellular vesicles (EVs) are nanoscale cargo-bearing membrane vesicles that can serve as key mediators for the intercellular communication. Like Hermes, the messenger of the Greek gods, EVs can be secreted by tumor cells to regulate the LNM process. Many evidence has proved the clinical correlation between EVs and LNM in various cancer types. EVs plays an active role in the process of metastasis by expressing its connotative molecules, including proteins, nucleic acids, and metabolites. However, the clear role of EVs in the process of cancer LNM has not been thoroughly studied yet. In this review, we will summarize the clinical and mechanical findings of EVs regulating role on cancer LNM, and discuss the advanced modification of the research proposal. We propose the "PUMP" principle of EVs in LNM, including Preparation, Unleash, Migration, and Planting.
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Affiliation(s)
- Lei-Ming Cao
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China
| | - Yu-Zhong Qiu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China
| | - Zi-Zhan Li
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China
| | - Guang-Rui Wang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China
| | - Yao Xiao
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China
| | - Han-Yue Luo
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China
| | - Bing Liu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China; Department of Oral & Maxillofacial Head Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China
| | - Qiuji Wu
- Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behavior, Hubei Provincial Clinical Research Center for Cancer, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
| | - Lin-Lin Bu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China; Department of Oral & Maxillofacial Head Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China.
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Hut AR, Boia ER, Para D, Iovanescu G, Horhat D, Mikša L, Chiriac M, Galant R, Motofelea AC, Balica NC. Laryngeal Cancer in the Modern Era: Evolving Trends in Diagnosis, Treatment, and Survival Outcomes. J Clin Med 2025; 14:3367. [PMID: 40429363 DOI: 10.3390/jcm14103367] [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: 04/12/2025] [Revised: 05/08/2025] [Accepted: 05/09/2025] [Indexed: 05/29/2025] Open
Abstract
Background/Objectives: Laryngeal cancer (LC), predominantly squamous cell carcinoma (SCC), represents a considerable health burden worldwide. Tumour subsite heterogeneity (supraglottic, glottic, subglottic) influences clinical behavior and outcomes. This review synthesizes current knowledge on epidemiology, risk factors, diagnostics, histological variants, biomarkers, treatment modalities, and survival. Results: This narrative review synthesizes current literature on the epidemiology, risk factors, diagnosis, histological variants, biomarkers, and prognosis of LC. The review highlights the critical influence of tumour sites (supraglottic, glottic, subglottic) on metastatic patterns and survival. Key risk factors of LC include tobacco and alcohol use, human papillomavirus (HPV) infection, and occupational exposures. The diagnostic process encompasses clinical examination, endoscopy, biopsy, and imaging. Several biomarkers that aid in diagnosis, treatment plan determination, and prognosis prediction have been established. These biomarkers include long noncoding RNAs, cell cycle regulators, apoptosis regulators, oncogenes, tumour suppressor genes, growth factor pathway components, angiogenic factors, structural proteins, sex hormone receptors, and immunological markers. Current treatment modalities range from organ-preserving surgery and radiotherapy to combined chemoradiotherapy and total laryngectomy. Finally, survival data are presented and stratified by stage and subsite. Conclusions: The review underscores the need for a multidisciplinary approach to LC management, integrating clinical, pathological, and molecular information to optimize patient outcomes.
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Affiliation(s)
- Alexandru-Romulus Hut
- Department of Doctoral Studies, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
- ENT Department, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
| | - Eugen Radu Boia
- ENT Department, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
- ENT Department, Emergency City Hospital, 300254 Timisoara, Romania
| | - Diana Para
- Department of Doctoral Studies, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
| | - Gheorghe Iovanescu
- ENT Department, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
| | - Delia Horhat
- ENT Department, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
- ENT Department, Emergency City Hospital, 300254 Timisoara, Romania
| | - Loredan Mikša
- ENT Department, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
| | - Maria Chiriac
- ENT Department, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
| | - Raphaël Galant
- Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, 20 Rue Leblanc, 75015 Paris, France
| | - Alexandru Catalin Motofelea
- Department of Doctoral Studies, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
- Center for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Nicolae Constantin Balica
- ENT Department, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
- ENT Department, Emergency City Hospital, 300254 Timisoara, Romania
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Tandon R, Srivastava N. Unravelling exosome paradigm: Therapeutic, diagnostic and theranostics application and regulatory consideration. Life Sci 2025; 366-367:123472. [PMID: 39956185 DOI: 10.1016/j.lfs.2025.123472] [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: 07/21/2024] [Revised: 01/13/2025] [Accepted: 02/13/2025] [Indexed: 02/18/2025]
Abstract
In the recent decade, extracellular vesicles (EVs) have been released from nearly all the kingdoms, modulating intercellular communication and maintaining the human body's homeostasis by regulating different cellular processes. Among EVs, exosomes are the emerging field in biopharmaceuticals. They have lipid bilayer ranging from 30 to 150 nm in size and encompass DNA, RNA, protein lipids, etc. Their sources are widespread, easy to acquire, and cost-effective in manufacturing. This review focuses on the detailed classification of exosomes existing in nature, knowledge and application of omics, therapeutic, diagnostic and theranostic application of exosomes. It covers diseases such as cancer, infectious diseases (viral, bacterial, fungal infections), neurodegenerative diseases, metabolic diseases, lifestyle diseases (diabetes, cardiovascular, gastric disorder (IBD)), autoimmune disorders and their biodistribution. This article unfolds the recent progress in the exosomes arena and covers all the regulatory considerations (FDA, EMA, and other nations) involved with it. Moreover, a detailed discussion about clinical trials and its manifestation with exosomes and challenges associated with their isolation procedures, reproducibility, and safety concerns.
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Affiliation(s)
- Reetika Tandon
- Department of Biotechnology, National Institute of Pharmaceutical Education and Research-Raebareli, Lucknow 226002, India
| | - Nidhi Srivastava
- Department of Biotechnology, National Institute of Pharmaceutical Education and Research-Raebareli, Lucknow 226002, India.
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Márton É, Varga A, Domoszlai D, Buglyó G, Balázs A, Penyige A, Balogh I, Nagy B, Szilágyi M. Non-Coding RNAs in Cancer: Structure, Function, and Clinical Application. Cancers (Basel) 2025; 17:579. [PMID: 40002172 PMCID: PMC11853212 DOI: 10.3390/cancers17040579] [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: 11/15/2024] [Revised: 02/04/2025] [Accepted: 02/06/2025] [Indexed: 02/27/2025] Open
Abstract
We are on the brink of a paradigm shift in both theoretical and clinical oncology. Genomic and transcriptomic profiling, alongside personalized approaches that account for individual patient variability, are increasingly shaping discourse. Discussions on the future of personalized cancer medicine are mainly dominated by the potential of non-coding RNAs (ncRNAs), which play a prominent role in cancer progression and metastasis formation by regulating the expression of oncogenic or tumor suppressor proteins at transcriptional and post-transcriptional levels; furthermore, their cell-free counterparts might be involved in intercellular communication. Non-coding RNAs are considered to be promising biomarker candidates for early diagnosis of cancer as well as potential therapeutic agents. This review aims to provide clarity amidst the vast body of literature by focusing on diverse species of ncRNAs, exploring the structure, origin, function, and potential clinical applications of miRNAs, siRNAs, lncRNAs, circRNAs, snRNAs, snoRNAs, eRNAs, paRNAs, YRNAs, vtRNAs, and piRNAs. We discuss molecular methods used for their detection or functional studies both in vitro and in vivo. We also address the challenges that must be overcome to enter a new era of cancer diagnosis and therapy that will reshape the future of oncology.
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Affiliation(s)
- Éva Márton
- Department of Human Genetics, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary; (É.M.); (A.V.); (D.D.); (G.B.); (A.P.); (I.B.); (B.N.)
| | - Alexandra Varga
- Department of Human Genetics, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary; (É.M.); (A.V.); (D.D.); (G.B.); (A.P.); (I.B.); (B.N.)
| | - Dóra Domoszlai
- Department of Human Genetics, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary; (É.M.); (A.V.); (D.D.); (G.B.); (A.P.); (I.B.); (B.N.)
| | - Gergely Buglyó
- Department of Human Genetics, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary; (É.M.); (A.V.); (D.D.); (G.B.); (A.P.); (I.B.); (B.N.)
| | - Anita Balázs
- Department of Integrative Health Sciences, Institute of Health Sciences, Faculty of Health Sciences, University of Debrecen, H-4032 Debrecen, Hungary;
| | - András Penyige
- Department of Human Genetics, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary; (É.M.); (A.V.); (D.D.); (G.B.); (A.P.); (I.B.); (B.N.)
| | - István Balogh
- Department of Human Genetics, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary; (É.M.); (A.V.); (D.D.); (G.B.); (A.P.); (I.B.); (B.N.)
- Division of Clinical Genetics, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
| | - Bálint Nagy
- Department of Human Genetics, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary; (É.M.); (A.V.); (D.D.); (G.B.); (A.P.); (I.B.); (B.N.)
| | - Melinda Szilágyi
- Department of Human Genetics, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary; (É.M.); (A.V.); (D.D.); (G.B.); (A.P.); (I.B.); (B.N.)
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Banta A, Bratosin F, Golu I, Toma AO, Domuta EM. A Systematic Review of Circulating miRNAs Validated by Multiple Independent Studies in Laryngeal Cancer. Diagnostics (Basel) 2025; 15:394. [PMID: 39941323 PMCID: PMC11817663 DOI: 10.3390/diagnostics15030394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Revised: 02/04/2025] [Accepted: 02/04/2025] [Indexed: 02/16/2025] Open
Abstract
Background and Objectives: Laryngeal squamous cell carcinoma (LSCC) is a common head and neck cancer with significant morbidity and mortality. Circulating microRNAs (miRNAs) have emerged as promising non-invasive biomarkers for cancer diagnosis and prognosis. This systematic review aims to identify circulating miRNAs associated with LSCC, emphasizing those validated by at least two independent studies to improve reliability and clinical applicability. Methods: An extensive literature search was performed in the PubMed, Scopus, and Web of Science databases up to October 2024, using keywords related to LSCC and circulating miRNAs. Studies involving human participants that provided quantitative data on circulating miRNA expression levels and their clinical correlations were included. Data extraction and quality assessment were conducted following standardized protocols, highlighting miRNAs reported in multiple studies. Results: Nine high-quality studies encompassing 660 patients with LSCC and 212 controls were included. Several miRNAs were consistently identified across these studies. miR-21-5p was upregulated in four studies and associated with advanced disease stages, lymph node metastasis, and decreased survival rates. miR-125b-5p and miR-126-3p were consistently downregulated, linked to advanced clinical stages and poor tumor differentiation. miR-27a-3p was upregulated in two studies and correlated with poor prognosis, promoting LSCC progression by targeting Smad4. Additionally, miR-33a-5p was identified as a potential diagnostic biomarker with high sensitivity and specificity. These miRNAs show potential as non-invasive biomarkers for the diagnosis and prognosis of LSCC. Conclusions: This systematic review highlights specific circulating miRNAs-particularly miR-21-5p, miR-125b-5p, miR-126-3p, miR-27a-3p, and miR-33a-5p-as promising biomarkers for LSCC. The consistent findings across independent studies emphasize their potential clinical utility in early detection, prognostic assessment, and therapeutic targeting. However, further validation in larger and more diverse populations, along with the standardization of detection methods, is necessary before these biomarkers can be implemented in clinical practice.
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Affiliation(s)
- Andreea Banta
- Doctoral School, Department of General Medicine, “Victor Babes” University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania;
| | - Felix Bratosin
- Department of Infectious Disease, “Victor Babes” University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania;
| | - Ioana Golu
- Department of Internal Medicine II, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
- University Clinic of Endocrinology, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
- Center for Molecular Research in Nephrology and Vascular Disease, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Square 2, 300041 Timisoara, Romania
| | - Ana-Olivia Toma
- Discipline of Dermatology, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania;
| | - Eugenia Maria Domuta
- Department of Surgery, Faculty of Medicine and Pharmacy, University of Oradea, Piata 1 Decembrie 10, 410073 Oradea, Romania;
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Ma L, Guo H, Zhao Y, Liu Z, Wang C, Bu J, Sun T, Wei J. Liquid biopsy in cancer current: status, challenges and future prospects. Signal Transduct Target Ther 2024; 9:336. [PMID: 39617822 PMCID: PMC11609310 DOI: 10.1038/s41392-024-02021-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Revised: 09/10/2024] [Accepted: 10/14/2024] [Indexed: 12/06/2024] Open
Abstract
Cancer has a high mortality rate across the globe, and tissue biopsy remains the gold standard for tumor diagnosis due to its high level of laboratory standardization, good consistency of results, relatively stable samples, and high accuracy of results. However, there are still many limitations and drawbacks in the application of tissue biopsy in tumor. The emergence of liquid biopsy provides new ideas for early diagnosis and prognosis of tumor. Compared with tissue biopsy, liquid biopsy has many advantages in the diagnosis and treatment of various types of cancer, including non-invasive, quickly and so on. Currently, the application of liquid biopsy in tumor detection has received widely attention. It is now undergoing rapid progress, and it holds significant potential for future applications. Around now, liquid biopsies encompass several components such as circulating tumor cells, circulating tumor DNA, exosomes, microRNA, circulating RNA, tumor platelets, and tumor endothelial cells. In addition, advances in the identification of liquid biopsy indicators have significantly enhanced the possibility of utilizing liquid biopsies in clinical settings. In this review, we will discuss the application, advantages and challenges of liquid biopsy in some common tumors from the perspective of diverse systems of tumors, and look forward to its future development prospects in the field of cancer diagnosis and treatment.
