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Hu CC, Wang SG, Gao Z, Qing MF, Pan S, Liu YY, Li F. Emerging salivary biomarkers for early detection of oral squamous cell carcinoma. World J Clin Oncol 2025; 16:103803. [DOI: 10.5306/wjco.v16.i4.103803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2024] [Revised: 01/23/2025] [Accepted: 03/06/2025] [Indexed: 03/26/2025] Open
Abstract
Oral cancer, particularly oral squamous cell carcinoma (OSCC), remains a leading cause of cancer-related morbidity and mortality, with delayed diagnosis being a major contributing factor. Although salivary biomarkers have been explored for over three decades, the need for reliable, non-invasive diagnostic methods that enable early detection and continuous monitoring of OSCC remains unmet. This review aims to provide an updated overview of the latest advancements in salivary biomarker research, focusing on emerging biomarkers such as interleukin-6, interleukin-8, microRNAs and DNA methylation patterns, as well as metabolites and microbiota, all of which show significant promise for early OSCC detection. In addition to discussing well-established biomarkers, we explore recent technological developments that increase the sensitivity and specificity of these biomarkers, such as mass spectrometry, multiplex assays, and nanobiosensors. These developments are complemented by the integration of artificial intelligence for data analysis, which enables more accurate, point-of-care diagnostics that could revolutionize oral cancer screening. This review not only consolidates current knowledge but also addresses the challenges that hinder the widespread clinical adoption of salivary diagnostics, such as saliva variability and assay standardization. By overcoming these barriers, salivary biomarker-based diagnostics have the potential to transform OSCC detection, offering a non-invasive, cost-effective solution that can improve early diagnosis and patient outcomes.
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Affiliation(s)
- Cheng-Chen Hu
- Department of Stomatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Sheng-Guo Wang
- Department of Stomatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Zhi Gao
- Department of Stomatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Mao-Feng Qing
- Department of Stomatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Shan Pan
- Department of Stomatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Ying-Ying Liu
- Department of Stomatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Fang Li
- Department of General Surgery, Chongqing General Hospital, Chongqing 401147, China
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Rashid S, Puttagunta P, Pamulapati S, Yang J, Pocha S, Saba NF, Teng Y. Leveraging Saliva for Insights into Head and Neck Cancer. Int J Mol Sci 2024; 25:13514. [PMID: 39769275 PMCID: PMC11678725 DOI: 10.3390/ijms252413514] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Revised: 12/13/2024] [Accepted: 12/14/2024] [Indexed: 01/11/2025] Open
Abstract
Head and neck cancer (HNC) represents a heterogeneous group of malignancies with increasing global incidence and notable mortality. Early detection is essential for improving survival rates and minimizing recurrence; however, existing diagnostic methods are often invasive and complex. There is a need for noninvasive and more effective approaches for early detection and real-time monitoring of HNC. Saliva contains various biomolecules that may serve as indicators of HNC. As a result, saliva-based biomarkers have emerged as a transformative approach in the diagnosis and treatment of HNC due to their ease of collection, non-invasiveness, and potential to provide details about biomolecular changes associated with cancer progression. This narrative review synthesizes the current literature on the potential of saliva as a noninvasive diagnostic tool for HNC. It highlights various biomarkers found in saliva, including cell-free DNA, RNA, proteins, and metabolites, and explores emerging technologies in saliva detection that could transform the future of HNC management. Continued research efforts and larger-scale validation studies are essential to fully realize the potential of saliva-based biopsy and help pinpoint notable biomarkers to improve patient outcomes and reduce mortality associated with HNC worldwide.
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Affiliation(s)
- Saad Rashid
- Internal Medicine Program, Mercyhealth Graduate Medical Education Consortium, Rockford, IL 61114, USA; (S.R.); (S.P.)
| | - Prashant Puttagunta
- Medical Education, University of Michigan Medical School, Ann Arbor, MI 48105, USA;
| | - Saagar Pamulapati
- Hematology-Oncology, Advocate Lutheran General Hospital, Park Ridge, IL 60068, USA;
| | - Jianqiang Yang
- Department of Hematology and Medical Oncology, Emory University, Atlanta, GA 30322, USA; (J.Y.)
- Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA
| | - Suneha Pocha
- Internal Medicine Program, Mercyhealth Graduate Medical Education Consortium, Rockford, IL 61114, USA; (S.R.); (S.P.)
| | - Nabil F. Saba
- Department of Hematology and Medical Oncology, Emory University, Atlanta, GA 30322, USA; (J.Y.)
- Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA
| | - Yong Teng
- Department of Hematology and Medical Oncology, Emory University, Atlanta, GA 30322, USA; (J.Y.)
- Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Emory University, Atlanta, GA 30322, USA
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Leung LL, Qu X, Chen B, Chan JYK. Extracellular vesicles in liquid biopsies: there is hope for oral squamous cell carcinoma. EXTRACELLULAR VESICLES AND CIRCULATING NUCLEIC ACIDS 2024; 5:639-659. [PMID: 39811735 PMCID: PMC11725428 DOI: 10.20517/evcna.2024.29] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 06/29/2024] [Accepted: 11/20/2024] [Indexed: 01/16/2025]
Abstract
Current approaches to oral cancer diagnosis primarily involve physical examination, tissue biopsy, and advanced computer-aided imaging techniques. However, despite these advances, patient survival rates have not significantly improved. Hence, there is a critical need to develop minimally invasive tools with high sensitivity and specificity to improve patient survival and quality of life. Liquid biopsy is a non-invasive, real-time method for predicting cancer status and potentially serves as a biomarker source for treatment response. Liquid biopsy includes rich biologically relevant components, such as circulating tumor cells, circulating tumor DNA, and extracellular vesicles (EVs). EVs are particularly intriguing due to their relatively high abundance in most biofluids, with the potential to identify specific cargo derived from circulating tumor EVs. Moreover, normal cells in lymph nodes can uptake EVs, fostering a pre-metastatic microenvironment that facilitates lymph node metastases - a common occurrence in oral cancers. This review encompasses English language publications over the last twenty years, focusing on methods for isolating EVs from saliva, blood, and lymphatic fluids, as well as the collection methods employed. Seventeen cases met the inclusion criteria according to ISEV guidelines, including 10 saliva cases, 6 blood cases, and 1 lymphatic fluid case. This review also highlighted research gaps in oral squamous cell carcinoma (OSCC) EVs, including a lack of multi-omics studies and the exploration of potential EV markers for drug resistance, as well as a notable underutilization of microfluidic technologies to translate liquid biopsy EV findings into clinical applications.
