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Patel A, Patel S, Patel P, Mandlik D, Patel K, Tanavde V. Salivary Exosomal miRNA-1307-5p Predicts Disease Aggressiveness and Poor Prognosis in Oral Squamous Cell Carcinoma Patients. Int J Mol Sci 2022; 23:ijms231810639. [PMID: 36142544 PMCID: PMC9505291 DOI: 10.3390/ijms231810639] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 09/07/2022] [Accepted: 09/09/2022] [Indexed: 11/16/2022] Open
Abstract
Background: Salivary exosomal miRNAs as biomarkers facilitate repeated sampling, real-time disease monitoring and assessment of therapeutic response. This study identifies a single salivary exosomal miRNA prognosticator that will aid in improved patient outcome using a liquid biopsy approach. Method: Small RNA and transcriptome sequencing profiles of tumour tissues (n = 12) and salivary exosomes (n = 8) from oral cancer patients were compared to their non-cancerous counterparts. We validated these results using The Cancer Genome Atlas database and performing Real-time PCR on a large patient cohort (n = 19 tissue samples; n = 12 salivary exosomes). Potential target genes and the miRNA–mRNA networks and enriched biological pathways regulated by this microRNA were identified using computational tools. Results: Salivary exosomes (size: 30–50 nm) demonstrated a strong expression of CD47 and detectable expression of tetraspanins CD63, CD81 and CD9 by flow cytometry. miR-1307-5p was exclusively overexpressed in tissues and salivary exosomes of oral cancer patients compared to their non-cancerous counterparts. Enhanced expression of miR-1307-5p clinically correlated with poor patient survival, disease progression, aggressiveness and chemo-resistance. Transcriptome analysis suggested that miRNA-1307-5p could promote oral cancer progression by suppressing THOP1, EHF, RNF4, GET4 and RNF114. Conclusions: Salivary exosomal miRNA-1307-5p is a potential prognosticator for predicting poor survival and poor patient outcome in oral cancers.
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Affiliation(s)
- Aditi Patel
- Biological and Life Sciences, School of Arts and Sciences, Ahmedabad University, Ahmedabad 380009, India
| | - Shanaya Patel
- Biological and Life Sciences, School of Arts and Sciences, Ahmedabad University, Ahmedabad 380009, India
| | - Parina Patel
- Biological and Life Sciences, School of Arts and Sciences, Ahmedabad University, Ahmedabad 380009, India
| | - Dushyant Mandlik
- Department of Head and Neck Oncology, HCG Cancer Centre, Ahmedabad 380060, India
| | - Kaustubh Patel
- Department of Head and Neck Oncology, HCG Cancer Centre, Ahmedabad 380060, India
| | - Vivek Tanavde
- Biological and Life Sciences, School of Arts and Sciences, Ahmedabad University, Ahmedabad 380009, India
- Bioinformatics Institute, Agency for Science Technology and Research (A*STAR), Singapore 138671, Singapore
- Correspondence:
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Hurník P, Chyra Z, Ševčíková T, Štembírek J, Trtková KS, Gaykalova DA, Buchtová M, Hrubá E. Epigenetic Regulations of Perineural Invasion in Head and Neck Squamous Cell Carcinoma. Front Genet 2022; 13:848557. [PMID: 35571032 PMCID: PMC9091179 DOI: 10.3389/fgene.2022.848557] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Accepted: 03/09/2022] [Indexed: 11/13/2022] Open
Abstract
Carcinomas of the oral cavity and oropharynx belong among the ten most common malignancies in the human population. The prognosis of head and neck squamous cell carcinoma (HNSCC) is determined by the degree of invasiveness of the primary tumor and by the extent of metastatic spread into regional and distant lymph nodes. Moreover, the level of the perineural invasion itself associates with tumor localization, invasion's extent, and the presence of nodal metastases. Here, we summarize the current knowledge about different aspects of epigenetic changes, which can be associated with HNSCC while focusing on perineural invasion (PNI). We review epigenetic modifications of the genes involved in the PNI process in HNSCC from the omics perspective and specific epigenetic modifications in OSCC or other neurotropic cancers associated with perineural invasion. Moreover, we summarize DNA methylation status of tumor-suppressor genes, methylation and demethylation enzymes and histone post-translational modifications associated with PNI. The influence of other epigenetic factors on the HNSCC incidence and perineural invasion such as tobacco, alcohol and oral microbiome is overviewed and HPV infection is discussed as an epigenetic factor associated with OSCC and related perineural invasion. Understanding epigenetic regulations of axon growth that lead to tumorous spread or uncovering the molecular control of axon interaction with cancer tissue can help to discover new therapeutic targets for these tumors.
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Affiliation(s)
- Pavel Hurník
- Department of Clinical and Molecular Pathology and Medical Genetics, Faculty of Medicine and University Hospital Ostrava, Ostrava, Czechia
- Department of Histology and Embryology, Medical Faculty, Masaryk University, Brno, Czechia
| | - Zuzana Chyra
- Department of Hematooncology, University Hospital Ostrava, Ostrava, Czechia
| | - Tereza Ševčíková
- Department of Hematooncology, University Hospital Ostrava, Ostrava, Czechia
| | - Jan Štembírek
- Department of Maxillofacial Surgery, University Hospital Ostrava, Ostrava, Czechia
- Laboratory of Molecular Morphogenesis, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Brno, Czechia
| | - Kateřina Smešný Trtková
- Department of Clinical and Molecular Pathology and Medical Genetics, Faculty of Medicine and University Hospital Ostrava, Ostrava, Czechia
- Department of Clinical and Molecular Pathology, Faculty of Medicine and University Hospital Olomouc, Olomouc, Czechia
| | - Daria A. Gaykalova
- Department of Otorhinolaryngology-Head and Neck Surgery, University of Maryland Medical Center, Baltimore, MD, United States
- Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland Medical Center, Baltimore, MD, United States
- Institute for Genome Sciences, University of Maryland Medical Center, Baltimore, MD, United States
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, United States
| | - Marcela Buchtová
- Laboratory of Molecular Morphogenesis, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Brno, Czechia
- Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czechia
| | - Eva Hrubá
- Laboratory of Molecular Morphogenesis, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Brno, Czechia
- Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czechia
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