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Affiliation(s)
- Liwei Ma
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
- Key Clinical Laboratory of Henan province, Zhengzhou, Henan, China.
| | - Huiling Guo
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Key Clinical Laboratory of Henan province, Zhengzhou, Henan, China
| | - Yunxiang Zhao
- Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Zhibo Liu
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Key Clinical Laboratory of Henan province, Zhengzhou, Henan, China
| | - Chenran Wang
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Key Clinical Laboratory of Henan province, Zhengzhou, Henan, China
| | - Jiahao Bu
- Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Ting Sun
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
- Key Clinical Laboratory of Henan province, Zhengzhou, Henan, China.
| | - Jianwei Wei
- Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
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Chatterjee M, Gupta S, Nag S, Rehman I, Parashar D, Maitra A, Das K. Circulating Extracellular Vesicles: An Effective Biomarker for Cancer Progression. FRONT BIOSCI-LANDMRK 2024; 29:375. [PMID: 39614441 DOI: 10.31083/j.fbl2911375] [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: 08/01/2024] [Revised: 08/28/2024] [Accepted: 09/10/2024] [Indexed: 12/01/2024]
Abstract
Extracellular vesicles (EVs), the ubiquitous part of human biology, represent a small heterogenous, membrane-enclosed body that contains a diverse payload including genetic materials in the form of DNA, RNAs, small non-coding RNAs, etc. mostly mirroring their source of origin. Since, a vast majority of research has been conducted on how nucleic acids, proteins, lipids, and metabolites, associated with EVs can be effectively utilized to identify disease progression and therapeutic responses in cancer patients, EVs are increasingly being touted as valuable and reliable identifiers of cancer biomarkers in liquid biopsies. However, the lack of comprehensive clinical validation and effective standardization protocols severely limits its applications beyond the laboratories. The present review focuses on understanding the role of circulating EVs in different cancers and how they could potentially be treated as cancer biomarkers, typically due to the presence of bioactive molecules such as small non-coding RNAs, RNAs, DNA, proteins, etc., and their utilization for fine-tuning therapies. Here, we provide a brief general biology of EVs including their classification and subsequently discuss the source of circulatory EVs, the role of their associated payload as biomarkers, and how different cancers affect the level of circulatory EVs population.
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Affiliation(s)
- Madhura Chatterjee
- Biotechnology Research and Innovation Council-National Institute of Biomedical Genomics, 741251 Kalyani, India
| | - Saurabh Gupta
- Department of Biotechnology, GLA University, 281406 Mathura, India
| | - Sayoni Nag
- Department of Biotechnology, Brainware University, 700125 Barasat, India
| | - Ishita Rehman
- Department of Biotechnology, The Neotia University, 743368 Parganas, India
| | - Deepak Parashar
- Department of Medicine, Division of Hematology & Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
| | - Arindam Maitra
- Biotechnology Research and Innovation Council-National Institute of Biomedical Genomics, 741251 Kalyani, India
| | - Kaushik Das
- Biotechnology Research and Innovation Council-National Institute of Biomedical Genomics, 741251 Kalyani, India
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Nedaeinia R, Najafgholian S, Salehi R, Goli M, Ranjbar M, Nickho H, Haghjooy Javanmard S, A Ferns G, Manian M. The role of cancer-associated fibroblasts and exosomal miRNAs-mediated intercellular communication in the tumor microenvironment and the biology of carcinogenesis: a systematic review. Cell Death Discov 2024; 10:380. [PMID: 39187523 PMCID: PMC11347635 DOI: 10.1038/s41420-024-02146-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 07/24/2024] [Accepted: 08/12/2024] [Indexed: 08/28/2024] Open
Abstract
CAFs (cancer-associated fibroblasts) are highly flexible cells of the cancer microenvironment. They produce the extracellular matrix (ECM) constituents that form the structure of the tumor stroma but are also a source of metabolites, growth factors, chemokines, and exosomes that impact every aspect of the tumor, including its response to treatment. It is believed that exosomal miRNAs facilitate intercellular signaling, which is essential for the development of cancer. The role of miRNAs and CAFs in the tumor microenvironment (TME) and carcinogenesis is reviewed in this paper. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020 guidelines were used to perform a systematic review. Several databases, including Web of Science, Medline, Embase, Cochrane Library, and Scopus, were searched using the following keywords: CAFs, CAF, cancer-associated fibroblasts, stromal fibroblasts, miRNA, exosomal miRNAs, exosome and similar terms. We identified studies investigating exosomal miRNAs and CAFs in the TME and their role in carcinogenesis. A total of 12,572 papers were identified. After removing duplicates (n = 3803), 8774 articles were screened by title and abstract. Of these, 421 were excluded from further analysis. It has been reported that if exosomal miRNAs in CAFs are not functioning correctly, this may influence the secretory phenotype of tip cells and contribute to increased tumor invasiveness, tumor spread, decreased treatment efficacy, and a poorer prognosis. Under their influence, normal fibroblasts (NFs) are transformed into CAFs. Furthermore, they participate in metabolic reprogramming, which allows for fast proliferation of the cancer cell population, adaptation to growing energy demands, and the capacity to avoid immune system identification.
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Affiliation(s)
- Reza Nedaeinia
- Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Simin Najafgholian
- Department of Emergency Medicine, School of Medicine, Valiasr Hospital, Arak University of Medical Sciences, Arak, Iran
| | - Rasoul Salehi
- Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad Goli
- Department of Food Science and Technology, Laser and Biophotonics in Biotechnologies Research Center, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan, Iran
| | - Maryam Ranjbar
- Advanced Materials Research Center, Department of Materials Engineering, Najafabad Branch, Islamic Azad University, Najafabad, Iran
| | - Hamid Nickho
- Department of Immunology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Shaghayegh Haghjooy Javanmard
- Applied Physiology Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Gordon A Ferns
- Brighton and Sussex Medical School, Division of Medical Education, Falmer, Brighton, Sussex, UK
| | - Mostafa Manian
- Department of Medical Laboratory Science, Faculty of Medical Science Kermanshah Branch, Islamic Azad University, Kermanshah, Iran.
- Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
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Blancas-Zugarazo SS, Langley E, Hidalgo-Miranda A. Exosomal lncRNAs as regulators of breast cancer chemoresistance and metastasis and their potential use as biomarkers. Front Oncol 2024; 14:1419808. [PMID: 39148900 PMCID: PMC11324554 DOI: 10.3389/fonc.2024.1419808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Accepted: 07/16/2024] [Indexed: 08/17/2024] Open
Abstract
Breast cancer is the most common cancer in women and the leading cause of female deaths by cancer in the world worldwide. Hence, understanding the molecular mechanisms associated with breast cancer development and progression, including drug resistance and breast cancer metastasis, is essential for achieving the best management of breast cancer patients. Cancer-related long noncoding RNAs have been shown to be involved in the regulation of each stage of breast cancer progression. Additionally, exosomes are extracellular microvesicles that are central to intercellular communication and play an important role in tumorigenesis. Exosomes can be released from primary tumor cells into the bloodstream and transmit cellular signals to distant body sites. In this work, we review the findings regarding the cellular mechanisms regulated by exosomal lncRNAs that are essentials to chemoresistance development and metastasis of breast cancer. Likewise, we evaluate the outcomes of the potential clinical use of exosomal lncRNAs as breast cancer biomarkers to achieve personalized management of the patients. This finding highlights the importance of transcriptomic analysis of exosomal lncRNAs to understand the breast cancer tumorigenesis as well as to improve the clinical tests available for this disease.
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Affiliation(s)
- Sugela Susana Blancas-Zugarazo
- Cátedras CONAHCYT (Consejo Nacional de Humanidades Ciencia y Tecnología) - Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico
| | - Elizabeth Langley
- Laboratorio de Cáncer Hormono Regulado, Instituto Nacional de Cancerología (INCAN), Mexico City, Mexico
| | - Alfredo Hidalgo-Miranda
- Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico
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10
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Yu J, Yu C, Jiang K, Yang G, Yang S, Tan S, Li T, Liang H, He Q, Wei F, Li Y, Cheng J, Wang F. Unveiling potential: urinary exosomal mRNAs as non-invasive biomarkers for early prostate cancer diagnosis. BMC Urol 2024; 24:163. [PMID: 39090720 PMCID: PMC11292860 DOI: 10.1186/s12894-024-01540-6] [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: 04/11/2024] [Accepted: 07/09/2024] [Indexed: 08/04/2024] Open
Abstract
BACKGROUND This study investigated the use of urinary exosomal mRNA as a potential biomarker for the early detection of prostate cancer (PCa). METHODS Next-generation sequencing was utilized to analyze exosomal RNA from 10 individuals with confirmed PCa and 10 individuals without cancer. Subsequent validation through qRT-PCR in a larger sample of 43 PCa patients and 92 healthy controls revealed distinct mRNA signatures associated with PCa. RESULTS Notably, mRNAs for RAB5B, WWP1, HIST2H2BF, ZFY, MARK2, PASK, RBM10, and NRSN2 showed promise as diagnostic markers, with AUC values between 0.799 and 0.906 and significance p values. Combining RAB5B and WWP1 in an exoRNA diagnostic model outperformed traditional PSA tests, achieving an AUC of 0.923, 81.4% sensitivity, and 89.1% specificity. CONCLUSIONS These findings highlight the potential of urinary exosomal mRNA profiling, particularly focusing on RAB5B and WWP1, as a valuable strategy for improving the early detection of PCa.
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Affiliation(s)
- Jiayin Yu
- Department of Urology, The First Affiliated Hospital of Guangxi Medical University, No.6 Shuangyong Road, Qingxiu, Nanning, Guangxi, 530021, P.R. China
| | - Chifei Yu
- Department of Urology, Affiliated Tumor Hospital of Guangxi Medical University, No.71 Hedi Road, Qingxiu District, Nanning, Guangxi, 530021, P.R. China
| | - Kangxian Jiang
- Department of Urology, The Second Affiliated Hospital of Fujian Medical University, No. 34 Zhongshan North Road, Quanzhou, Fujian, 362000, P.R. China
| | - Guanglin Yang
- Department of Urology, Affiliated Tumor Hospital of Guangxi Medical University, No.71 Hedi Road, Qingxiu District, Nanning, Guangxi, 530021, P.R. China
| | - Shubo Yang
- Department of Urology, The First Affiliated Hospital of Guangxi Medical University, No.6 Shuangyong Road, Qingxiu, Nanning, Guangxi, 530021, P.R. China
| | - Shuting Tan
- Department of Urology, The First Affiliated Hospital of Guangxi Medical University, No.6 Shuangyong Road, Qingxiu, Nanning, Guangxi, 530021, P.R. China
| | - Tingting Li
- Department of Urology, Affiliated Tumor Hospital of Guangxi Medical University, No.71 Hedi Road, Qingxiu District, Nanning, Guangxi, 530021, P.R. China
| | - Haiqi Liang
- Department of Urology, The First Affiliated Hospital of Guangxi Medical University, No.6 Shuangyong Road, Qingxiu, Nanning, Guangxi, 530021, P.R. China
| | - Qihuan He
- Department of Urology, The First Affiliated Hospital of Guangxi Medical University, No.6 Shuangyong Road, Qingxiu, Nanning, Guangxi, 530021, P.R. China
| | - Faye Wei
- Department of Urology, The First Affiliated Hospital of Guangxi Medical University, No.6 Shuangyong Road, Qingxiu, Nanning, Guangxi, 530021, P.R. China
| | - Yujian Li
- Department of Urology, The First Affiliated Hospital of Guangxi Medical University, No.6 Shuangyong Road, Qingxiu, Nanning, Guangxi, 530021, P.R. China
| | - Jiwen Cheng
- Department of Urology, The First Affiliated Hospital of Guangxi Medical University, No.6 Shuangyong Road, Qingxiu, Nanning, Guangxi, 530021, P.R. China.
- Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Medical University, No.22 Shuangyong Road, Qingxiu District, Nanning, Guangxi, 530021, P.R. China.
| | - Fubo Wang
- Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Medical University, No.22 Shuangyong Road, Qingxiu District, Nanning, Guangxi, 530021, P.R. China.
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11
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Pokorná M, Černá M, Boussios S, Ovsepian SV, O’Leary VB. lncRNA Biomarkers of Glioblastoma Multiforme. Biomedicines 2024; 12:932. [PMID: 38790894 PMCID: PMC11117901 DOI: 10.3390/biomedicines12050932] [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: 03/25/2024] [Revised: 04/15/2024] [Accepted: 04/18/2024] [Indexed: 05/26/2024] Open
Abstract
Long noncoding RNAs (lncRNAs) are RNA molecules of 200 nucleotides or more in length that are not translated into proteins. Their expression is tissue-specific, with the vast majority involved in the regulation of cellular processes and functions. Many human diseases, including cancer, have been shown to be associated with deregulated lncRNAs, rendering them potential therapeutic targets and biomarkers for differential diagnosis. The expression of lncRNAs in the nervous system varies in different cell types, implicated in mechanisms of neurons and glia, with effects on the development and functioning of the brain. Reports have also shown a link between changes in lncRNA molecules and the etiopathogenesis of brain neoplasia, including glioblastoma multiforme (GBM). GBM is an aggressive variant of brain cancer with an unfavourable prognosis and a median survival of 14-16 months. It is considered a brain-specific disease with the highly invasive malignant cells spreading throughout the neural tissue, impeding the complete resection, and leading to post-surgery recurrences, which are the prime cause of mortality. The early diagnosis of GBM could improve the treatment and extend survival, with the lncRNA profiling of biological fluids promising the detection of neoplastic changes at their initial stages and more effective therapeutic interventions. This review presents a systematic overview of GBM-associated deregulation of lncRNAs with a focus on lncRNA fingerprints in patients' blood.