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Affiliation(s)
| | | | | | - Jason YK. Chan
- Department of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong 00000, China
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Dal Secco C, Tel A, Allegri L, Baldan F, Curcio F, Sembronio S, Faletra F, Robiony M, Damante G, Mio C. Longitudinal detection of somatic mutations in the saliva of head and neck squamous cell carcinoma-affected patients: a pilot study. Front Oncol 2024; 14:1480302. [PMID: 39555458 PMCID: PMC11564150 DOI: 10.3389/fonc.2024.1480302] [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: 08/13/2024] [Accepted: 10/15/2024] [Indexed: 11/19/2024] Open
Abstract
Introduction Liquid biopsy is gaining momentum for diagnosis and surveillance of cancer patients. Indeed, head and neck squamous cell carcinoma (HNSCC) is burdened with poor prognosis and high recurrence rates after treatment. It is therefore crucial to be able to detect minimal residual disease early after radical treatment or relapse, so surgery can be performed when the disease is still resectable. In this scenario, aim of this study is to create a liquid biopsy-based pipeline able to detect somatic tumor mutations in a cohort of HNSCC-affected patients undergoing follow-up after surgical intervention. Methods Our cohort included 17 patients diagnosed with HNSCC over 4 years. The first saliva sample was collected before surgery while the rest were collected during the subsequent visits, according to the follow-up schedule. Salivary DNA (sDNA) was extracted, and a 52-gene next generation sequencing (NGS)-based panel was used for somatic variants detection. Results 41.2% of samples collected before surgery bore a deleterious variant (n=7/17). Overall, 29.2% of samples harbored at least a pathogenic variant (n=21/72). The most frequently mutated genes were TP53 (80%), FBXW7 (8%), PDGFRA (4%) and PTEN (4%). Finally, three patients experienced a loco-regional relapse by clinical evaluations, anticipated in 67% of cases by the molecular one (n=2/3). Discussion Our data indicate that sDNA could aid in the monitoring of patients' follow-up as low-frequency somatic mutations could be assessed from the saliva of HNSCC patients. Prospectively, these results suggest that salivary-based liquid biopsy might pave the way for personalized molecular therapies based on mutational data.
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Affiliation(s)
- Chiara Dal Secco
- Department of Medicine (DMED), University of Udine, Udine, Italy
| | - Alessandro Tel
- Clinic of Maxillofacial Surgery, Head-Neck and NeuroScience Department, University Hospital of Udine, Udine, Italy
| | - Lorenzo Allegri
- Department of Medicine (DMED), University of Udine, Udine, Italy
| | - Federica Baldan
- Department of Medicine (DMED), University of Udine, Udine, Italy
| | - Francesco Curcio
- Department of Medicine (DMED), University of Udine, Udine, Italy
- Department of Laboratory Medicine, Institute of Clinical Pathology, University Hospital of Udine, Udine, Italy
| | - Salvatore Sembronio
- Department of Medicine (DMED), University of Udine, Udine, Italy
- Clinic of Maxillofacial Surgery, Head-Neck and NeuroScience Department, University Hospital of Udine, Udine, Italy
| | - Flavio Faletra
- Department of Laboratory Medicine, Institute of Medical Genetics, University Hospital of Udine, Udine, Italy
| | - Massimo Robiony
- Department of Medicine (DMED), University of Udine, Udine, Italy
- Clinic of Maxillofacial Surgery, Head-Neck and NeuroScience Department, University Hospital of Udine, Udine, Italy
| | - Giuseppe Damante
- Department of Medicine (DMED), University of Udine, Udine, Italy
- Department of Laboratory Medicine, Institute of Medical Genetics, University Hospital of Udine, Udine, Italy
| | - Catia Mio
- Department of Medicine (DMED), University of Udine, Udine, Italy
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Ahmed AA, Sborchia M, Bye H, Roman-Escorza M, Amar A, Henley-Smith R, Odell E, McGurk M, Simpson M, Ng T, Sawyer EJ, Mathew CG. Mutation detection in saliva from oral cancer patients. Oral Oncol 2024; 151:106717. [PMID: 38412584 PMCID: PMC11393295 DOI: 10.1016/j.oraloncology.2024.106717] [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: 10/25/2023] [Revised: 01/11/2024] [Accepted: 01/31/2024] [Indexed: 02/29/2024]
Abstract
OBJECTIVES The incidence of head and neck squamous cell carcinoma (HNSCC) continues to increase and although advances have been made in treatment, it still has a poor overall survival with local relapse being common. Conventional imaging methods are not efficient at detecting recurrence at an early stage when still potentially curable. The aim of this study was to test the feasibility of using saliva to detect the presence of oral squamous cell carcinoma (OSCC) and to provide additional evidence for the potential of this approach. MATERIALS AND METHODS Fresh tumor, whole blood and saliva were collected from patients with OSCC before treatment. Whole exome sequencing (WES) or gene panel sequencing of tumor DNA was performed to identify somatic mutations in tumors and to select genes for performing gene panel sequencing on saliva samples. RESULTS The most commonly mutated genes identified in primary tumors by DNA sequencing were TP53 and FAT1. Gene panel sequencing of paired saliva samples detected tumor derived mutations in 9 of 11 (82%) patients. The mean variant allele frequency for the mutations detected in saliva was 0.025 (range 0.004 - 0.061). CONCLUSION Somatic tumor mutations can be detected in saliva with high frequency in OSCC irrespective of site or stage of disease using a limited panel of genes. This work provides additional evidence for the suitability of using saliva as liquid biopsy in OSCC and has the potential to improve early detection of recurrence in OSCC. Trials are currently underway comparing this approach to standard imaging techniques.
