Circulating microRNA Panel as a Potential Novel Biomarker for Oral Squamous Cell Carcinoma Diagnosis

Abstract

A lack of reliable biomarkers for oral squamous cell carcinoma (OSCC) poses a major clinical issue. The sensitivity and specificity of classical serum tumor markers, such as the squamous cell carcinoma antigen (SCC-Ag), are quite poor, especially for early detection. This study aimed to identify specific serum miRNAs potentially serving as OSCC biomarkers. The expression levels of candidate miRNAs in serum samples from 40 OSCC patients and 40 healthy controls were quantitatively analyzed via microarray and reverse transcription PCR (RT-PCR) analyses. To enhance the accuracy of detection, we used Fisher’s linear discriminant analysis to establish a diagnostic model that incorporated a combination of selected miRNAs. Consequently, miR-19a and miR-20a were significantly upregulated in the patient group (p = 0.014 and 0.036, respectively), whereas miR-5100 was downregulated (p = 0.001). We found that a combination of six miRNAs (miR-24, miR-20a, miR-122, miR-150, miR-4419a, and miR-5100) could distinguish between OSCC and the control group with a higher degree of accuracy (Area Under the Curve, AUC: 0.844, sensitivity: 55%, and specificity: 92.5%). Furthermore, compared to serum SCC antigen, the 6-miRNA panel could accurately detect the presence of OSCC. The present specific miRNAs panel may serve as a novel candidate biomarker of oral cancer.

Simultaneous Recognition of Over- and Under-Expressed MicroRNAs Using Nanopore Decoding

“…Employing the asymmetric electrolyte conditions, three types of output duplex-detection signals were observed even when using clinical samples (Figure S12). The signals could be classified based on the reference data; however, the experimentally obtained abundance ratio of the output duplexes conflicted with the miRNA profiling trends in the previous report; 29 our data indicated under-expression of both miR-19a and miR-5100 in OSCC patients (Figure S12).…”

“…According to the quantitative analysis, the over-(miR-19a) and under-(miR-5100) expression level was determined to be 2-and 0.5-fold, respectively. 29 simultaneous pattern recognition of these miRNAs, we here utilized sequence design for DNA-based parallel computation 1,20 and designed dgDNAs, which consisted of a partially complementary sequence with target miRNAs (Figure 1b). As a proof of concept, four expression patterns of target miRNAs were prepared involving over/under-expression, and we thermodynamically simulated the molecular computation using nanomolar concentrations of oligonucleotides (described in detail in the Experimental Section).…”

“…Our targeting miR-19a and miR-5100 have been reported to be 2fold over-expressed and 0.5-fold under-expressed, respectively, in the serum of human OSCC patients. 29 Since the collected serum samples from OSCC patients (N = 3) and healthy volunteers (N = 3) had the same clinicopathological background as in the previous report, 29 we first attempted nanopore measurement using pooled samples containing miRNAs extracted from the serum samples. Employing the asymmetric electrolyte conditions, three types of output duplex-detection signals were observed even when using clinical samples (Figure S12).…”

The clinical implications of circulating microRNAs as potential biomarkers in screening oral squamous cell carcinoma

“…The influence analysis and outlier detection identified several outlier individual studies. After excluding seven outliers ( 34 , 38 , 41 , 47 , 48 ), the I 2 for heterogeneity decreased both in sensitivity (from 91.49% to 84.30%) and specificity (from 89.17% to 84.31%). However, the overall results showed only minimal changes and were similar to the original ones as the pooled specificity of the overall study increased from 0.76 to 0.78, PLR increased from 3.2 to 3.4, DOR decreased from 9 to 10, and AUC increased from 0.82 to 0.83, while sensitivity and NLR had no changes.…”

Liquid Biopsy for Oral Cancer Diagnosis: Recent Advances and Challenges

“…The model could identify 13 cancer types with high accuracy. Regarding the early detection of oral cancer, Nakamura et al found that serum miRNA expression signatures, including miR-19a, miR-20a, and miR-5100, could distinguish between OSCC patients and healthy donors with high diagnostic accuracy [ 20 ]. Romani et al conducted a microarray analysis of salivary miRNAs and identified 25 miRNAs expressed differently between OSCC patients and healthy controls [ 21 ].…”