Salivary exosomal microRNAs as biomarkers for head and neck cancer detection—a literature review

Abstract

Background MicroRNAs (miRs) are small, non-coding mRNA molecules which regulate cellular processes in tumorigenesis. miRs were discovered in extracellular environment and biological fluids, carrying marks of head and neck squamous cell carcinoma (HNSCC). They were also identified in abundance in salivary exosomes, in which they are protected by exosome lipid barrier against enzymatic injuries and therefore, the accuracy of exosomal miR-based cancer detection increase. This systematic review aimed to reveal and inventorize the most reliable exosomal miRNAs in saliva samples which can be used as novel biomarkers for early detection of HNSCC. Materials and methods A systematic literature search, according to PRISMA guideline, was performed on Pubmed and Google Academic libraries, based on specific keywords. Original articles published between 2010 and 2021 were selected. The quality of each paper was assessed using the Quality Evaluation Scoring Tool. Results At the end of selection process, five studies met the inclusion criteria. These studies analyzed twelve salivary exosomal miRs, presenting different methods of exosome and miR identification for HNSCC detection. A comprehensive explanation of the miR pathways of action was drawn and illustrated in this review. Conclusion Exosomal miRs are promising biomarkers for oral cavity and oropharyngeal cancer detection. miR-10b-5p, miR-486-5p, miR-24-3p and miR-200a stand as the most useful ones in saliva sample examination.

Role of Salivary MicroRNA and Cytokines in the Diagnosis and Prognosis of Oral Squamous Cell Carcinoma

“…Notably, the expression of miRNA-34 was greater in high-grade OSCCs, and the expression of miRNA-486-5p assisted the detection of stage I OSCC, demonstrating the potential usefulness of salivary exosomal miRNAs for the early diagnosis of cancer [10]. In the same way, it has been found that miRNAs-4484 and 10b-5p are biomarkers of the malignant transformation of oral lichen planus and oral dysplasia in OSCC [8,10,11], and a lower expression of miRNA-200a has been associated with a higher risk of malignant transformation and oral cancer. Finally, miR-365 has been found to regulate transcription, promoting oncogenesis and metastasis in some cancers but suppressing these processes in others [12].…”

“…In this way, miRNAs with oncogenic function are upregulated and responsible for silencing tumor-suppressor genes that can modulate the onset, development, and metastasis of cancer cells. Conversely, miRNAs with tumor-suppressor function are downregulated, reducing the modulation of oncogenes and maintaining malignity [8].…”

“…One advantage of salivary exosomal miRNA over other OSCC biomarkers is that it can be detected in small amounts of saliva and by analysis of the whole saliva sample or the supernatant. The following salivary exosomal miRNAs have been correlated with disease stage, histopathological type and/or grade: miRNA-24-3P, 412-3p, 512-3p, 302b-3p, 517b-3p, 134, 486-5p, 4484, 10b-5p, 200a, and 365 [8][9][10][11]31,32]. Notably, the expression of miRNA-34 was greater in high-grade OSCCs, and the expression of miRNA-486-5p assisted the detection of stage I OSCC, demonstrating the potential usefulness of salivary exosomal miRNAs for the early diagnosis of cancer [10].…”

The Promise of Circulating Tumor DNA in Head and Neck Cancer

“…Various other metabolites and biomarkers have been shown to concentrate within EXOs and show additional promise in the identification and monitoring of HNC. Within the blood and saliva of HNSCC patients, microRNAs (miRNA)—or small, non-coding mRNA molecules—have been noted to mediate various cellular processes in tumorigenesis [ 121 ]. Various investigators have demonstrated the role of miRNA and salivary-derived EXOs as novel HNSCC biomarkers [ 122 , 123 , 124 , 125 ].…”

MicroRNAs: Their Role in Metabolism, Tumor Microenvironment, and Therapeutic Implications in Head and Neck Squamous Cell Carcinoma

“…The ROC curves obtained, which showed obvious discrimination between normal and cancer patients (AUC = 0.864 and 0.960 for miR-196a and miR-196b, respectively) suggested that these miRNAs are specific circulating miRNA biomarkers for oral cancer patients when compared with the healthy controls. Otherwise, exosomal miRNAs can be identified in the TME and can circulate freely in body fluids, which also makes them suitable for acting as non-invasive biomarkers in clinical applications [116][117][118]. Utilizing a new generation of miRNA sequencing technology, Langevin et al demonstrated that exosomal miR-486-5p, miR-486-3p, and miR-10b-5p were detectable in saliva for a set of HNSCC patients, and these might be exploited as noninvasive salivary biomarkers [119].…”