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Affiliation(s)
- Ahmed A Ahmed
- School of Cancer and Pharmaceutical Sciences, Faculty of Life Sciences and Medicine, Guy's Cancer Centre, King's College London, London SE1 9RT, United Kingdom.
| | - Mateja Sborchia
- School of Cancer and Pharmaceutical Sciences, Faculty of Life Sciences and Medicine, Guy's Cancer Centre, King's College London, London SE1 9RT, United Kingdom
| | - Hannah Bye
- Department of Medical and Molecular Genetics, Faculty of Life Sciences and Medicine, King's College London, London SE1 9RT, United Kingdom
| | - Maria Roman-Escorza
- School of Cancer and Pharmaceutical Sciences, Faculty of Life Sciences and Medicine, Guy's Cancer Centre, King's College London, London SE1 9RT, United Kingdom
| | - Ariella Amar
- Department of Medical and Molecular Genetics, Faculty of Life Sciences and Medicine, King's College London, London SE1 9RT, United Kingdom
| | - Rhonda Henley-Smith
- KHP Head & Neck Cancer Biobank, Guy's & St Thomas' NHS Foundation Trust, Guy's Hospital, London SE1 9RT, United Kingdom
| | - Edward Odell
- King's College London and Head and Neck Pathology Guy's Hospital, London SE1 9RT, United Kingdom
| | - Mark McGurk
- Department of Head and Neck Surgery, University College London Hospital, London NW1 2BU, United Kingdom
| | - Michael Simpson
- Department of Medical and Molecular Genetics, Faculty of Life Sciences and Medicine, King's College London, London SE1 9RT, United Kingdom
| | - Tony Ng
- Richard Dimbleby Laboratory of Cancer Research, School of Cancer and Pharmaceutical Sciences, King's College London, Guy's Medical School Campus, London SE1 1UL, United Kingdom
| | - Elinor J Sawyer
- School of Cancer and Pharmaceutical Sciences, Faculty of Life Sciences and Medicine, Guy's Cancer Centre, King's College London, London SE1 9RT, United Kingdom
| | - Christopher G Mathew
- Department of Medical and Molecular Genetics, Faculty of Life Sciences and Medicine, King's College London, London SE1 9RT, United Kingdom; Sydney Brenner Institute for Molecular Bioscience, University of the Witwatersrand, Johannesburg, South Africa
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Chantre-Justino M, Figueiredo MC, Alves G, Ornellas MHF. A pilot study on salivary HPV DNA detection to monitor active disease from patients with recurrent respiratory papillomatosis. Am J Otolaryngol 2024; 45:104157. [PMID: 38061173 DOI: 10.1016/j.amjoto.2023.104157] [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: 10/01/2023] [Accepted: 12/04/2023] [Indexed: 03/16/2024]
Abstract
PURPOSE Recurrent respiratory papillomatosis (RRP) is a human papillomavirus (HPV)-related disease affecting the upper airway and saliva could be an important non-invasive sampling source for viral screening and clinical monitoring. We investigated whether HPV DNA could be detected in saliva (cellular pellets and supernatant) from RRP patients and influence on clinical manifestation of the disease. MATERIALS AND METHODS In this pilot study, saliva samples from 14 RRP patients were obtained in preoperative condition (n = 7) and in disease-free interval (DFI; n = 7). Healthy donors (n = 14) were also included. HPV DNA was investigated by polymerase chain reaction (PCR)-based assays. RESULTS From cellular pellets, HPV-positive saliva was only detected from preoperative collections (5/7; 71.4 %) and showed a mean cycle threshold (Ct) value of 24.33 (±1.25), whereas all patients in DFI were HPV-negative (Ct ≥ 32.16), revealing significant difference between these two clinical moments (p = 0.021). Patients in DFI and healthy donors showed similar Ct values. From saliva supernatant, detectable HPV cell-free DNA (cfDNA) occurred in 42.9 % (3/7) and 57.1 % (4/7) of preoperative collections using the commercial cfDNA kits from Norgen and Qiagen, respectively. Salivary cfDNA size distribution obtained by TapeStation analysis showed a predominant size range of 150 to 400 bp in both patients and healthy controls, corresponding to mononucleosomal and dinucleosomal fragments. CONCLUSIONS In conclusion, HPV DNA screening in saliva (both cellular pellets and cfDNA) may have clinical utility to monitor active disease of RRP patients.
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Affiliation(s)
- Mariana Chantre-Justino
- Circulating Biomarkers Laboratory, Pathology Department, Faculty of Medical Sciences, Rio de Janeiro State University, Rio de Janeiro 20550-170, Brazil; Research Division, National Institute of Traumatology and Orthopaedics (INTO), Rio de Janeiro 20940-070, Brazil.
| | - Marcelo Cardoso Figueiredo
- Respiratory Endoscopy and Head and Neck Surgery Service at Hospital Federal de Bonsucesso, Rio de Janeiro 21041-030, Brazil
| | - Gilda Alves
- Circulating Biomarkers Laboratory, Pathology Department, Faculty of Medical Sciences, Rio de Janeiro State University, Rio de Janeiro 20550-170, Brazil
| | - Maria Helena Faria Ornellas
- Circulating Biomarkers Laboratory, Pathology Department, Faculty of Medical Sciences, Rio de Janeiro State University, Rio de Janeiro 20550-170, Brazil
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Kumar P, Gupta S, Das BC. Saliva as a potential non-invasive liquid biopsy for early and easy diagnosis/prognosis of head and neck cancer. Transl Oncol 2024; 40:101827. [PMID: 38042138 PMCID: PMC10701368 DOI: 10.1016/j.tranon.2023.101827] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 11/03/2023] [Accepted: 11/07/2023] [Indexed: 12/04/2023] Open
Abstract
Head and neck squamous cell carcinomas (HNSCCs) are the most devastating diseases in India and southeast Asia. It is a preventable and curable disease if detected early. Tobacco and alcohol consumption are the two major risk-factors but infection of high-risk HPVs are also associated with development of predominantly oral and oropharyngeal carcinomas. Interestingly, unlike cervical cancer, HPV-induced HNSCCs show good prognosis and better survival in contrast, majority of tobacco-associated HPV-ve HNSCCs are highly aggressive with poor clinical outcome. Biomarker analysis in circulatory body-fluids for early cancer diagnosis, prognosis and treatment monitoring are becoming important in clinical practice. Early diagnosis using non-invasive saliva for oral or other diseases plays an important role in successful treatment and better prognosis. Saliva mirrors the body's state of health as it comes into direct contact with oral lesions and needs no trained manpower to collect, making it a suitable bio-fluid of choice for screening. Saliva can be used to detect not only virus, bacteria and other biomarkers but variety of molecular and genetic markers for an early detection, treatment and monitoring cancer and other diseases. The performance of saliva-based diagnostics are reported to be highly (≥95 %) sensitive and specific indicating the test's ability to correctly identify true positive or negative cases. This review focuses on the potentials of saliva in the early detection of not only HPV or other pathogens but also identification of highly reliable gene mutations, oral-microbiomes, metabolites, salivary cytokines, non-coding RNAs and exosomal miRNAs. It also discusses the importance of saliva as a reliable, cost-effective and an easy alternative to invasive procedures.
