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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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Li Y, Fan L, Yan A, Ren X, Zhao Y, Hua B. Exosomal miR-361-3p promotes the viability of breast cancer cells by targeting ETV7 and BATF2 to upregulate the PAI-1/ERK pathway. J Transl Med 2024; 22:112. [PMID: 38282047 PMCID: PMC10823750 DOI: 10.1186/s12967-024-04914-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 01/21/2024] [Indexed: 01/30/2024] Open
Abstract
BACKGROUND Malignant progression is the major cause of poor prognosis in breast cancer (BC) patients. Plasma exosomal miRNAs have been reported to be involved in tumor progression, but their roles in BC remain unclear. METHODS We performed plasma exosomal miRNA sequencing on 45 individuals, including healthy controls and nonmetastatic and metastatic BC patients. We examined the correlation between miRNA expression in tumor tissues and plasma exosomes in BC patients by qRT‒PCR. The effects of exosomal miR-361-3p on BC cells were determined by CellTiter-Glo, migration and wound healing assays. The target genes of miR-361-3p and downstream pathways were explored by dual-luciferase reporter assay, RNA knockdown, rescue experiments, and western blotting. We utilized murine xenograft model to further assess the impact of plasma exosomal miR-361-3p on the malignant progression of BC. RESULTS We found that the expression level of plasma exosomal miR-361-3p gradually increased with malignant progression in BC patients, and the expression of miR-361-3p in plasma exosomes and BC tissues was positively correlated. Consistently, exosomal miR-361-3p enhanced the migration and proliferation of two BC cell lines, MDA-MB-231 and SK-BR-3. Furthermore, our data showed that miR-361-3p inhibited two novel target genes, ETV7 and BATF2, to activate the PAI-1/ERK pathway, leading to increased BC cell viability. Finally, the consistency of the in vivo experimental results supported that elevated plasma exosomal miR-361-3p promote the malignant progression of BC. CONCLUSIONS We found for the first time that plasma exosomal miR-361-3p was associated with malignant progression in BC patients. Mechanistically, exosomal miR-361-3p can enhance the migration and proliferation of BC cells by targeting the ETV7 and BATF2/PAI-1/ERK pathways. Our data suggest that plasma exosomal miR-361-3p has the potential to serve as a biomarker for predicting malignant progression in BC patients.
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Affiliation(s)
- Yao Li
- Breast center, Department of Thyroid-Breast-Hernia Surgery, Department of General Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Lei Fan
- Breast center, Department of Thyroid-Breast-Hernia Surgery, Department of General Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - An Yan
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing, People's Republic of China
| | - Xiaotian Ren
- Breast center, Department of Thyroid-Breast-Hernia Surgery, Department of General Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Yanyang Zhao
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing, People's Republic of China
| | - Bin Hua
- Breast center, Department of Thyroid-Breast-Hernia Surgery, Department of General Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
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Jayaraman S, Natarajan SR, Veeraraghavan VP, Jasmine S. Unveiling the anti-cancer mechanisms of calotropin: Insights into cell growth inhibition, cell cycle arrest, and metabolic regulation in human oral squamous carcinoma cells (HSC-3). J Oral Biol Craniofac Res 2023; 13:704-713. [PMID: 37731845 PMCID: PMC10507650 DOI: 10.1016/j.jobcr.2023.09.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 08/23/2023] [Accepted: 09/09/2023] [Indexed: 09/22/2023] Open
Abstract
Background Calotropin, a cardiac glycoside obtained from the plant Calotropis gigantea, has demonstrated promising potential as an anti-tumorigenesis compound. Objective The main objective of this study was to investigate the potential anti-cancer properties of calotropin against HSC-3 oral squamous cancer cells and to elucidate the underlying mechanisms involved in its action. Material and method Calotropin were treated in HSC-3 to evaluate cell viability by MTT assay. Flow cytometry analysis divulged that calotropin G0/G1 phase cell cycle arrest and apoptosis in HSC-3 cells. Calotropin displayed inhibitory properties against aerobic glycolysis, a metabolic alteration using glucose uptaken, lactose production and LDHA activity assays. Furthermore, migration and invasion assays help that calotropin has ability to reduce the migratory and invasive of HSC-3 cells, using transwell and Matrigel assay. Validation of mRNA expression through RT-PCR. Molecular docking was implemented to validate the binding association of calotropin with apoptosis and metastatic regulating targets. Result The results exemplify that increasing doses of calotropin effectively hold back the HSC-3 cell progression. Migration and invasion assays help that calotropin has ability to reduce the migratory and invasive of HSC-3 cells, indicating its potential to inhibit cancer metastasis. These results imply that calotropin may influence genes linked to metastasis and apoptosis in order to achieve its beneficial effects on cancer. Docking results provided further support, showing a high binding energy between calotropin and metastasis-mediated pathways. Conclusion Overall, our findings shed an experimental evidence on how calotropin inhibits the HSC-3 oral squamous cancer cell growth, highlighting the drug's potential as a treatment for oral cancer. Further, investigation on in-vivo experiment is warranted to explore its potential mechanism of action and to develop a novel drug towards clinical trial.