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Affiliation(s)
- Markéta Pokorná
- Department of Medical Genetics, Third Faculty of Medicine, Charles University, Ruská 87, Vinohrady, 10000 Prague, Czech Republic; (M.Č.); (V.B.O.)
| | - Marie Černá
- Department of Medical Genetics, Third Faculty of Medicine, Charles University, Ruská 87, Vinohrady, 10000 Prague, Czech Republic; (M.Č.); (V.B.O.)
| | - Stergios Boussios
- Department of Medical Oncology, Medway NHS Foundation Trust, Gillingham ME7 5NY, UK;
- Faculty of Medicine, Health, and Social Care, Canterbury Christ Church University, Canterbury CT2 7PB, UK
- Faculty of Life Sciences & Medicine, School of Cancer & Pharmaceutical Sciences, King’s College London, Strand, London WC2R 2LS, UK
- Kent Medway Medical School, University of Kent, Canterbury CT2 7LX, UK
- AELIA Organization, 9th Km Thessaloniki-Thermi, 57001 Thessaloniki, Greece
| | - 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
| | - Valerie Bríd O’Leary
- Department of Medical Genetics, Third Faculty of Medicine, Charles University, Ruská 87, Vinohrady, 10000 Prague, Czech Republic; (M.Č.); (V.B.O.)
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12
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Sayyed AA, Vasudevan SS, Ahmad S, Sarker P, Prasad A, Khandelwalv S, Choudhary I, Kandrikar TY, Verma A, Ali SA, Gondaliya P, Arya N. Exosomal microRNA for diagnosis and prognosis of head and neck cancer. DIAGNOSTIC, PROGNOSTIC, AND THERAPEUTIC ROLE OF MICRORNAS IN HEAD AND NECK CANCER 2024:221-236. [DOI: 10.1016/b978-0-443-15968-8.00013-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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13
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Liu J, Hu X, Xin W, Wang X. Exosomal Non-coding RNAs: A New Approach to Melanoma Diagnosis and Therapeutic Strategy. Curr Med Chem 2024; 31:6084-6109. [PMID: 37877505 DOI: 10.2174/0109298673267553231017053329] [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: 06/15/2023] [Revised: 09/03/2023] [Accepted: 09/22/2023] [Indexed: 10/26/2023]
Abstract
Malignant melanoma (MM) is a highly aggressive cancer with a poor prognosis. Currently, although a variety of therapies are available for treating melanoma, MM is still a serious threat to the patient's life due to numerous factors, such as the recurrence of tumors, the emergence of drug resistance, and the lack of effective therapeutic agents. Exosomes are biologically active lipid-bilayer extracellular vesicles secreted by diverse cell types that mediate intercellular signal communication. Studies found that exosomes are involved in cancer by carrying multiple bioactive molecules, including non-- coding RNAs (ncRNAs). The ncRNAs have been reported to play an important role in regulating proliferation, angiogenesis, immune regulation, invasion, metastasis, and treatment resistance of tumors. However, the functional role of exosomal ncRNAs in MM remains unknown. Therefore, this review summarizes the current state of melanoma diagnosis, treatment, and the application of exosomal ncRNAs in MM patients, which may provide new insights into the mechanisms involved in melanoma progression and serve as biomarkers for diagnosis and therapeutic targets.
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Affiliation(s)
- Jie Liu
- Department of Dermatology, Skin Research Institute of Peking University Shenzhen Hospital, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong Province, China
| | - Xiaoping Hu
- Department of Dermatology, Skin Research Institute of Peking University Shenzhen Hospital, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong Province, China
| | - Wenqiang Xin
- Department of Neurology, University Medical Center Göttingen, Göttingen 37075, Germany
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China, 300052
| | - Xianbin Wang
- Department of Emergency Medicine, The Second Affiliated Hospital of Baotou Medical College, Baotou 014030, China
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14
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Minami S, Chikazu D, Ochiya T, Yoshioka Y. Extracellular vesicle-based liquid biopsies in cancer: Future biomarkers for oral cancer. Transl Oncol 2023; 38:101786. [PMID: 37713973 PMCID: PMC10509717 DOI: 10.1016/j.tranon.2023.101786] [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: 12/30/2022] [Revised: 09/01/2023] [Accepted: 09/08/2023] [Indexed: 09/17/2023] Open
Abstract
Oral cancer is the sixth most common cancer worldwide, with approximately 530,000 new cases and 300,000 deaths each year. The process of carcinogenesis is complex, and survival rates have not changed significantly in recent decades. Early detection of cancer, prognosis prediction, treatment selection, and monitoring of progression are important to improve survival. With the recent significant advances in analytical technology, liquid biopsy has made it possible to achieve these goals. In this review, we report new results from clinical and cancer research applications of liquid biopsy, focusing on extracellular vesicles (EVs) among the major targets of liquid biopsy, namely, circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and EVs. In addition, the potential application of EVs derived from gram-negative bacteria (outer membrane vesicles; OMVs) among oral bacteria, which have recently attracted much attention, to liquid biopsy for oral cancer will also be addressed.
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Affiliation(s)
- Sakura Minami
- Department of Molecular and Cellular Medicine, Institute of Medical Science, Tokyo Medical University, 6-7-1, Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan; Department of Oral and Maxillofacial Surgery, Tokyo Medical University, 6-7-1, Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan
| | - Daichi Chikazu
- Department of Oral and Maxillofacial Surgery, Tokyo Medical University, 6-7-1, Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan
| | - Takahiro Ochiya
- Department of Molecular and Cellular Medicine, Institute of Medical Science, Tokyo Medical University, 6-7-1, Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan
| | - Yusuke Yoshioka
- Department of Molecular and Cellular Medicine, Institute of Medical Science, Tokyo Medical University, 6-7-1, Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.
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15
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Bryja A, Zadka Ł, Farzaneh M, Zehtabi M, Ghasemian M, Dyszkiewicz-Konwińska M, Mozdziak P, Zabel M, Podhorska-Okołów M, Dzięgiel P, Piotrowska-Kempisty H, Kempisty B. Small extracellular vesicles - A host for advanced bioengineering and "Trojan Horse" of non-coding RNAs. Life Sci 2023; 332:122126. [PMID: 37769803 DOI: 10.1016/j.lfs.2023.122126] [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: 08/02/2023] [Revised: 09/19/2023] [Accepted: 09/25/2023] [Indexed: 10/03/2023]
Abstract
Small extracellular vesicles (sEVs) are a type of membranous vesicles that can be released by cells into the extracellular space. The relationship between sEVs and non-coding RNAs (ncRNAs) is highly intricate and interdependent. This symbiotic relationship plays a pivotal role in facilitating intercellular communication and holds profound implications for a myriad of biological processes. The concept of sEVs and their ncRNA cargo as a "Trojan Horse" highlights their remarkable capacity to traverse biological barriers and surreptitiously deliver their cargo to target cells, evading detection by the host-immune system. Accumulating evidence suggests that sEVs may be harnessed as carriers to ferry therapeutic ncRNAs capable of selectively silencing disease-driving genes, particularly in conditions such as cancer. This approach presents several advantages over conventional drug delivery methods, opening up new possibilities for targeted therapy and improved treatment outcomes. However, the utilization of sEVs and ncRNAs as therapeutic agents raises valid concerns regarding the possibility of unforeseen consequences and unintended impacts that may emerge from their application. It is important to consider the fundamental attributes of sEVs and ncRNAs, including by an in-depth analysis of the practical and clinical potentials of exosomes, serving as a representative model for sEVs encapsulating ncRNAs.
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Affiliation(s)
- Artur Bryja
- Division of Anatomy, Department of Human Morphology and Embryology, Wroclaw Medical University, Wrocław, Poland
| | - Łukasz Zadka
- Division of Ultrastructural Research, Wroclaw Medical University, Wrocław, Poland
| | - Maryam Farzaneh
- Fertility, Infertility and Perinatology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mojtaba Zehtabi
- Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Majid Ghasemian
- Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | | | - Paul Mozdziak
- Prestage Department of Poultry Science, North Carolina State University, Raleigh, USA
| | - Maciej Zabel
- Division of Ultrastructural Research, Wroclaw Medical University, Wrocław, Poland; Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, Wrocław, Poland; Division of Anatomy and Histology, University of Zielona Gora, Zielona Góra, Poland
| | | | - Piotr Dzięgiel
- Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, Wrocław, Poland
| | - Hanna Piotrowska-Kempisty
- Department of Toxicology, Poznan University of Medical Sciences, Poznań, Poland; Department of Basic and Preclinical Sciences, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, Poland
| | - Bartosz Kempisty
- Division of Anatomy, Department of Human Morphology and Embryology, Wroclaw Medical University, Wrocław, Poland; Prestage Department of Poultry Science, North Carolina State University, Raleigh, USA; Department of Obstetrics and Gynecology, University Hospital and Masaryk University, Brno, Czech Republic; Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, Toruń, Poland.
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16
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Wandrey M, Jablonska J, Stauber RH, Gül D. Exosomes in Cancer Progression and Therapy Resistance: Molecular Insights and Therapeutic Opportunities. Life (Basel) 2023; 13:2033. [PMID: 37895415 PMCID: PMC10608050 DOI: 10.3390/life13102033] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 10/04/2023] [Accepted: 10/05/2023] [Indexed: 10/29/2023] Open
Abstract
The development of therapy resistance still represents a major hurdle in treating cancers, leading to impaired treatment success and increased patient morbidity. The establishment of minimally invasive liquid biopsies is a promising approach to improving the early diagnosis, as well as therapy monitoring, of solid tumors. Because of their manifold functions in the tumor microenvironment, tumor-associated small extracellular vesicles, referred to as exosomes, have become a subject of intense research. Besides their important roles in cancer progression, metastasis, and the immune response, it has been proposed that exosomes also contribute to the acquisition and transfer of therapy resistance, mainly by delivering functional proteins and RNAs, as well as facilitating the export of active drugs or functioning as extracellular decoys. Extensive research has focused on understanding the molecular mechanisms underlying the occurrence of resistance and translating these into strategies for early detection. With this review, we want to provide an overview of the current knowledge about the (patho-)biology of exosomes, as well as state-of-the-art methods of isolation and analysis. Furthermore, we highlight the role of exosomes in tumorigenesis and cancer treatment, where they can function as therapeutic agents, biomarkers, and/or targets. By focusing on their roles in therapy resistance, we will reveal new paths of exploiting exosomes for cancer diagnosis and treatment.
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Affiliation(s)
- Madita Wandrey
- Nanobiomedicine/ENT Department, University Medical Center Mainz, Langenbeckstraße 1, 55131 Mainz, Germany; (M.W.); (R.H.S.)
| | - Jadwiga Jablonska
- Translational Oncology/ENT Department, University Hospital Essen, Hufelandstraße 55, 45147 Essen, Germany;
- German Cancer Consortium (DKTK) Partner Site Düsseldorf/Essen, 45147 Essen, Germany
| | - Roland H. Stauber
- Nanobiomedicine/ENT Department, University Medical Center Mainz, Langenbeckstraße 1, 55131 Mainz, Germany; (M.W.); (R.H.S.)
| | - Désirée Gül
- Nanobiomedicine/ENT Department, University Medical Center Mainz, Langenbeckstraße 1, 55131 Mainz, Germany; (M.W.); (R.H.S.)
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Masrour M, Khanmohammadi S, Fallahtafti P, Rezaei N. Long non-coding RNA as a potential diagnostic biomarker in head and neck squamous cell carcinoma: A systematic review and meta-analysis. PLoS One 2023; 18:e0291921. [PMID: 37733767 PMCID: PMC10513217 DOI: 10.1371/journal.pone.0291921] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Accepted: 09/09/2023] [Indexed: 09/23/2023] Open
Abstract
BACKGROUND Head and neck squamous cell carcinoma (HNSCC) is a group of malignancies arising from the epithelium of the head and neck. Despite efforts in treatment, results have remained unsatisfactory, and the death rate is high. Early diagnosis of HNSCC has clinical importance due to its high rates of invasion and metastasis. This systematic review and meta-analysis evaluated the diagnostic accuracy of lncRNAs in HNSCC patients. METHODS PubMed, ISI, SCOPUS, and EMBASE were searched for original publications published till April 2023 using MeSH terms and free keywords "long non-coding RNA" and "head and neck squamous cell carcinoma" and their expansions. The Reitsma bivariate random effect model pooled diagnostic test performance for studies that reported specificity and sensitivity; diagnostic AUC values from all trials were meta-analyzed using the random effects model with the inverse variance method. RESULTS The initial database search yielded 3209 articles, and 25 studies met our criteria. The cumulative sensitivity and specificity for lncRNAs in the diagnosis of HNSCC were 0.74 (95%CI: 0.68-0.7 (and 0.79 (95%CI: 0.74-0.83), respectively. The pooled AUC value for all specimen types was found to be 0.83. Using the inverse variance method, 71 individual lncRNAs yielded a pooled AUC of 0.77 (95%CI: 0.74-0.79). Five studies reported on the diagnostic accuracy of the MALAT1 lncRNA with a pooled AUC value of 0.83 (95%CI: 0.73-0.94). CONCLUSIONS LncRNAs could be used as diagnostic biomarkers for HNSCC, but further investigation is needed to validate clinical efficacy and elucidate mechanisms. High-throughput sequencing and bioinformatics should be used to ascertain expression profiles.