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Affiliation(s)
- Prabhat Kumar
- Stem Cell and Cancer Research Lab, Amity Institute of Molecular Medicine & Stem Cell Research (AIMMSCR), Amity University Uttar Pradesh, Sector-125, Noida 201313, India
| | - Shilpi Gupta
- Stem Cell and Cancer Research Lab, Amity Institute of Molecular Medicine & Stem Cell Research (AIMMSCR), Amity University Uttar Pradesh, Sector-125, Noida 201313, India
| | - Bhudev C Das
- Stem Cell and Cancer Research Lab, Amity Institute of Molecular Medicine & Stem Cell Research (AIMMSCR), Amity University Uttar Pradesh, Sector-125, Noida 201313, India.
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Huang X, Leo P, Jones L, Duijf PHG, Hartel G, Kenny L, Vasani S, Punyadeera C. A comparison between mutational profiles in tumour tissue DNA and circulating tumour DNA in head and neck squamous cell carcinoma - A systematic review. MUTATION RESEARCH. REVIEWS IN MUTATION RESEARCH 2024; 793:108477. [PMID: 37977279 DOI: 10.1016/j.mrrev.2023.108477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Revised: 11/10/2023] [Accepted: 11/13/2023] [Indexed: 11/19/2023]
Abstract
BACKGROUND Head and neck cancer is the seventh most common malignancy globally. Head and neck squamous cell carcinoma (HNSCC) originates from squamous cells and 90% of HNC are HNSCC. The gold standard for diagnosing HNSCC is tissue biopsy. However, given tumour heterogeneity, biopsies may miss important cancer-associated molecular signatures, and more importantly, after the tumour is excised, there is no means of tracking response to treatment in patients. Captured under liquid biopsy, circulating tumour DNA (ctDNA), may identify in vivo molecular genotypes and complements tumour tissue analysis in cancer management. A systematic search was conducted in PubMed, Embase, Scopus and the Cochran Library between 2012 to early 2023 on ctDNA in HNSCC using publications written in English. We summarise 20 studies that compared mutational profiles between tumour tissue DNA (tDNA) and ctDNA, using a cohort of 631 HNSCC patients and 139 controls. Among these studies, the concordance rates varied greatly and the most mutated and the most concordant gene was TP53, followed by PIK3CA, CDKN2A, NOTCH1 and FAT1. Concordant variants were mainly found in Stage IV tumours, and the mutation type is mostly single nucleotide variants (SNV). We conclude that, as a biomarker for HNSCC, ctDNA demonstrates great promise as it recapitulates tumour genotypes, however additional multi-central trials are needed.
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Affiliation(s)
- Xiaomin Huang
- Saliva and Liquid Biopsy Translational Laboratory, Griffith Institute for Drug Discovery, The School of Environment and Science, Griffith University, Brisbane, QLD, Australia
| | - Paul Leo
- School of Biomedical Science, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia; Center for Genomics and Personalised Health, Queensland University of Technology, Brisbane, QLD, Australia; Australian Translational Genomics Center, Brisbane, QLD, Australia
| | - Lee Jones
- QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; Research Methods Group, School of Public Health and Social Work, Queensland University of Technology, Kelvin Grove, Brisbane, QLD, Australia
| | - Pascal H G Duijf
- School of Biomedical Science, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia; Center for Genomics and Personalised Health, Queensland University of Technology, Brisbane, QLD, Australia; Centre for Cancer Biology, Clinical and Health Sciences, University of South Australia & SA Pathology, Adelaide, SA, Australia; Department of Medical Genetics, Oslo University Hospital, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway
| | - Gunter Hartel
- QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
| | - Lizbeth Kenny
- School of Medicine, University of Queensland, Brisbane, QLD, Australia; Cancer Care Service, Royal Brisbane Women's Hospital, Brisbane, QLD, Australia
| | - Sarju Vasani
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway; Department of Otolaryngology, Royal Brisbane Women's Hospital, Brisbane, QLD, Australia
| | - Chamindie Punyadeera
- Saliva and Liquid Biopsy Translational Laboratory, Griffith Institute for Drug Discovery, The School of Environment and Science, Griffith University, Brisbane, QLD, Australia; Menzies Health Institute Queensland, Griffith University, QLD, Australia.
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9
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Wu Y, Pei J, Li Y, Wang G, Li L, Liu J, Tian G. High-sensitive and rapid electrochemical detection of miRNA-31 in saliva using Cas12a-based 3D nano-harvester with improved trans-cleavage efficiency. Talanta 2024; 266:125066. [PMID: 37579676 DOI: 10.1016/j.talanta.2023.125066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 05/11/2023] [Accepted: 08/07/2023] [Indexed: 08/16/2023]
Abstract
Salivary miRNA-31 is a reliable diagnostic marker for early-stage oral squamous cell carcinoma (OSCC), but accurate detection of miRNA-31 in saliva samples is a challenge because of its low level and high sequence homology. The CRISPR/Cas12a system has the exceptional potential to enable simple nucleic acid analysis but suffers from low speed and sensitivity. To achieve rapid and high-sensitive detection of miRNA-31 using the CRISPR/Cas12a system, a Cas12a-based nano-harvester activated by a polymerase-driven DNA walker, named as dual 3D nanorobots, was developed. The target walked rapidly on the surface of DNA hairpin-modified magnetic nanoparticles driven by DNA polymerase, generating numerous double-strand DNA (dsDNA). Then, the Cas12a bound to the generated dsDNA for activating its trans-cleavage activity, forming 3D nano-harvester. Subsequently, the harvester cut and released methylene blue-labeled DNA hairpins immobilized on the sensing interface, leading to the change in electrochemical signal. We found that the trans-cleavage activity of the harvester was higher than the conventional CRISPR/Cas12a system. The developed dual 3D nanorobots could enable rapid (detection time within 60 min), high-sensitive (detection limit of femtomolar), and specific analysis of miRNA-31 in saliva samples. Thus, our established electrochemical biosensing strategy has great potential for early diagnosis of OSCC.
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Affiliation(s)
- Yu Wu
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China
| | - Jingwen Pei
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China
| | - Yi Li
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China
| | - Guobin Wang
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China
| | - Lan Li
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China
| | - Jinbo Liu
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China.
| | - Gang Tian
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China.