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Affiliation(s)
- Selvaraj Jayaraman
- Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College & Hospitals, Saveetha Institute of Medical & Technical Sciences, Saveetha University, Chennai, 600077, India
| | - Sathan Raj Natarajan
- Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College & Hospitals, Saveetha Institute of Medical & Technical Sciences, Saveetha University, Chennai, 600077, India
| | - Vishnu Priya Veeraraghavan
- Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College & Hospitals, Saveetha Institute of Medical & Technical Sciences, Saveetha University, Chennai, 600077, India
| | - Sharmila Jasmine
- Department of Oral Maxillofacial Surgery, Rajas Dental College and Hospital, Kavalkinaru, Tirunelveli, 627105, Tamil Nadu, India
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Ahmadi N, Kelly G, Low TH(H, Clark J, Gupta R. Molecular factors governing perineural invasion in malignancy. Surg Oncol 2022; 42:101770. [PMID: 35490532 DOI: 10.1016/j.suronc.2022.101770] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 03/27/2022] [Accepted: 04/10/2022] [Indexed: 12/30/2022]
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Identification of Candidate Target Genes and Immune Cells in Oral Squamous Cell Carcinoma. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2021:5802110. [PMID: 35003322 PMCID: PMC8739923 DOI: 10.1155/2021/5802110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 11/23/2021] [Accepted: 11/29/2021] [Indexed: 11/17/2022]
Abstract
Background The advance of new treatment strategies for more effective management of oral cancer requires identification of novel biological targets. Therefore, the purpose of this study is to identify novel biomarkers associated with oral tumorigenesis and prognostic signature by comparing gene expression profile of oral squamous cell carcinomas (OSCCs). Methods Four datasets including GSE25099, GSE30784, GSE37991, and GSE41613 were collected from Gene Expression Omnibus (GEO) database. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, Cox model analysis, identification of key genes, and Kaplan-Meier analysis were also performed. The xCell was utilized to analyze the infiltration levels of immune cells. Results A total of 235 differentially expressed genes (DEGs) were found to be dysregulated in OSCC. These genes were mainly enriched in ECM receptor interaction and focal adhesion. Cox regression analysis identified 10 genes considered as key genes. Kaplan-Meier analysis showed that low expression of SERPINE1 (also known as PAI-1), high expression of CD1C, and C-X3-C motif chemokine receptor 1 (CX3CR1) were associated with well prognostic status in OSCC patients. In addition, we constructed a 3-immune-cell signature (myeloid dendritic cell, T cell CD4+ central memory, and common myeloid progenitor) that may be used to predict the survival status of OSCC patients. Conclusion Three key genes and 3-immune-cell signature were potential biomarkers for the prognosis of OSCC, and they may serve as potential targets for the treatment of OSCC patients.
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Nigam K, Srivastav RK. Notch signaling in oral pre-cancer and oral cancer. Med Oncol 2021; 38:139. [PMID: 34633549 DOI: 10.1007/s12032-021-01593-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 09/29/2021] [Indexed: 10/20/2022]
Abstract
Notch signaling involves cell to cell contact. It is an ancient signaling mechanism that is conserved throughout the animal kingdom. The basic function of Notch signaling is to decide cell fate and execute asymmetrical division. Notch signaling is indispensable for embryo growth. Aberrant Notch signaling involves in cancer progression by altering cell proliferation rate, tumor micro-environment, stem cell activities. The role of Notch signaling in cancer progression is context-dependent. In breast cancer and T cell lymphoma Notch signaling is highly active, whereas in squamous cell carcinoma (SCC) as oral and skin cancer, the signaling is suppressed. It is believed that in SCC, Notch-mediated tumor growth is due to the cell non-autonomous function. Oral cancer is the 6th most risky cancer worldwide. In many patients, oral cancer is preceded by pre-cancer conditions. In this review, we have summarized the research knowledge related to the role of Notch signaling in oral cancer and pre-cancer conditions and the therapeutic options available targeting different components of Notch pathways.