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Affiliation(s)
- Mahdi Masrour
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Shaghayegh Khanmohammadi
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | | | - Nima Rezaei
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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18
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Zhang H, Chen Z, Huang Q, Guo Y, Wang M, Wu C. Preliminary study using a small plasma extracellular vesicle miRNA panel as a potential biomarker for early diagnosis and prognosis in laryngeal cancer. Cell Oncol (Dordr) 2023; 46:1015-1030. [PMID: 36964893 DOI: 10.1007/s13402-023-00792-y] [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] [Accepted: 02/26/2023] [Indexed: 03/26/2023] Open
Abstract
PURPOSE Plasma extracellular vesicle (EV) miRNAs are important biomarkers for body fluid biopsy. The purpose of this study was to screen and construct a plasma small EV (sEV) miRNA panel as a biomarker for diagnosis and prognosis in laryngeal squamous cell carcinoma (LSCC). METHODS Plasma sEV miRNAs from 6 LSCC patients with three typical anatomical sites and 3 normal controls (NCs) were analyzed by next-generation sequencing. The aberrant expression profile of sEV miRNAs was compared with the online databases of LSCC to construct and verify the diagnostic and prognostic panel by machine learning. Additionally, quantitative real-time polymerase chain reaction (qRT‒PCR) was performed to validate the diagnostic efficacy of the screened miRNAs in an independent clinical cohort. RESULTS A plasma sEV miRNA panel (consisting of hsa-miR-139-3p, hsa-miR-486-5p, hsa-miR-944, hsa-miR-320b and hsa-miR-455-5p) was successfully constructed for the early diagnosis and prognosis of LSCC and showed good predictive potential with AUCs of 0.782, 1.000, 0.716, and 0.875 by an artificial neural network (ANN) panel in independent datasets. This panel was further validated in an independent cohort consisting of 84 clinical cases (48 LSCC and 36 NCs). In the validation cohort, the AUC of the 5 individual miRNAs ranged from 0.721 to 0.837. The accuracy was further increased by the logistic model, which further increased the AUC to 0.959 by adjusting for the number of miRNAs. The miRNA‒mRNA regulatory network and immune function analysis revealed the possible underlying pathogenesis of LSCC. CONCLUSION Plasma sEV miRNA panels can be promising plasma biomarkers for predicting early diagnosis and prognosis in LSCC.
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Affiliation(s)
- Haopeng Zhang
- Department of Otolaryngology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Zhengxun Chen
- Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Eye & ENT Hospital of Fudan University, 83 Fenyang Road, 200031, Shanghai, China
| | - Qiang Huang
- Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Eye & ENT Hospital of Fudan University, 83 Fenyang Road, 200031, Shanghai, China
| | - Yang Guo
- Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Eye & ENT Hospital of Fudan University, 83 Fenyang Road, 200031, Shanghai, China
| | - Mei Wang
- Department of Otolaryngology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
| | - Chunping Wu
- Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Eye & ENT Hospital of Fudan University, 83 Fenyang Road, 200031, Shanghai, China.
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Amicone L, Marchetti A, Cicchini C. The lncRNA HOTAIR: a pleiotropic regulator of epithelial cell plasticity. J Exp Clin Cancer Res 2023; 42:147. [PMID: 37308974 DOI: 10.1186/s13046-023-02725-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Accepted: 05/30/2023] [Indexed: 06/14/2023] Open
Abstract
The epithelial-to-mesenchymal transition (EMT) is a trans-differentiation process that endows epithelial cells with mesenchymal properties, including motility and invasion capacity; therefore, its aberrant reactivation in cancerous cells represents a critical step to gain a metastatic phenotype. The EMT is a dynamic program of cell plasticity; many partial EMT states can be, indeed, encountered and the full inverse mesenchymal-to-epithelial transition (MET) appears fundamental to colonize distant secondary sites. The EMT/MET dynamics is granted by a fine modulation of gene expression in response to intrinsic and extrinsic signals. In this complex scenario, long non-coding RNAs (lncRNAs) emerged as critical players. This review specifically focuses on the lncRNA HOTAIR, as a master regulator of epithelial cell plasticity and EMT in tumors. Molecular mechanisms controlling its expression in differentiated as well as trans-differentiated epithelial cells are highlighted here. Moreover, current knowledge about HOTAIR pleiotropic functions in regulation of both gene expression and protein activities are described. Furthermore, the relevance of the specific HOTAIR targeting and the current challenges of exploiting this lncRNA for therapeutic approaches to counteract the EMT are discussed.
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Affiliation(s)
- Laura Amicone
- Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Dipartimento di Medicina Molecolare, Sapienza University of Rome, Viale Regina Elena 324, Rome, 00161, Italy
| | - Alessandra Marchetti
- Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Dipartimento di Medicina Molecolare, Sapienza University of Rome, Viale Regina Elena 324, Rome, 00161, Italy
| | - Carla Cicchini
- Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Dipartimento di Medicina Molecolare, Sapienza University of Rome, Viale Regina Elena 324, Rome, 00161, Italy.
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20
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Logozzi M, Orefice NS, Di Raimo R, Mizzoni D, Fais S. The Importance of Detecting, Quantifying, and Characterizing Exosomes as a New Diagnostic/Prognostic Approach for Tumor Patients. Cancers (Basel) 2023; 15:cancers15112878. [PMID: 37296842 DOI: 10.3390/cancers15112878] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 05/11/2023] [Accepted: 05/22/2023] [Indexed: 06/12/2023] Open
Abstract
Exosomes are extracellular vesicles (EVs) of nanometric size studied for their role in tumor pathogenesis and progression and as a new source of tumor biomarkers. The clinical studies have provided encouraging but probably unexpected results, including the exosome plasmatic levels' clinical relevance and well-known biomarkers' overexpression on the circulating EVs. The technical approach to obtaining EVs includes methods to physically purify EVs and characterize EVs, such as Nanosight Tracking Analysis (NTA), immunocapture-based ELISA, and nano-scale flow cytometry. Based on the above approaches, some clinical investigations have been performed on patients with different tumors, providing exciting and promising results. Here we emphasize data showing that exosome plasmatic levels are consistently higher in tumor patients than in controls and that plasmatic exosomes express well-known tumor markers (e.g., PSA and CEA), proteins with enzymatic activity, and nucleic acids. However, we also know that tumor microenvironment acidity is a key factor in influencing both the amount and the characteristics of the exosome released by tumor cells. In fact, acidity significantly increases exosome release by tumor cells, which correlates with the number of exosomes that circulate through the body of a tumor patient.
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Affiliation(s)
- Mariantonia Logozzi
- Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy
| | - Nicola Salvatore Orefice
- Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
| | | | - Davide Mizzoni
- ExoLab Italia, Tecnopolo d'Abruzzo, 67100 L'Aquila, Italy
| | - Stefano Fais
- Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy
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21
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Gong XY, Chen HB, Lu ZY, Zhu C, Chen DS, Chen X. Prospective role of liquid biopsy for early screening in laryngeal cancer. Invest New Drugs 2023:10.1007/s10637-023-01365-4. [PMID: 37129839 DOI: 10.1007/s10637-023-01365-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 04/20/2023] [Indexed: 05/03/2023]
Affiliation(s)
- Xiao-Yang Gong
- Department of Otorhinolaryngology, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, China
| | - Hai-Bing Chen
- Department of Otorhinolaryngology, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, China
| | - Zhao-Yi Lu
- Department of Otorhinolaryngology, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, China
| | - Chan Zhu
- Department of Otorhinolaryngology, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, China
| | - Dong-Sheng Chen
- The State Key Lab of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd, Nanjing, 210002, China
| | - Xi Chen
- Department of Otorhinolaryngology, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, China.
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22
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Horozoglu C, Bal G, Kabadayı B, Hakan MT, Sönmez D, Nacarkahya G, Verim A, Yaylım İ. lncRNA NORAD, soluble ICAM1 and their correlations may be related to the regulation of the tumor immune microenvironment in laryngeal squamous cell carcinoma (LSCC). Pathol Res Pract 2023; 246:154494. [PMID: 37172522 DOI: 10.1016/j.prp.2023.154494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 03/28/2023] [Accepted: 04/28/2023] [Indexed: 05/15/2023]
Abstract
NORAD, non-coding RNA activated by DNA damage, is a Long non-coding RNA (lncRNA) transcript that modulates genome stability and has been reported to be dysregulated in different cancers. Although it has been reported to be upregulated in tumor cells mostly for solid organ cancers, it has also been reported to be downregulated in some cancers. Although the pathophysiological mechanism is not fully understood, a negative correlation between NORAD and intercellular cell adhesion molecule-1 (ICAM-1) has been shown in experimental models, but this situation has not been evaluated in terms of cancer. We aimed to evaluate the potential roles of these two biomarker candidates together and separately in the clinicopathological axis in Laryngeal squamous cell carcinoma (LSCC) in a case-control study setting. The interactions of NORAD and ICAM1 at the RNA level were evaluated interactively by the RIblast program. sICAM1 (soluble intercellular cell adhesion molecule-1) levels were determined by ELISA in one hundred and five individuals (forty-four LSCC, sixty-one control) and lncRNA NORAD expression in eighty-eight tissues (forty-four LSCC tumors, forty-four tumor-free surrounding tissues) was determined by Real-time PCR. While the energy treesholud was - 16 kcal/mol between NORAD and ICAM1, the total energy was 176.33 kcal/mol, and 9 base pair pairings from 4 critical points were detected. NORAD expression level was found to be higher in tumor surrounding tissue compared to tumor tissue, and sICAM1 was higher in the control group compared to LSCC (p = 0.004; p = 0.02). NORAD discreminte tumor surrounding tissue from tumor (AUC: 0.674; optimal sensitivity:87.50%; optimal specificity 54.55%; cut-off point as >1.58 fold change; P = 0.034). The sICAM1 level was found to be higher in the control (494,814 ± 93.64 ng/L) than LSCC (432.95 ± 93.64 ng/L) (p = 0.02). sICAM1 discreminte control group from LSCC (AUC: 0.624; optimal sensitivity 68,85%; optimal specificity 61,36%; cut-off point ≤115,0 ng/L; (p = 0.033). A very strong negative correlation was found between NORAD expression and patients' sICAM1 levels (r = -.967; n = 44; p = 0.033). sICAM1 levels were found to be 1.63 times higher in NORAD downregulated subjects compared to upregulated ones (p = 0.031). NORAD was 3.63 times higher in those with alcohol use, and sICAM 1 was 5.77 times higher in those without distant organ metastasis (p = 0.043; 0.004). The increased NORAD expression in the tumor microenvironment in LSCC, the activation of T cells via TCR signaling, and the decrease of sICAM in the control group in correlation with NORAD suggests that ICAM1 may be needed as a membrane protein in the tumor microenvironment. NORAD and ICAM1 may be functionally related to tumor microenvironment and immune control in LSCC.
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Affiliation(s)
- Cem Horozoglu
- Faculty of Medicine, Halic University, Istanbul, Turkey
| | - Görkem Bal
- Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | | | - Mehmet Tolgahan Hakan
- Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
| | - Dilara Sönmez
- Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
| | - Gulper Nacarkahya
- Department of Medical Biology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
| | - Aysegul Verim
- Department of Otorhinolaryngology/Head and Neck Surgery, Haydarpasa Numune Education and Research Hospital, Istanbul, Turkey
| | - İlhan Yaylım
- Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
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23
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Ni Q, Zhang H, Shi X, Li X. Exosomal lncRNA HCG18 contributes to cholangiocarcinoma growth and metastasis through mediating miR-424-5p/SOX9 axis through PI3K/AKT pathway. Cancer Gene Ther 2023; 30:582-595. [PMID: 36854894 PMCID: PMC10104778 DOI: 10.1038/s41417-022-00500-2] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 05/04/2022] [Accepted: 06/23/2022] [Indexed: 03/02/2023]
Abstract
Cholangiocarcinoma is a highly aggressive malignant tumor disease with the increasing incidence and mortality. It's urgent to identify specific biomarkers for cholangiocarcinoma treatment and diagnosis. Recent studies have noted the importance of lncRNAs in cancer and the following downstream mechanism with miRNAs network has been a hotspot. This work aimed to discover the role of lncRNA HCG18 and its possible downstream mechanism in cholangiocarcinoma tumor progression. Initially, through bioinformatics tools, we observed abnormal expression of lncRNA HCG18 in cholangiocarcinoma. In vitro experiments like (CCK-8, EdU, colony formation, flow cytometry, transwell, wound healing assays) and animal study confirmed that lncRNA HCG18 served as a cancer-promoting gene, promoted cancer proliferation, migration and invasion abilities. Besides, we found cancer cell-secreted exosomes transitted HCG18 to surrounding tumor cells and accelerated tumor growth and metastasis. After that, we confirmed HCG18 directly interacted with miR-424-5p through FISH, RIP and dual luciferase reporter assays with negative modulation. The inhibition of miR-424-5p reversed the HCG18 knockdown induced suppression on cholangiocarcinoma cancer cells. More specific, miR-424-5p targeted to SOX9 contributed to cholangiocarcinoma growth and metastasis through mediating PI3K/AKT pathway. In conclusion, these findings provide solid evidence of lncRNAs/miRNAs regulation in cholangiocarcinoma progression.
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Affiliation(s)
- Qingfeng Ni
- The First Affiliated Hospital of Nanjing Medical University, The National Institute of Living Donor Liver Transplantation, Nanjing, Jiangsu, 210029, P. R. China
| | - Hai Zhang
- The First Affiliated Hospital of Nanjing Medical University, The National Institute of Living Donor Liver Transplantation, Nanjing, Jiangsu, 210029, P. R. China
| | - Xiaoli Shi
- The First Affiliated Hospital of Nanjing Medical University, The National Institute of Living Donor Liver Transplantation, Nanjing, Jiangsu, 210029, P. R. China
| | - Xiangcheng Li
- The First Affiliated Hospital of Nanjing Medical University, The National Institute of Living Donor Liver Transplantation, Nanjing, Jiangsu, 210029, P. R. China.