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Zavarykina TM, Lomskova PK, Pronina IV, Khokhlova SV, Stenina MB, Sukhikh GT. Circulating Tumor DNA Is a Variant of Liquid Biopsy with Predictive and Prognostic Clinical Value in Breast Cancer Patients. Int J Mol Sci 2023; 24:17073. [PMID: 38069396 PMCID: PMC10706922 DOI: 10.3390/ijms242317073] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 11/24/2023] [Accepted: 11/27/2023] [Indexed: 12/18/2023] Open
Abstract
This paper introduces the reader to the field of liquid biopsies and cell-free nucleic acids, focusing on circulating tumor DNA (ctDNA) in breast cancer (BC). BC is the most common type of cancer in women, and progress with regard to treatment has been made in recent years. Despite this, there remain a number of unresolved issues in the treatment of BC; in particular, early detection and diagnosis, reliable markers of response to treatment and for the prediction of recurrence and metastasis, especially for unfavorable subtypes, are needed. It is also important to identify biomarkers for the assessment of drug resistance and for disease monitoring. Our work is devoted to ctDNA, which may be such a marker. Here, we describe its main characteristics and potential applications in clinical oncology. This review considers the results of studies devoted to the analysis of the prognostic and predictive roles of various methods for the determination of ctDNA in BC patients. Currently known epigenetic changes in ctDNA with clinical significance are reviewed. The possibility of using ctDNA as a predictive and prognostic marker for monitoring BC and predicting the recurrence and metastasis of cancer is also discussed, which may become an important part of a precision approach to the treatment of BC.
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Affiliation(s)
- Tatiana M. Zavarykina
- N.M. Emanuel Institute of Biochemical Physics of the Russian Academy of Sciences, Moscow 119334, Russia;
- “B.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology of Ministry of Health of the Russian Federation, Moscow 117997, Russia; (S.V.K.); (G.T.S.)
| | - Polina K. Lomskova
- N.M. Emanuel Institute of Biochemical Physics of the Russian Academy of Sciences, Moscow 119334, Russia;
| | - Irina V. Pronina
- Institute of General Pathology and Pathophysiology, Moscow 125315, Russia;
| | - Svetlana V. Khokhlova
- “B.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology of Ministry of Health of the Russian Federation, Moscow 117997, Russia; (S.V.K.); (G.T.S.)
| | - Marina B. Stenina
- “N.N. Blokhin National Medical Research Center of Oncology of Ministry of Health of the Russian Federation, Moscow 115522, Russia;
| | - Gennady T. Sukhikh
- “B.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology of Ministry of Health of the Russian Federation, Moscow 117997, Russia; (S.V.K.); (G.T.S.)
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Rapado-González Ó, Rodríguez-Ces AM, López-López R, Suárez-Cunqueiro MM. Liquid biopsies based on cell-free DNA as a potential biomarker in head and neck cancer. JAPANESE DENTAL SCIENCE REVIEW 2023; 59:289-302. [PMID: 37680614 PMCID: PMC10480573 DOI: 10.1016/j.jdsr.2023.08.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Revised: 07/31/2023] [Accepted: 08/17/2023] [Indexed: 09/09/2023] Open
Abstract
In the era of 'precision medicine', liquid biopsies based on cell-free DNA (cfDNA) have emerged as a promising tool in the oncology field. cfDNA from cancer patients is a mixture of tumoral (ctDNA) and non-tumoral DNA originated from healthy, cancer and tumor microenvironmental cells. Apoptosis, necrosis, and active secretion from extracellular vesicles represent the main mechanisms of cfDNA release into the physiological body fluids. Focused on HNC, two main types of cfDNA can be identified: the circulating cfDNA (ccfDNA) and the salivary cfDNA (scfDNA). Numerous studies have reported on the potential of cfDNA analysis as potential diagnostic, prognostic, and monitoring biomarker for HNC. Thus, ctDNA has emerged as an attractive strategy to detect cancer specific genetic and epigenetic alterations including DNA somatic mutations and DNA methylation patterns. This review aims to provide an overview of the up-to-date studies evaluating the value of the analysis of total cfDNA, cfDNA fragment length, and ctDNA analysis at DNA mutation and methylation level in HNC patients.
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Affiliation(s)
- Óscar Rapado-González
- Department of Surgery and Medical-Surgical Specialties, Medicine and Dentistry School, Universidade de Santiago de Compostela (USC), 15782 Santiago de Compostela, Spain
- Galician Precision Oncology Research Group (ONCOGAL), Medicine and Dentistry School, Universidade de Santiago de Compostela (USC), Santiago de Compostela, Spain
- Liquid Biopsy Analysis Unit, Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago (IDIS), Santiago de Compostela, Spain
- Centro de Investigación Biomédica en Red en Cáncer (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Ana María Rodríguez-Ces
- Department of Surgery and Medical-Surgical Specialties, Medicine and Dentistry School, Universidade de Santiago de Compostela (USC), 15782 Santiago de Compostela, Spain
- Galician Precision Oncology Research Group (ONCOGAL), Medicine and Dentistry School, Universidade de Santiago de Compostela (USC), Santiago de Compostela, Spain
- Liquid Biopsy Analysis Unit, Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago (IDIS), Santiago de Compostela, Spain
| | - Rafael López-López
- Centro de Investigación Biomédica en Red en Cáncer (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago (IDIS), Complexo Hospitalario Universitario de Santiago de Compostela (CHUS, SERGAS), 15706 Santiago de Compostela, Spain
| | - María Mercedes Suárez-Cunqueiro
- Department of Surgery and Medical-Surgical Specialties, Medicine and Dentistry School, Universidade de Santiago de Compostela (USC), 15782 Santiago de Compostela, Spain
- Galician Precision Oncology Research Group (ONCOGAL), Medicine and Dentistry School, Universidade de Santiago de Compostela (USC), Santiago de Compostela, Spain
- Centro de Investigación Biomédica en Red en Cáncer (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago (IDIS), Complexo Hospitalario Universitario de Santiago de Compostela (CHUS, SERGAS), 15706 Santiago de Compostela, Spain
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Lin LH, Chang KW, Cheng HW, Liu CJ. Identification of Somatic Mutations in Plasma Cell-Free DNA from Patients with Metastatic Oral Squamous Cell Carcinoma. Int J Mol Sci 2023; 24:10408. [PMID: 37373553 DOI: 10.3390/ijms241210408] [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: 05/08/2023] [Revised: 06/01/2023] [Accepted: 06/15/2023] [Indexed: 06/29/2023] Open
Abstract
The accurate diagnosis and treatment of oral squamous cell carcinoma (OSCC) requires an understanding of its genomic alterations. Liquid biopsies, especially cell-free DNA (cfDNA) analysis, are a minimally invasive technique used for genomic profiling. We conducted comprehensive whole-exome sequencing (WES) of 50 paired OSCC cell-free plasma with whole blood samples using multiple mutation calling pipelines and filtering criteria. Integrative Genomics Viewer (IGV) was used to validate somatic mutations. Mutation burden and mutant genes were correlated to clinico-pathological parameters. The plasma mutation burden of cfDNA was significantly associated with clinical staging and distant metastasis status. The genes TTN, PLEC, SYNE1, and USH2A were most frequently mutated in OSCC, and known driver genes, including KMT2D, LRP1B, TRRAP, and FLNA, were also significantly and frequently mutated. Additionally, the novel mutated genes CCDC168, HMCN2, STARD9, and CRAMP1 were significantly and frequently present in patients with OSCC. The mutated genes most frequently found in patients with metastatic OSCC were RORC, SLC49A3, and NUMBL. Further analysis revealed that branched-chain amino acid (BCAA) catabolism, extracellular matrix-receptor interaction, and the hypoxia-related pathway were associated with OSCC prognosis. Choline metabolism in cancer, O-glycan biosynthesis, and protein processing in the endoplasmic reticulum pathway were associated with distant metastatic status. About 20% of tumors carried at least one aberrant event in BCAA catabolism signaling that could possibly be targeted by an approved therapeutic agent. We identified molecular-level OSCC that were correlated with etiology and prognosis while defining the landscape of major altered events of the OSCC plasma genome. These findings will be useful in the design of clinical trials for targeted therapies and the stratification of patients with OSCC according to therapeutic efficacy.