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Affiliation(s)
- Kumud Nigam
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow Campus, Lucknow, 226028, Uttar Pradesh, India
| | - Ratnesh Kumar Srivastav
- Department of Oral Pathology & Microbiology, King George's Medical University, Lucknow, Uttar Pradesh, 226003, India.
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Cai JL, Zhu GQ, Du JX, Wang B, Wan JL, Xiao K, Dai Z. Identification and validation of a new gene signature predicting prognosis of hepatocellular carcinoma patients by network analysis of stemness indices. Expert Rev Gastroenterol Hepatol 2021; 15:699-709. [PMID: 33131341 DOI: 10.1080/17474124.2021.1845142] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Background: Stem cells play an important role in hepatocellular carcinoma (HCC). However, their precise effect on HCC tumorigenesis and progression remains unclear. The present study aimed to characterize stem cell-related gene expression in HCC.Methods: The mRNA expression-based stemness index (mRNAsi) was used to analyze the clinical characteristics and prognosis of HCC patients. The weighted gene co-expression network analysis (WGCNA) was used to construct a gene co-expression network of 374 HCC patients. Finally, six genes were used to construct the prognosis signature.Results: HCC patients had a higher mRNAsi score than healthy people, suggesting poor prognosis. Two gene modules highly related to mRNAsi were identified. Multivariate Cox analysis was carried out to establish a Cox proportional risk regression model. The risk score for each patient was the sum of the product of each gene expression and its coefficient. Survival analysis suggested that the low-risk group had a significantly better prognosis.Conclusions: The established six-gene signature was able to predict patient prognosis accurately. This new signature should be verified in prospective studies in order to determine patient prognosis in clinical decision-making.
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Affiliation(s)
- Jia-Liang Cai
- Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai, China
| | - Gui-Qi Zhu
- Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai, China
| | - Jun-Xian Du
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Biao Wang
- Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai, China
| | - Jing-Lei Wan
- Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai, China
| | - Kun Xiao
- Department of Liver Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhi Dai
- Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai, China
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Qu H, Zhao H, Zhang X, Liu Y, Li F, Sun L, Song Z. Integrated Analysis of the ETS Family in Melanoma Reveals a Regulatory Role of ETV7 in the Immune Microenvironment. Front Immunol 2020; 11:612784. [PMID: 33424867 PMCID: PMC7786291 DOI: 10.3389/fimmu.2020.612784] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 11/19/2020] [Indexed: 12/22/2022] Open
Abstract
The ETS family modulates immune response and drug efficiency to targeted therapies, but their role in melanoma is largely unclear. In this study, the ETS family was systematically analyzed in multiple public data sets. Bioinformatics tools were used to characterize the function of ETV7 in melanoma. A prognostic model was constructed using the LASSO Cox regression method. We found that ETV7 was the only differentially expressed gene with significant prognostic relevance in melanoma. Enrichment analysis of seven independent data sets indicated ETV7 participation in various immune-related pathways. ETV7 particularly showed a strong positive correlation with CD8+ T cell infiltration. The prognostic model based on ETV7 and its hub genes showed a relatively good predictive value in training and testing data sets. Thus, ETV7 can potentially regulate the immune microenvironment in melanoma.
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Affiliation(s)
- Hui Qu
- Department of Plastic Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, China
| | - Hui Zhao
- Department of Urology, The Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Xi Zhang
- Department of Oncology, The Third Xiangya Hospital of Central South University, Changsha, China
| | - Yang Liu
- Department of Pathology, The Third Xiangya Hospital of Central South University, Changsha, China
| | - Feng Li
- Department of Plastic Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, China
| | - Liyan Sun
- Department of Plastic Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, China
| | - Zewen Song
- Department of Oncology, The Third Xiangya Hospital of Central South University, Changsha, China
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