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24
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Extracellular Vesicles as Biomarkers in Head and Neck Squamous Cell Carcinoma: From Diagnosis to Disease-Free Survival. Cancers (Basel) 2023; 15:cancers15061826. [PMID: 36980712 PMCID: PMC10046514 DOI: 10.3390/cancers15061826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 03/14/2023] [Accepted: 03/15/2023] [Indexed: 03/22/2023] Open
Abstract
Head and neck squamous cell carcinomas (HNSCCs) arising from different anatomical sites present with different incidences and characteristics, which requires a personalized treatment strategy. Despite the extensive research that has conducted on this malignancy, HNSCC still has a poor overall survival rate. Many attempts have been made to improve the outcomes, but one of the bottlenecks is thought to be the lack of an effective biomarker with high sensitivity and specificity. Extracellular vesicles (EVs) are secreted by various cells and participate in a great number of intercellular communications. Based on liquid biopsy, EV detection in several biofluids, such as blood, saliva, and urine, has been applied to identify the existence and progression of a variety of cancers. In HNSCC, tumor-derived EVs exhibit many functionalities by transporting diverse cargoes, which highlights their importance in tumor screening, the determination of multidisciplinary therapy, prediction of prognosis, and evaluation of therapeutic effects. This review illustrates the classification and formation of EV subtypes, the cargoes conveyed by these vesicles, and their respective functions in HNSCC cancer biology, and discloses their potential as biomarkers during the whole process of tumor diagnosis, treatment, and follow-up.
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25
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Head and neck cancer biomarkers: Systematic review and meta-analysis. Clin Chim Acta 2023; 542:117280. [PMID: 36878379 DOI: 10.1016/j.cca.2023.117280] [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: 01/20/2023] [Revised: 03/01/2023] [Accepted: 03/01/2023] [Indexed: 03/07/2023]
Abstract
PURPOSE To perform a systematic review and meta-analysis of the diagnostic capabilities of various biological markers in the plasma, serum, tissue, and saliva of patients with head and neck cancer (HNC). METHODS We performed manual and digital searches using specific keywords and found English-language literature published up to October 28, 2022. PubMed, ScienceDirect, Scopus, MEDLINE Complete, and EMBASE databases were used. Studies comparing biomarkers for the diagnosis of HNC versus healthy controls were evaluated. RESULTS Seventeen studies using varied sources of biomarkers, both individually and combined, were identified. The sensitivity and specificity of biomarkers ranged from 29.5% to 100% and 57.1% to 100%, respectively. The combined biomarkers demonstrated higher therapeutic applicability in terms of sensitivity and specificity than the individual biomarkers. Furthermore, the heterogeneity of the sensitivity/specificity for individual and combined biomarker was 534.45/1.66 and 247.41/14.62, respectively. CONCLUSION Combined biomarkers may aid in the diagnosis of HNC. Further studies are required to verify the accuracy of these biomarkers.
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26
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Armakolas A, Kotsari M, Koskinas J. Liquid Biopsies, Novel Approaches and Future Directions. Cancers (Basel) 2023; 15:1579. [PMID: 36900369 PMCID: PMC10000663 DOI: 10.3390/cancers15051579] [Citation(s) in RCA: 42] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Revised: 02/22/2023] [Accepted: 03/01/2023] [Indexed: 03/06/2023] Open
Abstract
Cancer is among the leading causes of death worldwide. Early diagnosis and prognosis are vital to improve patients' outcomes. The gold standard of tumor characterization leading to tumor diagnosis and prognosis is tissue biopsy. Amongst the constraints of tissue biopsy collection is the sampling frequency and the incomplete representation of the entire tumor bulk. Liquid biopsy approaches, including the analysis of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating miRNAs, and tumor-derived extracellular vesicles (EVs), as well as certain protein signatures that are released in the circulation from primary tumors and their metastatic sites, present a promising and more potent candidate for patient diagnosis and follow up monitoring. The minimally invasive nature of liquid biopsies, allowing frequent collection, can be used in the monitoring of therapy response in real time, allowing the development of novel approaches in the therapeutic management of cancer patients. In this review we will describe recent advances in the field of liquid biopsy markers focusing on their advantages and disadvantages.
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Affiliation(s)
- Athanasios Armakolas
- Physiology Laboratory, Medical School, National and Kapodistrian University of Athens, 115 27 Athens, Greece
- B' Department of Medicine, Hippokration Hospital, National and Kapodistrian University of Athens, 115 27 Athens, Greece
| | - Maria Kotsari
- Physiology Laboratory, Medical School, National and Kapodistrian University of Athens, 115 27 Athens, Greece
| | - John Koskinas
- B' Department of Medicine, Hippokration Hospital, National and Kapodistrian University of Athens, 115 27 Athens, Greece
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27
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Galindo Torres BP, García Girón C, Alcaraz Ortega R, Saiz López P, Adiego Leza MI, Grijalba Uche MV. Knowledge and expectations about miRNAs as biomarkers in head and neck squamous cell cancers. Am J Otolaryngol 2023; 44:103771. [PMID: 36603378 DOI: 10.1016/j.amjoto.2022.103771] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 12/18/2022] [Indexed: 12/31/2022]
Abstract
Head and neck squamous cell cancer patients suffer from a high postoperative recurrence rate and poor prognosis. Thus, it is essential to better understand the underlying molecular mechanisms and identify the role of new biomarkers. Recent research has shown that the dysregulation of microRNAs is a potential biomarker as a screening or prognostic tool. Moreover, the literature reveals its promising usefulness to select the best treatment strategy and monitor tumour response. The purpose of this review is to identify and synthesize the available literature on microRNAs as biomarkers that could help manage patients with head and neck squamous cell cancer. A search in scientific databases was completed, including all relevant articles related to circulating microRNAs in head and neck squamous cell cancer published in English or Spanish. We focused on articles whose main findings were related to their usefulness in diagnosis and prognosis. Conclusion: Knowledge of microRNAs opens the possibilities that these molecules offer in terms of monitoring cancer disease in a less-invasive, simple manner, allowing for serial sampling to assess the response to treatment and minimal residual disease. It is yet to be determined whether liquid biopsy will replace the traditional biopsy in the future but it represents a change in the paradigm of management of head and neck squamous cell cancer.
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Affiliation(s)
| | | | | | - Patricia Saiz López
- Pathological Anatomy Department, Universitary Hospital of Burgos, Burgos, Spain
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28
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Bueno-Urquiza LJ, Martínez-Barajas MG, Villegas-Mercado CE, García-Bernal JR, Pereira-Suárez AL, Aguilar-Medina M, Bermúdez M. The Two Faces of Immune-Related lncRNAs in Head and Neck Squamous Cell Carcinoma. Cells 2023; 12:cells12050727. [PMID: 36899863 PMCID: PMC10000590 DOI: 10.3390/cells12050727] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 01/15/2023] [Accepted: 01/21/2023] [Indexed: 03/02/2023] Open
Abstract
Head and neck squamous cell carcinoma (HNSCC) is a group of cancers originating from the mucosal epithelium in the oral cavity, larynx, oropharynx, nasopharynx, and hypopharynx. Molecular factors can be key in the diagnosis, prognosis, and treatment of HNSCC patients. Long non-coding RNAs (lncRNAs) are molecular regulators composed of 200 to 100,000 nucleotides that act on the modulation of genes that activate signaling pathways associated with oncogenic processes such as proliferation, migration, invasion, and metastasis in tumor cells. However, up until now, few studies have discussed the participation of lncRNAs in modeling the tumor microenvironment (TME) to generate a protumor or antitumor environment. Nevertheless, some immune-related lncRNAs have clinical relevance, since AL139158.2, AL031985.3, AC104794.2, AC099343.3, AL357519.1, SBDSP1, AS1AC108010.1, and TM4SF19-AS1 have been associated with overall survival (OS). MANCR is also related to poor OS and disease-specific survival. MiR31HG, TM4SF19-AS1, and LINC01123 are associated with poor prognosis. Meanwhile, LINC02195 and TRG-AS1 overexpression is associated with favorable prognosis. Moreover, ANRIL lncRNA induces resistance to cisplatin by inhibiting apoptosis. A superior understanding of the molecular mechanisms of lncRNAs that modify the characteristics of TME could contribute to increasing the efficacy of immunotherapy.
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Affiliation(s)
- Lesly J. Bueno-Urquiza
- Department of Physiology, University Center for Health Sciences, University of Guadalajara, Guadalajara 44340, Mexico
| | - Marcela G. Martínez-Barajas
- Department of Physiology, University Center for Health Sciences, University of Guadalajara, Guadalajara 44340, Mexico
| | | | - Jonathan R. García-Bernal
- Department of Physiology, University Center for Health Sciences, University of Guadalajara, Guadalajara 44340, Mexico
| | - Ana L. Pereira-Suárez
- Department of Microbiology and Pathology, University Center for Health Sciences, University of Guadalajara, Guadalajara 44340, Mexico
| | - Maribel Aguilar-Medina
- Faculty of Biological and Chemical Sciences, Autonomous University of Sinaloa, Culiacán, Sinaloa 80030, Mexico
| | - Mercedes Bermúdez
- Faculty of Dentistry, Autonomous University of Chihuahua, Chihuahua 31000, Mexico
- Correspondence: ; Tel.: +52-(614)-439-1834
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29
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Huang Z, Yang X, Huang Y, Tang Z, Chen Y, Liu H, Huang M, Qing L, Li L, Wang Q, Jie Z, Jin X, Jia B. Saliva - a new opportunity for fluid biopsy. Clin Chem Lab Med 2023; 61:4-32. [PMID: 36285724 DOI: 10.1515/cclm-2022-0793] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Accepted: 09/29/2022] [Indexed: 12/15/2022]
Abstract
Saliva is a complex biological fluid with a variety of biomolecules, such as DNA, RNA, proteins, metabolites and microbiota, which can be used for the screening and diagnosis of many diseases. In addition, saliva has the characteristics of simple collection, non-invasive and convenient storage, which gives it the potential to replace blood as a new main body of fluid biopsy, and it is an excellent biological diagnostic fluid. This review integrates recent studies and summarizes the research contents of salivaomics and the research progress of saliva in early diagnosis of oral and systemic diseases. This review aims to explore the value and prospect of saliva diagnosis in clinical application.
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Affiliation(s)
- Zhijie Huang
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Xiaoxia Yang
- Department of Endodontics, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Yisheng Huang
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Zhengming Tang
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Yuanxin Chen
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Hongyu Liu
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Mingshu Huang
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Ling Qing
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Li Li
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Qin Wang
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Zhuye Jie
- BGI Genomics, BGI-Shenzhen, Shenzhen, P.R. China
- Shenzhen Key Laboratory of Human Commensal Microorganisms and Health Research, BGI-Shenzhen, Shenzhen, P.R. China
- Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark
| | - Xin Jin
- BGI Genomics, BGI-Shenzhen, Shenzhen, P.R. China
- School of Medicine, South China University of Technology, Guangzhou, P.R. China
| | - Bo Jia
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
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30
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Broseghini E, Filippini DM, Fabbri L, Leonardi R, Abeshi A, Dal Molin D, Fermi M, Ferracin M, Fernandez IJ. Diagnostic and Prognostic Value of microRNAs in Patients with Laryngeal Cancer: A Systematic Review. Noncoding RNA 2023; 9:ncrna9010009. [PMID: 36827542 PMCID: PMC9966707 DOI: 10.3390/ncrna9010009] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 01/16/2023] [Accepted: 01/17/2023] [Indexed: 01/20/2023] Open
Abstract
Laryngeal squamous cell cancer (LSCC) is one of the most common malignant tumors of the head and neck region, with a poor survival rate (5-year overall survival 50-80%) as a consequence of an advanced-stage diagnosis and high recurrence rate. Tobacco smoking and alcohol abuse are the main risk factors of LSCC development. An early diagnosis of LSCC, a prompt detection of recurrence and a more precise monitoring of the efficacy of different treatment modalities are currently needed to reduce the mortality. Therefore, the identification of effective diagnostic and prognostic biomarkers for LSCC is crucial to guide disease management and improve clinical outcomes. In the past years, a dysregulated expression of small non-coding RNAs, including microRNAs (miRNAs), has been reported in many human cancers, including LSCC, and many miRNAs have been explored for their diagnostic and prognostic potential and proposed as biomarkers. We searched electronic databases for original papers that were focused on miRNAs and LSCC, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. According to the outcome, 566 articles were initially screened, of which 177 studies were selected and included in the analysis. In this systematic review, we provide an overview of the current literature on the function and the potential diagnostic and prognostic role of tissue and circulating miRNAs in LSCC.