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Affiliation(s)
- Li-Han Lin
- Department of Medical Research, MacKay Memorial Hospital No. 92, Sec. 2, Chung San N. Rd., Taipei 10449, Taiwan
| | - Kuo-Wei Chang
- Institute of Oral Biology, School of Dentistry, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan
- Department of Stomatology, Taipei Veterans General Hospital, Taipei 11121, Taiwan
| | - Hui-Wen Cheng
- Department of Medical Research, MacKay Memorial Hospital No. 92, Sec. 2, Chung San N. Rd., Taipei 10449, Taiwan
| | - Chung-Ji Liu
- Department of Medical Research, MacKay Memorial Hospital No. 92, Sec. 2, Chung San N. Rd., Taipei 10449, Taiwan
- Institute of Oral Biology, School of Dentistry, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan
- Department of Oral and Maxillofacial Surgery, Taipei MacKay Memorial Hospital, Taipei 10449, Taiwan
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Xi Y, Negrao MV, Akagi K, Xiao W, Jiang B, Warner SC, Dunn JD, Wang J, Symer DE, Gillison ML. Noninvasive genomic profiling of somatic mutations in oral cavity cancers. Oral Oncol 2023; 140:106372. [PMID: 37004423 PMCID: PMC10367182 DOI: 10.1016/j.oraloncology.2023.106372] [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: 09/06/2022] [Revised: 02/13/2023] [Accepted: 03/21/2023] [Indexed: 04/03/2023]
Abstract
OBJECTIVES Somatic mutations may predict prognosis, therapeutic response, or cancer progression. We evaluated targeted sequencing of oral rinse samples (ORS) for non-invasive mutational profiling of oral squamous cell carcinomas (OSCC). MATERIALS AND METHODS A custom hybrid capture panel targeting 42 frequently mutated genes in OSCC was used to identify DNA sequence variants in matched ORS and fresh-frozen tumors from 120 newly-diagnosed patients. Receiver operating characteristic (ROC) curves determined the optimal variant allele fraction (VAF) cutoff for variant discrimination in ORS. Behavioral, clinical, and analytical factors were evaluated for impacts on assay performance. RESULTS Half of tumors involved oral tongue (50 %), and a majority were T1-T2 tumor stage (55 %). Median depth of sequencing coverage was 260X for OSCC and 1,563X for ORS. Frequencies of single nucleotide variants (SNVs) at highly mutated genes (including TP53, FAT1, HRAS, NOTCH1, CDKN2A, CASP8, NFE2L2, and PIK3CA) in OSCC were highly correlated with TCGA data (R = 0.96, p = 2.5E-22). An ROC curve with area-under-the-curve (AUC) of 0.80 showed that, at an optimal VAF cutoff of 0.10 %, ORS provided 76 % sensitivity, 96 % specificity, but precision of only 2.6E-4. At this VAF cutoff, 206 of 270 SNVs in OSCC were detected in matched ORS. Sensitivity varied by patient, T stage and target gene. Neither downsampled ORS as matched control nor a naïve Bayesian classifier adjusting for sequencing bias appreciably improved assay performance. CONCLUSION Targeted sequencing of ORS provides moderate assay performance for noninvasive detection of SNVs in OSCC. Our findings strongly rationalize further clinical and laboratory optimization of this assay, including strategies to improve precision.
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Affiliation(s)
- Yuanxin Xi
- Department of Bioinformatics & Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Marcelo V Negrao
- Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Keiko Akagi
- Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Weihong Xiao
- Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Bo Jiang
- Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Sarah C Warner
- Genomics Shared Resource, The Ohio State University, Columbus, OH, United States
| | - Joe Dan Dunn
- Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Jing Wang
- Department of Bioinformatics & Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - David E Symer
- Department of Lymphoma & Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
| | - Maura L Gillison
- Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
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Li P, Liu S, Du L, Mohseni G, Zhang Y, Wang C. Liquid biopsies based on DNA methylation as biomarkers for the detection and prognosis of lung cancer. Clin Epigenetics 2022; 14:118. [PMID: 36153611 PMCID: PMC9509651 DOI: 10.1186/s13148-022-01337-0] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2022] [Accepted: 09/16/2022] [Indexed: 11/27/2022] Open
Abstract
Lung cancer (LC) is the main cause of cancer-related mortality. Most LC patients are diagnosed in an advanced stage when the symptoms are obvious, and the prognosis is quite poor. Although low-dose computed tomography (LDCT) is a routine clinical examination for early detection of LC, the false-positive rate is over 90%. As one of the intensely studied epigenetic modifications, DNA methylation plays a key role in various diseases, including cancer and other diseases. Hypermethylation in tumor suppressor genes or hypomethylation in oncogenes is an important event in tumorigenesis. Remarkably, DNA methylation usually occurs in the very early stage of malignant tumors. Thus, DNA methylation analysis may provide some useful information about the early detection of LC. In recent years, liquid biopsy has developed rapidly. Liquid biopsy can detect and monitor both primary and metastatic malignant tumors and can reflect tumor heterogeneity. Moreover, it is a minimally invasive procedure, and it causes less pain for patients. This review summarized various liquid biopsies based on DNA methylation for LC. At first, we briefly discussed some emerging technologies for DNA methylation analysis. Subsequently, we outlined cell-free DNA (cfDNA), sputum, bronchoalveolar lavage fluid, bronchial aspirates, and bronchial washings DNA methylation-based liquid biopsy for the early detection of LC. Finally, the prognostic value of DNA methylation in cfDNA and sputum and the diagnostic value of other DNA methylation-based liquid biopsies for LC were also analyzed.
