Salivary miR-31-5p, miR-345-3p, and miR-424-3p Are Reliable Biomarkers in Patients with Oral Squamous Cell Carcinoma.

Beáta Scholtz,Csongor Kiss,Ildikó Tar,Ildikó J Márton,József Horváth

doi:10.3390/pathogens11020229

Beáta Scholtz, Csongor Kiss + Show 3 more

Open Access

https://doi.org/10.3390/pathogens11020229

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Journal: Pathogens	Publication Date: Feb 9, 2022
Citations: 13	License type: CC BY 4.0

Affiliation: University of Debrecen

Abstract

If not detected early, oral squamous cell carcinoma (OSCC) has very poor prognosis, emphasizing the need for reliable early diagnostics. Saliva is considered a promising surrogate biosample for OSCC detection, because it comes into contact with many cells of the tumor mass, providing a comprehensive sampling of tumor-specific biomolecules. Although several protein- and RNA-based salivary biomarkers have been proposed for the detection of OSCC, the results of the studies show large differences. Our goal was to clarify which salivary microRNAs (miRNA) show reliably high expression in the saliva of OSCC patients, to be used as cancer-specific biomarkers, and potentially as early diagnostic biomarkers. Based on a detailed literature search, we selected six miRNAs commonly overexpressed in OSCC, and analyzed their expression in saliva samples of cancer patients and controls by real-time quantitative PCR. Our results suggest that miR-345 and miR-31-5p are consistently upregulated salivary biomarkers for OSCC, and a three-miRNA panel of miR-345, miR-31-5p, and miR-424-3p can distinguish cancer and control patients with high sensitivity.

Highlights

Saliva has long been considered a prime candidate for oral squamous cell carcinoma (OSCC) liquid biopsy, because it rinses continuously the oral cavity, effectively sampling the entire surface of the oral mucosa [1,2]
The miRNA expression profile specific to OSCC has been studied in detail, but different studies have identified rather different up- or downregulated miRNA sets, possibly due to the well-known heterogeneity of OSCC tumors, maybe due to varied experimental approaches as well. miRNAs overexpressed by the OSCC tumor mass might be suitable salivary biomarkers [10], but there are several complications
From the resulting list of publications (782), we selected 9 studies that conformed to the following criteria: (1) the initial phase of the studies analyzed more than 20 primary OSCC samples, or saliva of OSCC patients; (2) the initial phase of the studies used a global profiling approach, targeting a large number of miRNAs; and (3) after microarray or next-generation sequencing profiling, the results were validated by quantitative PCR (qPCR) in phase II (Table 1, global screening studies, and Supplementary Table)

Summary

Introduction

Saliva has long been considered a prime candidate for OSCC liquid biopsy, because it rinses continuously the oral cavity, effectively sampling the entire surface of the oral mucosa [1,2]. MiRNAs are selectively released by tumor cells via extracellular vesicles [11,12], and second, saliva is a surrogate sample, containing EVs released by many other normal cells [13,14]. All this variability has translated into the identification of different miRNA-based OSCC biomarker panels, with little overlap between the studies. These miRNAs all have altered expression in OSCC, in oral precancerous states, or in the saliva of these patients (inclusion criteria), but have no known involvement in oral inflammatory diseases (an exclusion criterion)

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