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Affiliation(s)
- Elisabetta Broseghini
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, Università di Bologna, 40138 Bologna, Italy
- Correspondence: (E.B.); (D.M.F.)
| | - Daria Maria Filippini
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, Università di Bologna, 40138 Bologna, Italy
- Division of Medical Oncology, IRCCS Azienda Ospedaliero, Universitaria Policlinico Sant’Orsola Malpighi of Bologna, 40138 Bologna, Italy
- Correspondence: (E.B.); (D.M.F.)
| | - Laura Fabbri
- Division of Medical Oncology, IRCCS Azienda Ospedaliero, Universitaria Policlinico Sant’Orsola Malpighi of Bologna, 40138 Bologna, Italy
| | - Roberta Leonardi
- Division of Medical Oncology, IRCCS Azienda Ospedaliero, Universitaria Policlinico Sant’Orsola Malpighi of Bologna, 40138 Bologna, Italy
| | - Andi Abeshi
- Department of Otorhinolaryngology—Head and Neck Surgery, IRCCS Azienda Ospedaliero, Universitaria di Bologna, Policlinico S. Orsola-Malpighi, 40138 Bologna, Italy
| | - Davide Dal Molin
- Department of Otorhinolaryngology—Head and Neck Surgery, IRCCS Azienda Ospedaliero, Universitaria di Bologna, Policlinico S. Orsola-Malpighi, 40138 Bologna, Italy
| | - Matteo Fermi
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, Università di Bologna, 40138 Bologna, Italy
- Department of Otorhinolaryngology—Head and Neck Surgery, IRCCS Azienda Ospedaliero, Universitaria di Bologna, Policlinico S. Orsola-Malpighi, 40138 Bologna, Italy
| | - Manuela Ferracin
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, Università di Bologna, 40138 Bologna, Italy
- IRCCS Azienda Ospedaliero, Universitaria di Bologna, 40138 Bologna, Italy
| | - Ignacio Javier Fernandez
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, Università di Bologna, 40138 Bologna, Italy
- Department of Otorhinolaryngology—Head and Neck Surgery, IRCCS Azienda Ospedaliero, Universitaria di Bologna, Policlinico S. Orsola-Malpighi, 40138 Bologna, Italy
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31
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Xiang Y, Hua Q. The Role and Mechanism of Long Non-Coding RNA HOTAIR in the Oncogenesis, Diagnosis, and Treatment of Head and Neck Squamous Cell Carcinoma. Clin Med Insights Oncol 2023; 17:11795549231169099. [PMID: 37153904 PMCID: PMC10161338 DOI: 10.1177/11795549231169099] [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: 10/20/2022] [Accepted: 03/26/2023] [Indexed: 05/10/2023] Open
Abstract
The most frequent malignant tumor of the head and neck is head and neck squamous cell carcinoma (HNSCC), which has a high frequency, a poor prognosis in the late stages, and subpar therapeutic results. As a result, early HNSCC diagnosis and treatment are urgently needed; however, there are no good diagnostic biomarkers or efficient therapeutic targets at this time. The long-stranded non-coding RNA HOTAIR may be important in the pathogenesis of cancer, according to recent research. By interactions with DNA, RNA, and proteins, it has been demonstrated that HOTAIR, a >200 nucleotide RNA transcript, plays a role in the biological processes of many types of tumor cells, including proliferation, metastasis, and prognosis of HNSCC. Hence, this review discusses HOTAIR's function and molecular mechanisms in HNSCC.
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Affiliation(s)
| | - Qingquan Hua
- Qingquan Hua, Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, People’s Republic of China.
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Abstract
Exosomes are extracellular vesicles, which have the ability to convey various types of cargo between cells. Lately, a great amount of interest has been paid to exosomal microRNAs (miRNAs), since much evidence has suggested that the sorting of miRNAs into exosomes is not an accidental process. It has been shown that exosomal miRNAs (exo-miRNAs) are implicated in a variety of cellular processes including (but not limited to) cell migration, apoptosis, proliferation, and autophagy. Exosomes can play a role in cardiovascular diseases and can be used as diagnostic biomarkers for several diseases, especially cancer. Tremendous advances in technology have led to the development of various platforms for miRNA profiling. Each platform has its own limitations and strengths that need to be understood in order to use them properly. In the current review, we summarize some exo-miRNAs that are relevant to exo-miRNA profiling studies and describe new methods used for the measurement of miRNA profiles in different human bodily fluids.
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Wang J, Wang N, Zheng Z, Che Y, Suzuki M, Kano S, Lu J, Wang P, Sun Y, Homma A. Exosomal lncRNA HOTAIR induce macrophages to M2 polarization via PI3K/ p-AKT /AKT pathway and promote EMT and metastasis in laryngeal squamous cell carcinoma. BMC Cancer 2022; 22:1208. [PMID: 36424539 PMCID: PMC9686105 DOI: 10.1186/s12885-022-10210-5] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2022] [Accepted: 10/21/2022] [Indexed: 11/25/2022] Open
Abstract
Exosomes are a new way of the communication between the tumor cell and macrophage in the micro-environment. The macrophage can be induced to different phenotypes according to the different tumors. In the present study, long-chain noncoding RNA HOTAIR (lncRNA HOTAIR) was highly expressed in LSCC and exosomes. The pathway of exosomal lncRNA HOTAIR inducing macrophage to M2 polarization in the LSCC was investigated. The carcinoma tissues and adjacent tissues were collected from 104 LSCC cases, and the positive relationship between CD163-/CD206-M2 macrophage infiltration and clinical phase, lymph node spreading and pathological phase in LSCC was observed. To examine the role of exosomal lncRNA HOTAIR, macrophages were co-cultured with LSCC-exosomes of high lncRNA HOTAIR expression or transferred with HOTAIR mimics. It was suggested that exosomal lncRNA HOTAIR can induce macrophages to M2 polarization by PI3K/p-AKT/AKT signaling pathway. Furthermore, exo-treated M2 macrophages facilitate the migration, proliferation, and EMT of LSCC.
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Affiliation(s)
- Jingting Wang
- grid.412463.60000 0004 1762 6325Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Nan Wang
- grid.412463.60000 0004 1762 6325Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Zeyu Zheng
- grid.412463.60000 0004 1762 6325Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Yanlu Che
- grid.412463.60000 0004 1762 6325Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Masanobu Suzuki
- grid.39158.360000 0001 2173 7691Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Satoshi Kano
- grid.39158.360000 0001 2173 7691Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Jianguang Lu
- grid.412463.60000 0004 1762 6325Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Peng Wang
- grid.412463.60000 0004 1762 6325Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Yanan Sun
- grid.412463.60000 0004 1762 6325Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Akihiro Homma
- grid.39158.360000 0001 2173 7691Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan
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The Exosomal miR-1246 of Laryngeal Squamous Cell Carcinoma Induces Polarization of M2 Type Macrophages and Promotes the Invasiveness of Laryngeal Squamous Cell Carcinoma. JOURNAL OF ONCOLOGY 2022; 2022:4424221. [PMID: 36199785 PMCID: PMC9529393 DOI: 10.1155/2022/4424221] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 08/18/2022] [Accepted: 09/02/2022] [Indexed: 11/18/2022]
Abstract
Background. The possible role and detailed mechanisms of Tumor-associated macrophages (TAMs) in laryngeal squamous cell carcinoma (LSCC) have not been revealed. Methods. The expressions of typical markers were evaluated by qRT-PCR. In macrophages cocultured with TU212 cells, CD163, and CD206 protein expressions were detected by western blot analysis; IL-10 and IL-12 expressions were detected by ELISA assay. Exosomes isolated from TU212 cells were characterized by TEM analysis. As for the TU212 cells cocultured with macrophages processed with HOK or TU212 cells derived exosomes, their viability, migration, and invasion were assessed by CCK-8 assay, wounding healing, and Transwell assays, respectively. Results. In this study, macrophages processed with exosomes from human TU212 cells notably advanced LSCC cell viability, migration, and invasion. miR-1246 inhibitor suppressed the M2 polarization of macrophages. Macrophages transfected with miR-1246 inhibitor suppressed LSCC cell viability, migration, and invasion. Conclusion. In summary, our data implied that the exosomal, miR-1246 of LSCC, induced polarization of M2 type macrophages and promoted the progression of LSCC. This trial is registered with 2020-13.
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Yigider AP, Yigit O. Biomarkers in Otorhinolaryngology. Biomark Med 2022. [DOI: 10.2174/9789815040463122010013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Biomarkers of otorhinolaryngologic diseases with higher insult over a
person’s him/herself and overall health services are summarized in brief. In order to
define, diagnose, treat and monitor any disease markers are needed.
Otorhinolaryngology (ORL) is interested in special disease entities of the region
besides otorhinolaryngologic involvements of the systemic diseases and unique forms
of pathologies such as cholesteatoma, Meniere’s disease and otosclerosis. Neoplasia is
another heading to deal with. In the following chapter, one will find an overview of
molecules that have been used as a biomarker as well as the end points of the present
research on the issue relevant with ORL. Day by day, new molecules are being named
however, the pathways of action are rather the same. Readers will find the headings
related to the most common diseases of the field, informing them about where to look
for defining new strategies of understanding of each disease.
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Affiliation(s)
- Ayse Pelin Yigider
- Istanbul Research and Training Hospital Otorhinolaryngology,Istanbul Research and Training Hospital Otorhinolaryngology, Istanbul,Turkey
| | - Ozgur Yigit
- Istanbul Research and Training Hospital Otorhinolaryngology, Istanbul, Turkey
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Bano A, Vats R, Yadav P, Bhardwaj R. Exosomics in oral cancer diagnosis, prognosis, and therapeutics - An emergent and imperative non-invasive natural nanoparticle-based approach. Crit Rev Oncol Hematol 2022; 178:103799. [PMID: 36031170 DOI: 10.1016/j.critrevonc.2022.103799] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 08/02/2022] [Accepted: 08/23/2022] [Indexed: 10/15/2022] Open
Abstract
Exosomes- the natural nanoparticles belonging to heterogeneous vesicles are released via nearly all sorts of cells, including tumour cells, to oprate intercellular communication. Selective packaging of exosomes amid nucleic acids, phospholipids, and proteins makes them ideal for intercellular communications occurring among different cells. The existence of exosomes has been validated in various biofluids, including saliva. Being non-invasive and in direct contact with oral malignant cells, saliva establishes itself as a preeminent source of early cancer biomarkers. In context, the role and providence of both recipient and donor secreting cells are persuaded through exosomal cargo.Several studies have emphasized the influence of exosomal contents in different stages of cancer development, reconciling interactions between tumour cells and their surrounding niche. More explicitly, a transformation of exosomal contents such as nucleic acids, lipids, and proteins can endorse tumour progression and help ascertain a secluded pre-metastatic niche crammed with substances that errand cancer cell proliferation,angiogenesis, metastasis, and drug resistance. The blooming field of exosomes has directed the evolution of high-end isolation and characterization techniques along with the development of an entirely new field- exosomics that comprises complete analysis of exosomal cargo in various physiological conditions, including oral cancer. Researchers have discovered multiple pathways involved in exosome biogenesis to understand numerous events associated with cancer progression. Tissue-specific packaging of exosomes makes them a novel source of prognostic and diagnostic biomarkers and potential therapeutic targets. The extent of the current review confers the contemporary perception of the versatile task of exosomes, especially salivary exosomes, as potential biomarkers in the progression and diagnosis as well as therapeutics of oral cancers and their potential employment in clinical applications.
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Affiliation(s)
- Afsareen Bano
- Centre for Medical Biotechnology, Maharshi Dayanand University, Rohtak, Haryana, India.
| | - Ravina Vats
- Centre for Medical Biotechnology, Maharshi Dayanand University, Rohtak, Haryana, India.
| | - Pooja Yadav
- Centre for Medical Biotechnology, Maharshi Dayanand University, Rohtak, Haryana, India.
| | - Rashmi Bhardwaj
- Centre for Medical Biotechnology, Maharshi Dayanand University, Rohtak, Haryana, India.
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Thomaidou AC, Batsaki P, Adamaki M, Goulielmaki M, Baxevanis CN, Zoumpourlis V, Fortis SP. Promising Biomarkers in Head and Neck Cancer: The Most Clinically Important miRNAs. Int J Mol Sci 2022; 23:ijms23158257. [PMID: 35897831 PMCID: PMC9367895 DOI: 10.3390/ijms23158257] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 07/18/2022] [Accepted: 07/21/2022] [Indexed: 02/01/2023] Open
Abstract
Head and neck cancers (HNCs) comprise a heterogeneous group of tumors that extend from the oral cavity to the upper gastrointestinal tract. The principal etiologic factors for oral tumors include tobacco smoking and alcohol consumption, while human papillomavirus (HPV) infections have been accused of a high incidence of pharyngeal tumors. Accordingly, HPV detection has been extensively used to categorize carcinomas of the head and neck. The diverse nature of HNC highlights the necessity for novel, sensitive, and precise biomarkers for the prompt diagnosis of the disease, its successful monitoring, and the timely prognosis of patient clinical outcomes. In this context, the identification of certain microRNAs (miRNAs) and/or the detection of alterations in their expression patterns, in a variety of somatic fluids and tissues, could serve as valuable biomarkers for precision oncology. In the present review, we summarize some of the most frequently studied miRNAs (including miR-21, -375, -99, -34a, -200, -31, -125a/b, -196a/b, -9, -181a, -155, -146a, -23a, -16, -29, and let-7), their role as biomarkers, and their implication in HNC pathogenesis. Moreover, we designate the potential of given miRNAs and miRNA signatures as novel diagnostic and prognostic tools for successful patient stratification. Finally, we discuss the currently ongoing clinical trials that aim to identify the diagnostic, prognostic, or therapeutic utility of miRNAs in HNC.
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Affiliation(s)
- Arsinoe C. Thomaidou
- Biomedical Applications Unit, Institute of Chemical Biology, National Hellenic Research Foundation (NHRF), 11635 Athens, Greece; (A.C.T.); (M.A.)
| | - Panagiota Batsaki
- Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, 11522 Athens, Greece; (P.B.); (M.G.); (C.N.B.)
| | - Maria Adamaki
- Biomedical Applications Unit, Institute of Chemical Biology, National Hellenic Research Foundation (NHRF), 11635 Athens, Greece; (A.C.T.); (M.A.)
| | - Maria Goulielmaki
- Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, 11522 Athens, Greece; (P.B.); (M.G.); (C.N.B.)
| | - Constantin N. Baxevanis
- Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, 11522 Athens, Greece; (P.B.); (M.G.); (C.N.B.)
| | - Vassilis Zoumpourlis
- Biomedical Applications Unit, Institute of Chemical Biology, National Hellenic Research Foundation (NHRF), 11635 Athens, Greece; (A.C.T.); (M.A.)
- Correspondence: (V.Z.); (S.P.F.); Tel.: +30-210-727-3730 (V.Z.); +30-210-640-9462 (S.P.F.)
| | - Sotirios P. Fortis
- Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, 11522 Athens, Greece; (P.B.); (M.G.); (C.N.B.)