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Abstract
Somatic mutations of genes involved in NF-κB, PI3K/AKT, NOTCH, and JAK/STAT signaling pathways play an important role in the pathogenesis of Hodgkin lymphoma (HL). HL tumor cells form only about 5% of the tumor mass; however, it was shown that HL tumor-derived DNA could be detected in the bloodstream. This circulating tumor DNA (ctDNA) reflects the genetic profile of HL tumor cells and can be used for qualitative and quantitative analysis of tumor-specific somatic DNA mutations within the concept of liquid biopsy. Overall, the most frequently mutated gene in HL is STAT6; however, the exact spectrum of mutations differs between individual HL histological subtypes. Importantly, reduction of ctDNA plasma levels after initial treatment is highly correlated with prognosis. Therefore, ctDNA shows great promise as a novel tool for non-invasive tumor genome analysis for biomarker driven therapy as well as for superior minimal residual disease monitoring and treatment resistance detection. Here, we summarize the recent advancements of ctDNA analysis in HL with focus on ctDNA detection methodologies, genetic profiling of HL and its clonal evolution, and the emerging prognostic value of ctDNA.
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Chantre-Justino M, Alves G, Delmonico L. Clinical applications of liquid biopsy in HPV‐negative and HPV‐positive head and neck squamous cell carcinoma: advances and challenges. EXPLORATION OF TARGETED ANTI-TUMOR THERAPY 2022; 3:533-552. [PMID: 36071985 PMCID: PMC9446158 DOI: 10.37349/etat.2022.00099] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Accepted: 06/22/2022] [Indexed: 12/02/2022] Open
Abstract
Head and neck squamous cell carcinomas (HNSCCs) represent the most common epithelial tumors that arise from mucosa of the oral cavity, pharynx, and larynx. The development of HNSCCs is usually associated with tobacco use, alcohol consumption, and human papillomavirus (HPV) infection. Most HNSCCs are diagnosed in advanced states, leading to a worse clinical outcome. Screening tests based on potential biomarkers associated with HNSCCs could improve this scenario. Liquid biopsy has emerged as a promising area of cancer investigation, offering a minimally invasive approach to track circulating biomarkers in body fluids that could potentially contribute to the diagnosis, predict prognosis, and monitor response to treatment. This review will discuss translational studies describing the clinical applications of liquid biopsy in HPV-negative and HPV-positive HNSCCs focused on circulating nucleic acids [cell-free DNA (cfDNA) and cell-free RNA (cfRNA)], circulating tumor cells (CTCs), and extracellular vesicles (EVs), which can be found in plasma, serum, and saliva.
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Affiliation(s)
- Mariana Chantre-Justino
- 1Research Division, National Institute of Traumatology and Orthopaedics (INTO), Rio de Janeiro 20940-070, Brazil 2Circulating Biomarkers Laboratory, Pathology Department, Faculty of Medical Sciences, Rio de Janeiro State University, Rio de Janeiro 20550-170, Brazil
| | - Gilda Alves
- 2Circulating Biomarkers Laboratory, Pathology Department, Faculty of Medical Sciences, Rio de Janeiro State University, Rio de Janeiro 20550-170, Brazil
| | - Lucas Delmonico
- 3Oncoclínicas Precision Medicine, Vila Nova Conceição, São Paulo 04513-020, Brazil
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Liquid Biopsy and Circulating Biomarkers for the Diagnosis of Precancerous and Cancerous Oral Lesions. Noncoding RNA 2022; 8:ncrna8040060. [PMID: 36005828 PMCID: PMC9414906 DOI: 10.3390/ncrna8040060] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 07/21/2022] [Accepted: 08/08/2022] [Indexed: 12/19/2022] Open
Abstract
Oral cancer is one of the most common malignancies worldwide, accounting for 2% of all cases annually and 1.8% of all cancer deaths. To date, tissue biopsy and histopathological analyses are the gold standard methods for the diagnosis of oral cancers. However, oral cancer is generally diagnosed at advanced stages with a consequent poor 5-year survival (~50%) due to limited screening programs and inefficient physical examination strategies. To address these limitations, liquid biopsy is recently emerging as a novel minimally invasive tool for the early identification of tumors as well as for the evaluation of tumor heterogeneity and prognosis of patients. Several studies have demonstrated that liquid biopsy in oral cancer could be useful for the detection of circulating biomarkers including circulating tumor DNA (ctDNA), microRNAs (miRNAs), proteins, and exosomes, thus improving diagnostic strategies and paving the way to personalized medicine. However, the application of liquid biopsy in oral cancer is still limited and further studies are needed to better clarify its clinical impact. The present manuscript aims to provide an updated overview of the potential use of liquid biopsy as an additional tool for the management of oral lesions by describing the available methodologies and the most promising biomarkers.
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The implications of gene mutations in salivary DNA for noninvasive diagnosis of head and neck cancer with a focus on oral cancer. Oral Oncol 2022; 130:105924. [PMID: 35594773 DOI: 10.1016/j.oraloncology.2022.105924] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 05/10/2022] [Indexed: 12/16/2022]
Abstract
DNA-based liquid biopsy as a diagnostic strategy of head and neck squamous cell carcinoma (HNSCC) has emergingly gained momentum. In this letter, we identified 6 studies contained 274 patients with HNSCC focused on gene mutations in salivary DNA. We observe that the incidence of DNA mutations with at least one gene mutated ranges from 63% to 95.9%, and the most frequently examined gene mutations are TP53, CDKN2A, PIK3CA, FAT1, and NOTCH1. Meanwhile, studies have demonstrated that saliva had a greater sensitivity and much higher quantitative values than plasma in both tumor DNA count and variant allele frequency. Interestingly, more tumor-derived mutations were detected in salivary DNA among patients with tumors arising in oral cavity compared to in oropharynx, larynx, and hypopharynx. Collectively, it is feasibility to identify somatic mutations in driver genes using saliva samples to noninvasively diagnose HNSCC, especially in oral cavity cancer and even at early stages of the disease. Larger well-designed studies are needed to consolidate the evidence.