- Correspondence: (V.Z.); (S.P.F.); Tel.: +30-210-727-3730 (V.Z.); +30-210-640-9462 (S.P.F.)
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Liquid Biopsy in Head and Neck Cancer: Current Evidence and Future Perspective on Squamous Cell, Salivary Gland, Paranasal Sinus and Nasopharyngeal Cancers. Cancers (Basel) 2022; 14:cancers14122858. [PMID: 35740523 PMCID: PMC9221064 DOI: 10.3390/cancers14122858] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Accepted: 06/06/2022] [Indexed: 01/27/2023] Open
Abstract
Simple Summary Head and neck cancer is the sixth most common type of solid tumor and harbors a poor prognosis since most patients are diagnosed at an advanced stage. The study of different tumor components in the blood, saliva or other body fluids is called liquid biopsy. The introduction of novel diagnostic tools such as liquid biopsy could aid in achieving earlier diagnoses and more accurate disease monitoring during treatment. In this manuscript, the reader will find an in-depth review of the current evidence and a future perspective on the role of liquid biopsy in head and neck cancer. Abstract Head and neck cancer (HNC) is currently the sixth most common solid malignancy, accounting for a 50% five-year mortality rate. In the past decade, substantial improvements in understanding its molecular biology have allowed for a growing development of new biomarkers. Among these, the field of liquid biopsy has seen a sustained growth in HNC, demonstrating the feasibility to detect different liquid biomarkers such as circulating tumor DNA (ctDNA), circulating tumor cells (CTC), extracellular vesicles and microRNAs. Liquid biopsy has been studied in HPV-negative squamous cell carcinoma of the head and neck (SCCHN) but also in other subentities such as HPV-related SCCHN, EBV-positive nasopharyngeal cancer and oncogene-driven salivary gland cancers. However, future studies should be internally and externally validated, and ideally, clinical trials should incorporate the use of liquid biomarkers as endpoints in order to prospectively demonstrate their role in HNC. A thorough review of the current evidence on liquid biopsy in HNC as well as its prospects will be conducted.
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Li Y, Gao S, Hu Q, Wu F. Functional Properties of Cancer Epithelium and Stroma-Derived Exosomes in Head and Neck Squamous Cell Carcinoma. Life (Basel) 2022; 12:life12050757. [PMID: 35629423 PMCID: PMC9145061 DOI: 10.3390/life12050757] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Accepted: 05/13/2022] [Indexed: 12/24/2022] Open
Abstract
Stroma–cancer cell crosstalk involves a complex signaling network that contributes to tumor progression, including carcinogenesis, angiogenesis, migration, invasion, and therapy resistance in cancers. Exosomes, as extracellular membranous nanovesicles released by almost all types of cells, including tumor cells and stromal cells, play a critical role in signal delivery and material communication, in which the characteristics of their parent cells are reflected. The tumor or stroma-derived exosomes mediate cell–cell communication in the tumor microenvironment by transporting DNA, RNA, proteins, lipids, and metabolites. Recent studies on head and neck squamous cell carcinoma (HNSCC) have demonstrated that tumor-derived exosomes support various tumor biological behaviors, whereas the functional roles of stroma-derived exosomes remain largely unknown. Although these exosomes are emerging as promising targets in early diagnosis, prognostic prediction, and pharmaceutical carriers for antitumor therapy, there are still multiple hurdles to be overcome before they can be used in clinical applications. Herein, we systematically summarize the promotive roles of the epithelium and stroma-derived exosomes in HNSCC and highlight the potential clinical applications of exosomes in the treatment of HNSCC.
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Affiliation(s)
- Yang Li
- Department of Oral Pathology, College of Stomatology, Ningxia Medical University, South Sheng Li Street 804, Yinchuan 750004, China;
- Key Laboratory of Stomatology of Fujian Province, School and Hospital of Stomatology, Fujian Medical University, Yang Qiao Middle Road 246, Fuzhou 350004, China
| | - Shengtao Gao
- State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, South Renmin Road, Sec. 3, No. 14, Chengdu 610041, China;
| | - Qi Hu
- College of Public Health and Management, Ningxia Medical University, South Sheng Li Street 1160, Yinchuan 750004, China;
| | - Fanglong Wu
- State Key Laboratory of Oral Diseases, National Center of Stomatology, National Clinical Research Center for Oral Diseases, Frontier Innovation Center for Dental Medicine Plus, West China Hospital of Stomatology, Sichuan University, South Renmin Road, Sec. 3, No. 14, Chengdu 610041, China
- Correspondence:
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Shuang Y, Yao X, Liu J, Niu J, Guo W, Li C. Serum-derived extracellular vesicles mediate Smad4 expression through shuttling microRNA-27a in the progression of laryngeal squamous cell carcinoma. Hum Cell 2022; 35:1084-1099. [PMID: 35545731 DOI: 10.1007/s13577-022-00712-6] [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: 11/02/2021] [Accepted: 04/25/2022] [Indexed: 11/04/2022]
Abstract
Serum-derived extracellular vesicles (EVs) containing non-coding RNAs have been indicated to serve as diagnostic and prognostic biomarkers for laryngeal squamous cell carcinoma (LSCC), while their functional role remains to be explored. Here, we summarize the possible mechanism explaining the laryngeal carcinogenesis and the associated changes with the involvement of extracellular microRNA (miR)-27a from serum of LSCC patients. Serum-derived EVs from LSCC patients were found to increase the proliferative activity and decreased the apoptotic activity of LSCC cells. miRNA microarrays revealed that miR-27a expression was elevated after EV treatment. miR-27a expression was elevated in LSCC tissues and predicted a poor prognosis for patients. Downregulation of miR-27a inhibited the effect of EVs to reduce the activity of LSCC cells in vitro and to suppress tumor development in vivo. miR-27a targeted SMAD family member 4 (Smad4) to mediate the Wnt/β-catenin pathway, which was induced under the influence of EVs. Smad4 was downregulated in LSCC tissues, and simultaneous overexpression of miR-27a and Smad4 resulted in reduced cell activity and tumorigenicity. In conclusion, serum-derived EVs support the laryngeal carcinogenesis at least partially via transferring miR-27a. miR-27a targets Smad4 and is a biomarker to predict LSCC prognosis.
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Affiliation(s)
- Yu Shuang
- Department of Otorhinolaryngology Head and Neck Surgery, The Second Hospital of Tianjin Medical University, No. 23, Pingjiang Road, Tianjin, 300211, People's Republic of China.
| | - Xiaofeng Yao
- Department of Maxillofacial and Otorhinolaryngology Head and Neck Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjing, 300202, People's Republic of China
| | - Jing Liu
- Department of Otorhinolaryngology Head and Neck Surgery, The Second Hospital of Tianjin Medical University, No. 23, Pingjiang Road, Tianjin, 300211, People's Republic of China
| | - Juntao Niu
- Department of Otorhinolaryngology Head and Neck Surgery, The Second Hospital of Tianjin Medical University, No. 23, Pingjiang Road, Tianjin, 300211, People's Republic of China
| | - Wenyu Guo
- Department of Otorhinolaryngology Head and Neck Surgery, The Second Hospital of Tianjin Medical University, No. 23, Pingjiang Road, Tianjin, 300211, People's Republic of China
| | - Chao Li
- Department of Otorhinolaryngology Head and Neck Surgery, The Second Hospital of Tianjin Medical University, No. 23, Pingjiang Road, Tianjin, 300211, People's Republic of China
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Iacob R, Mandea M, Iacob S, Pietrosanu C, Paul D, Hainarosie R, Gheorghe C. Liquid Biopsy in Squamous Cell Carcinoma of the Esophagus and of the Head and Neck. Front Med (Lausanne) 2022; 9:827297. [PMID: 35572996 PMCID: PMC9098838 DOI: 10.3389/fmed.2022.827297] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Accepted: 02/15/2022] [Indexed: 11/13/2022] Open
Abstract
Squamous cell carcinomas of the esophagus (ESCC) and of the head and neck (HNSCC) are two neoplasms that share common risk factors and have the same embryological origin, but a very different prognosis, the 5-year survival of HNSCC being almost double (40–50%) compared to the 5-year survival of ESCC (20%). Current guidelines emphasize the importance of screening for ESCC in patients diagnosed with head and neck cancers. A liquid biopsy is a novel tool for diagnosis, prognostic stratification, and personalized therapy. Liquid biopsy biomarkers for these two malignancies could help both their early detection, facilitate residual disease identification, and provide prognosis information. The present systematic review of the literature was aimed at describing the liquid biopsy biomarkers present in these two malignancies, with an emphasis on potential clinical applications.
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Affiliation(s)
- Razvan Iacob
- University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Matei Mandea
- University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
| | - Speranta Iacob
- University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Catalina Pietrosanu
- University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
- Professor Doctor Dorin Hociota Institute of Phonoaudiology and Functional ENT Surgery, Bucharest, Romania
| | - Doru Paul
- Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, United States
| | - Razvan Hainarosie
- University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
- Professor Doctor Dorin Hociota Institute of Phonoaudiology and Functional ENT Surgery, Bucharest, Romania
- *Correspondence: Razvan Hainarosie
| | - Cristian Gheorghe
- University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
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Falco M, Tammaro C, Takeuchi T, Cossu AM, Scafuro G, Zappavigna S, Itro A, Addeo R, Scrima M, Lombardi A, Ricciardiello F, Irace C, Caraglia M, Misso G. Overview on Molecular Biomarkers for Laryngeal Cancer: Looking for New Answers to an Old Problem. Cancers (Basel) 2022; 14:1716. [PMID: 35406495 PMCID: PMC8997012 DOI: 10.3390/cancers14071716] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 03/01/2022] [Accepted: 03/24/2022] [Indexed: 11/19/2022] Open
Abstract
Laryngeal squamous cell cancer (LSCC) accounts for almost 25-30% of all head and neck squamous cell cancers and is clustered according to the affected districts, as this determines distinct tendency to recur and metastasize. A major role for numerous genetic alterations in driving the onset and progression of this neoplasm is emerging. However, major efforts are still required for the identification of molecular markers useful for both early diagnosis and prognostic definition of LSCC that is still characterized by significant morbidity and mortality. Non-coding RNAs appear the most promising as they circulate in all the biological fluids allowing liquid biopsy determination, as well as due to their quick and characteristic modulation useful for non-invasive detection and monitoring of cancer. Other critical aspects are related to recent progress in circulating tumor cells and DNA detection, in metastatic status and chemo-refractoriness prediction, and in the functional interaction of LSCC with chronic inflammation and innate immunity. We review all these aspects taking into account the progress of the technologies in the field of next generation sequencing.
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Affiliation(s)
- Michela Falco
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.F.); (C.T.); (T.T.); (A.M.C.); (G.S.); (S.Z.); (A.L.); (M.C.)
| | - Chiara Tammaro
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.F.); (C.T.); (T.T.); (A.M.C.); (G.S.); (S.Z.); (A.L.); (M.C.)
| | - Takashi Takeuchi
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.F.); (C.T.); (T.T.); (A.M.C.); (G.S.); (S.Z.); (A.L.); (M.C.)
- Molecular Diagnostics Division, Wakunaga Pharmaceutical Co., Ltd., Hiroshima 739-1195, Japan
| | - Alessia Maria Cossu
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.F.); (C.T.); (T.T.); (A.M.C.); (G.S.); (S.Z.); (A.L.); (M.C.)
- Laboratory of Molecular and Precision Oncology, Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy;
| | - Giuseppe Scafuro
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.F.); (C.T.); (T.T.); (A.M.C.); (G.S.); (S.Z.); (A.L.); (M.C.)
| | - Silvia Zappavigna
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.F.); (C.T.); (T.T.); (A.M.C.); (G.S.); (S.Z.); (A.L.); (M.C.)
| | - Annalisa Itro
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy;
| | - Raffaele Addeo
- Oncology Operative Unit, Hospital of Frattamaggiore, ASLNA-2NORD, 80020 Naples, Italy;
| | - Marianna Scrima
- Laboratory of Molecular and Precision Oncology, Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy;
| | - Angela Lombardi
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.F.); (C.T.); (T.T.); (A.M.C.); (G.S.); (S.Z.); (A.L.); (M.C.)
| | | | - Carlo Irace
- Department of Pharmacy, School of Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, Italy;
| | - Michele Caraglia
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.F.); (C.T.); (T.T.); (A.M.C.); (G.S.); (S.Z.); (A.L.); (M.C.)
- Laboratory of Molecular and Precision Oncology, Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy;
| | - Gabriella Misso
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.F.); (C.T.); (T.T.); (A.M.C.); (G.S.); (S.Z.); (A.L.); (M.C.)
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LncRNA Biomarkers of Inflammation and Cancer. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2022; 1363:121-145. [PMID: 35220568 DOI: 10.1007/978-3-030-92034-0_7] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
Long noncoding RNAs (lncRNAs) are promising candidates as biomarkers of inflammation and cancer. LncRNAs have several properties that make them well-suited as molecular markers of disease: (1) many lncRNAs are expressed in a tissue-specific manner, (2) distinct lncRNAs are upregulated based on different inflammatory or oncogenic stimuli, (3) lncRNAs released from cells are packaged and protected in extracellular vesicles, and (4) circulating lncRNAs in the blood are detectable using various RNA sequencing approaches. Here we focus on the potential for lncRNA biomarkers to detect inflammation and cancer, highlighting key biological, technological, and analytical considerations that will help advance the development of lncRNA-based liquid biopsies.