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Yang X, Xu X, Zhang C, Ji T, Wan T, Liu W. The diagnostic value and prospects of gene mutations in circulating tumor DNA for head and neck cancer monitoring. Oral Oncol 2022; 128:105846. [DOI: 10.1016/j.oraloncology.2022.105846] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 03/24/2022] [Indexed: 10/18/2022]
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Shabbir A, Waheed H, Ahmed S, Shaikh SS, Farooqui WA. Association of salivary Cathepsin B in different histological grades among patients presenting with oral squamous cell carcinoma. BMC Oral Health 2022; 22:63. [PMID: 35260133 PMCID: PMC8905853 DOI: 10.1186/s12903-022-02052-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2021] [Accepted: 01/11/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Oral cancer is considered a major public health problem due to its high mortality and morbidity rates. Survival rate of OSCC can be significantly improved by using non-invasive tool such as salivary biomarkers for detection of OSCC which is considered a promising approach. Cathepsin B is a lysosomal cysteine protease, present in abundant quantities in lysosome of cells, tissues and different biological fluids. Increased expression of Cathepsin B was observed in many malignancies including oral cancer. The present study was designed to determine the salivary levels of Cathepsin B in different histological grades of OSCC. METHOD In this study, total no. of 80 research participants were enrolled which were divided into four groups. Each group comprised 20 participants, group 1 comprised 20 patients of OSCC (well differentiated), group 2 comprised 20 patients of OSCC (moderately differentiated), group 3 comprised 20 patients of OSCC (poorly differentiated) and group 4 comprised 20 healthy controls. Saliva sample was collected from all the four study groups and salivary Cathepsin B levels were analyzed by ELISA sandwich technique in duplicate. RESULTS Salivary levels of Cathepsin B were significantly increased with p value (< 0.001) in patients of OSCC as compared to control group according to both histological grades and tumor size. Highest mean Cathepsin B levels in well differentiated OSCC followed by poorly differentiated OSCC and moderately differentiated OSCC were observed. CONCLUSION Results of the present study suggests that Cathepsin B has a great value as a salivary biomarker for diagnosis and monitoring of OSCC in different histological grades. This will further lead to increase survival rate and improve the prognosis of OSCC.
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Affiliation(s)
- Alveena Shabbir
- Department of Oral Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | - Humera Waheed
- Department of Dow College of Biotechnology, Dow University of Health Sciences, Karachi, Pakistan.
| | - Shaheen Ahmed
- Department of Oral and Maxillofacial Surgery, Dow University of Health Sciences, Karachi, Pakistan.
| | | | - Waqas Ahmed Farooqui
- Department of School of Public Health, Dow University of Health Sciences, Karachi, Pakistan
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Diez-Fraile A, De Ceulaer J, Derpoorter C, Spaas C, De Backer T, Lamoral P, Abeloos J, Lammens T. Tracking the Molecular Fingerprint of Head and Neck Cancer for Recurrence Detection in Liquid Biopsies. Int J Mol Sci 2022; 23:ijms23052403. [PMID: 35269544 PMCID: PMC8910330 DOI: 10.3390/ijms23052403] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Revised: 02/17/2022] [Accepted: 02/19/2022] [Indexed: 02/04/2023] Open
Abstract
The 5-year relative survival for patients with head and neck cancer, the seventh most common form of cancer worldwide, was reported as 67% in developed countries in the second decade of the new millennium. Although surgery, radiotherapy, chemotherapy, or combined treatment often elicits an initial satisfactory response, relapses are frequently observed within two years. Current surveillance methods, including clinical exams and imaging evaluations, have not unambiguously demonstrated a survival benefit, most probably due to a lack of sensitivity in detecting very early recurrence. Recently, liquid biopsy monitoring of the molecular fingerprint of head and neck squamous cell carcinoma has been proposed and investigated as a strategy for longitudinal patient care. These innovative methods offer rapid, safe, and highly informative genetic analysis that can identify small tumors not yet visible by advanced imaging techniques, thus potentially shortening the time to treatment and improving survival outcomes. In this review, we provide insights into the available evidence that the molecular tumor fingerprint can be used in the surveillance of head and neck squamous cell carcinoma. Challenges to overcome, prior to clinical implementation, are also discussed.
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Affiliation(s)
- Araceli Diez-Fraile
- Division of Oral and Maxillofacial Surgery, Department of Surgery, General Hospital Sint-Jan Brugge-Oostende A.V., 8000 Bruges, Belgium; (A.D.-F.); (J.D.C.); (C.S.); (T.D.B.); (P.L.); (J.A.)
| | - Joke De Ceulaer
- Division of Oral and Maxillofacial Surgery, Department of Surgery, General Hospital Sint-Jan Brugge-Oostende A.V., 8000 Bruges, Belgium; (A.D.-F.); (J.D.C.); (C.S.); (T.D.B.); (P.L.); (J.A.)
| | - Charlotte Derpoorter
- Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, 9000 Ghent, Belgium;
- Department of Internal Medicine and Pediatrics, Ghent University, 9000 Ghent, Belgium
- Cancer Research Institute Ghent (C.R.I.G.), 9000 Ghent, Belgium
| | - Christophe Spaas
- Division of Oral and Maxillofacial Surgery, Department of Surgery, General Hospital Sint-Jan Brugge-Oostende A.V., 8000 Bruges, Belgium; (A.D.-F.); (J.D.C.); (C.S.); (T.D.B.); (P.L.); (J.A.)
| | - Tom De Backer
- Division of Oral and Maxillofacial Surgery, Department of Surgery, General Hospital Sint-Jan Brugge-Oostende A.V., 8000 Bruges, Belgium; (A.D.-F.); (J.D.C.); (C.S.); (T.D.B.); (P.L.); (J.A.)
| | - Philippe Lamoral
- Division of Oral and Maxillofacial Surgery, Department of Surgery, General Hospital Sint-Jan Brugge-Oostende A.V., 8000 Bruges, Belgium; (A.D.-F.); (J.D.C.); (C.S.); (T.D.B.); (P.L.); (J.A.)
| | - Johan Abeloos
- Division of Oral and Maxillofacial Surgery, Department of Surgery, General Hospital Sint-Jan Brugge-Oostende A.V., 8000 Bruges, Belgium; (A.D.-F.); (J.D.C.); (C.S.); (T.D.B.); (P.L.); (J.A.)
| | - Tim Lammens
- Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, 9000 Ghent, Belgium;
- Department of Internal Medicine and Pediatrics, Ghent University, 9000 Ghent, Belgium
- Cancer Research Institute Ghent (C.R.I.G.), 9000 Ghent, Belgium
- Correspondence: ; Tel.: +32-9-332-2480
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