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More than a Bubble: Extracellular Vesicle microRNAs in Head and Neck Squamous Cell Carcinoma. Cancers (Basel) 2022; 14:cancers14051160. [PMID: 35267467 PMCID: PMC8909139 DOI: 10.3390/cancers14051160] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2022] [Revised: 02/18/2022] [Accepted: 02/22/2022] [Indexed: 12/11/2022] Open
Abstract
Simple Summary Head and neck squamous cell carcinoma (HNSCC) is an aggressive and lethal disease. Despite diagnostic and therapeutic advances, the overall survival of patients with advanced HNSCC remains poor. Recently, microRNAs in extracellular vesicles (EV-miRNAs) have been proposed as essential regulatory molecules involved in HNSCC. EV-miRNAs may serve as disease biomarkers and represent a novel therapeutic target. This review summarizes the current understanding of the role of EV-miRNAs in HNSCC as well as their potential future clinical applications. Abstract MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that play a pivotal regulatory role in a broad variety of biological processes. Dysregulation of miRNAs is associated with several human diseases, particularly cancer. Extracellular vesicles (EVs) are crucial components in intercellular communication. As part of the cargo of EVs, miRNAs are involved in EV-mediated cell-to-cell interactions, including promotion or suppression of tumor development. The knowledge on the molecular mechanisms and clinical importance of EV-miRNAs in head and neck squamous cell carcinoma (HNSCC) has rapidly grown over the past years. In the present review, the current understanding regarding the effect of EV-miRNAs on HNSCC tumorigenesis is summarized, which includes effects on tumor proliferation, angiogenesis, invasion and metastasis, the tumor microenvironment, immune modulation, and treatment resistance. EV-miRNA-based biomarkers in liquid biopsies such as blood and saliva may open up new possibilities for employing EV-miRNAs for screening and early diagnostics as well as disease monitoring. Future perspectives include the promise of EV-miRNAs as a novel therapeutic target.
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Cappello F, Fais S. Extracellular vesicles in cancer pros and cons: the importance of the evidence-based medicine. Semin Cancer Biol 2022; 86:4-12. [DOI: 10.1016/j.semcancer.2022.01.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 01/18/2022] [Accepted: 01/28/2022] [Indexed: 12/17/2022]
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Bigagli E, Locatello LG, Di Stadio A, Maggiore G, Valdarnini F, Bambi F, Gallo O, Luceri C. Extracellular vesicles miR-210 as a potential biomarker for diagnosis and survival prediction of oral squamous cell carcinoma patients. J Oral Pathol Med 2021; 51:350-357. [PMID: 34800057 PMCID: PMC9300091 DOI: 10.1111/jop.13263] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 10/06/2021] [Accepted: 11/17/2021] [Indexed: 12/14/2022]
Abstract
Background The identification of early diagnostic and prognostic biomarkers in oral squamous cell carcinoma (OSCC) is an unmet clinical need. We hypothesized that extracellular vesicles miR‐210 expression (EV‐miR‐210) could be a potential biomarker for OSCC diagnosis and follow‐up. Methods The expression of EV‐miR‐210 was measured in the plasma of OSCC patients (n = 30) and compared to that of controls (n = 14). Results The median EV‐miR‐210 expression was significantly higher in OSCC patients compared to controls who had often, undetectable levels (p < 0.0001). We performed receiver operating characteristic (ROC) analysis for discriminating OSCC cases from controls. EV‐miR‐210 yielded an area under the curve (AUC) of 0.9513 with sensitivity 92.3% and specificity 86.6%. Kaplan‐Meier curves indicated that high EV‐miR‐210 expression was associated with worse 3 years’ survival (p < 0.05). Cox regression hazard model indicated that high EV‐miR‐210, G2, and G3 grading and pathological nodal status (pN)>1 were independent predictors of worse survival in OSCC patients. Conclusion These preliminary data suggest that EV‐mir‐210 may be a novel diagnostic and prognostic biomarker in OSCC.
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Affiliation(s)
- Elisabetta Bigagli
- Department of Neuroscience, Psychology, Drug Research and Child Health - NEUROFARBA - Section, University of Florence, Florence, Italy
| | | | - Arianna Di Stadio
- Department of Otolaryngology, Silvestrini University Hospital, University of Perugia, Perugia, Italy
| | | | - Francesca Valdarnini
- Department of Neuroscience, Psychology, Drug Research and Child Health - NEUROFARBA - Section, University of Florence, Florence, Italy
| | - Franco Bambi
- Cell Factory Meyer, "A. Meyer" University Children's Hospital, Florence, Italy
| | - Oreste Gallo
- Department of Otorhinolaryngology, Careggi University Hospital, Florence, Italy
| | - Cristina Luceri
- Department of Neuroscience, Psychology, Drug Research and Child Health - NEUROFARBA - Section, University of Florence, Florence, Italy
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Wu C, Wang M, Huang Q, Guo Y, Gong H, Hu C, Zhou L. Aberrant expression profiles and bioinformatic analysis of CAF-derived exosomal miRNAs from three moderately differentiated supraglottic LSCC patients. J Clin Lab Anal 2021; 36:e24108. [PMID: 34788477 PMCID: PMC8761437 DOI: 10.1002/jcla.24108] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2021] [Revised: 07/18/2021] [Accepted: 10/28/2021] [Indexed: 12/16/2022] Open
Abstract
Background Aberrant expression of exosomal miRNAs has emerged as a research hotspot. However, no studies have been conducted on the dysregulation of exosomal miRNAs derived from cancer‐associated fibroblasts (CAFs) in supraglottic laryngeal squamous cell carcinoma (SLSCC). Methods Cancer‐associated fibroblasts and paired normal fibroblasts (NFs) from SLSCC patients were cultured, and exosomes in the culture supernatants were collected and identified. Exosomal miRNA expression was compared in each pair of CAFs and NFs by next‐generation sequencing, and expression of selected exosomal miRNAs was validated by reverse transcription‑quantitative PCR. Four online bioinformatic algorithms predicted the potential target genes of aberrantly expressed miRNAs, while gene ontology and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment and network analysis identified downstream target genes and their interactions. Results Three pairs of CAFs and NFs were successfully cultured and purified. CAF‐derived exosomal miRNAs were mostly downregulated and included miR‐656‐3p, miR‐337‐5p, miR‐29a‐3p and miR‐655‐3p; however, some, including miR‐184‐3p, miR‐92a‐1‐5p, miR‐212‐3p and miR‐3135b, were upregulated. Bioinformatics analysis revealed involvement of these miRNAs in biological processes, cellular components and molecular functions. KEGG analysis revealed the top 30 pathways involvement in cancer initiation and progression and in cell cycle regulation. An interaction network showed miR‐16‐5p, miR‐29a‐3p, miR‐34c‐5p, miR‐32‐5p and miR‐490‐5p as the top five miRNAs and CCND1, CDKN1B, CDK6, PTEN and FOS as the top five target genes. Conclusions SLSCC patients showed aberrant expression of CAF‐derived exosomal miRNAs. The top five miRNAs and their target genes may jointly constitute a carcinogenic tumour microenvironment and act as biomarkers for SLSCC intervention.
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Affiliation(s)
- Chunping Wu
- Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Eye & ENT Hospital of Fudan University, Shanghai, China
| | - Mei Wang
- Department of Otolaryngology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Qiang Huang
- Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Eye & ENT Hospital of Fudan University, Shanghai, China
| | - Yang Guo
- Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Eye & ENT Hospital of Fudan University, Shanghai, China
| | - Hongli Gong
- Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Eye & ENT Hospital of Fudan University, Shanghai, China
| | - Chunyan Hu
- Department of Pathology, Eye & ENT Hospital of Fudan University, Shanghai, China
| | - Liang Zhou
- Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Eye & ENT Hospital of Fudan University, Shanghai, China
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MicroRNAs: Their Role in Metabolism, Tumor Microenvironment, and Therapeutic Implications in Head and Neck Squamous Cell Carcinoma. Cancers (Basel) 2021; 13:cancers13225604. [PMID: 34830755 PMCID: PMC8615702 DOI: 10.3390/cancers13225604] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 10/30/2021] [Accepted: 11/05/2021] [Indexed: 02/07/2023] Open
Abstract
Simple Summary Head and neck squamous cell carcinoma (HNSCC), which arises from the oral epithelium, is one of the most common cancers worldwide. Despite excellent diagnosis and treatment improvements, the mortality rate associated with HNSCC is still extremely high. Current data suggest that dysregulation of exosomes and metabolic abnormalities are involved in the initiation and progression of HNSCC. Thus, approaches for targeting exosomes in the tumor microenvironment and metabolic reprogramming pathways represent potential therapeutic strategies. Moreover, some miRNAs are thought to have significant functions in regulating the progression of HNSCC. The present article aims to summarize the current knowledge concerning the important miRNAs in both exosomes and cancer metabolism, as well as discuss future perspectives regarding their future diagnostic potential and treatment recommendations. Abstract MicroRNAs (miRNAs) are endogenous small non-coding RNA molecules that negatively regulate gene expression by binding to target mRNAs. Deregulated miRNAs can act as either oncogenic miRNAs or tumor suppressor miRNAs in controlling proliferation, differentiation, apoptosis, metastasis, epithelial–mesenchymal transition, and immune responses, which are all involved in the carcinogenesis process of HNSCC. Recent findings have shown that metabolic reprogramming is an important hallmark of cancer, which is necessary for malignant transformation and tumor development. Some reprogrammed metabolisms are believed to be required for HNSCC against an unfavorable tumor microenvironment (TME). The TME is composed of various cell types embedded in the altered extracellular matrix, among which exosomes, secreted by cancer cells, are one of the most important factors. Tumor-derived exosomes reshape the tumor microenvironment and play a crucial role in cell-to-cell communication during HNSCC development. Exosomes encapsulate many biomolecules, including miRNAs, circulate in body fluids, and can transmit intercellular regulatory messages to nearby and distant sites, which indicates that exosomal miRNAs have the potential to become non-invasive biomarkers. This review aims to clarify the functions of diverse miRNAs in HNSCC metabolic reprogramming and tumor-derived exosomes. In addition, it also emphasizes the potential role of miRNA as a biomarker in the diagnosis, prognosis, and treatment of HNSCC cancer.
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Liu SY, Liao Y, Hosseinifard H, Imani S, Wen QL. Diagnostic Role of Extracellular Vesicles in Cancer: A Comprehensive Systematic Review and Meta-Analysis. Front Cell Dev Biol 2021; 9:705791. [PMID: 34722499 PMCID: PMC8555429 DOI: 10.3389/fcell.2021.705791] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 09/13/2021] [Indexed: 12/12/2022] Open
Abstract
Background: Cancer-derived extracellular vesicles (EVs) are regarded to have significant function in most steps during cancer progression. This meta-analysis aims to investigate the accuracy of EVs as a biomarker in cancer diagnosis. Methods: The diagnostic efficacy of EVs for different cancers was assessed using pooled sensitivity and specificity, diagnostic odds ratio (DOR), and overall area under the curve (AUC) of the summary receiver operating characteristic (SROC). The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were verified to estimate the diagnostic efficacy of EV at a clinical level. Results: In all, 6,183 cancer patients and 2,437 healthy controls from 75 eligible studies reported in 42 publications were included in the study. The overall pooled sensitivity, specificity, PLR, NLR, and DOR were 0.62 (95% CI: 0.60–0.63), 0.76 (95% CI: 0.75–0.78), 3.07 (95% CI: 2.52–3.75), 0.34 (95% CI: 0.28–0.41), and 10.98 (95% CI: 7.53–16.00), respectively. Similarly, the AUC of the SROC was 0.88, indicating a high conservation of EVs as an early diagnostic marker. Furthermore, subgroup analysis suggested that the use of small EVs as a biomarker was more accurate in serum-based samples of nervous system cancer (p < 0.001). As a result, ultracentrifugation and quantification and size determination methods, such as Western blotting and ELISA were the most reliable identification methods for EV detection. We also indicated that increased secretion of EVs made them a capable biomarker for diagnosing cancer in elderly European individuals. Conclusions: Our study provides evidence that EVs are a promising non-invasive biomarker for cancer diagnosis. Well-designed cohort studies should be conducted to warrant the clinical diagnostic value of EVs.
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Affiliation(s)
- Shu-Ya Liu
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.,Department of Oncology, Chengdu Jinniu District People's Hospital, Chengdu, China
| | - Yin Liao
- Department of Oncology, People's Hospital of Renshou, Meishan, China
| | - Hossein Hosseinifard
- Research Center for Evidence Based Medicine (RCEBM), Tabriz University of Medical Sciences, Tabriz, Iran
| | - Saber Imani
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Qing-Lian Wen
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
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Nie H, Liao Z, Wang Y, Zhou J, He X, Ou C. Exosomal long non-coding RNAs: Emerging players in cancer metastasis and potential diagnostic biomarkers for personalized oncology. Genes Dis 2021; 8:769-780. [PMID: 34522707 PMCID: PMC8427254 DOI: 10.1016/j.gendis.2020.12.004] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 12/06/2020] [Accepted: 12/12/2020] [Indexed: 02/07/2023] Open
Abstract
Metastasis is a major challenge in the treatment of cancer. Exosomes are a class of small extracellular vesicles (EVs) that play critical roles in several human diseases, especially cancer, by transferring information (e.g., DNA, RNA, and protein) via cell-to-cell communication. Numerous recent studies have shown that exosomal long non-coding RNAs (lncRNAs) play crucial regulatory roles in cancer metastasis in the tumor microenvironment by altering the expression of several key signaling pathways and molecules. Due to their specificity and sensitivity, exosomal lncRNAs have potential as novel tumor markers and therapeutic targets in the treatment of cancer metastasis. In this review, we aim to summarize the roles of exosomal lncRNAs in cancer metastasis, the mechanisms underlying their roles, and their potential clinical applications.
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Affiliation(s)
- Hui Nie
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, PR China
| | - Zhujun Liao
- Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, PR China
| | - Yutong Wang
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, PR China
| | - Jianhua Zhou
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, PR China
| | - Xiaoyun He
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, PR China
| | - Chunlin Ou
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, PR China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, PR China
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