Salivary Circular RNAs Hsa_Circ_0001874 and Hsa_Circ_0001971 as Novel Biomarkers for the Diagnosis of Oral Squamous Cell Carcinoma

Abstract

Background/Aims: Recent studies have demonstrated that circular RNAs (circRNAs) can serve as potential molecular markers for disease diagnosis. However, little is known about their diagnostic potential for oral squamous cell carcinoma (OSCC). This study aimed to determine the expression of circRNAs in the saliva of OSCC patients to identify novel biomarkers for OSCC screening. Methods: Microarray screening of circRNA was performed to identify differentially expressed circRNAs in saliva from 3 OSCC patients compared with 3 healthy controls. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the results, and the association between these confirmed salivary circRNAs and clinicopathological features was analyzed using the chi-squared test. A receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic value of the circRNAs identified. Preoperative expression and postoperative expression (1 month after the surgery) of hsa_circ_0001874 and hsa_circ_0001971 was also determined. Results: Our results indicated 12 upregulated and 20 downregulated circRNAs in the saliva from the OSCC patients compared with that from the healthy controls. Among the differentially expressed circRNAs, hsa_circ_0001874, hsa_circ_0001971, and hsa_circ_0008068 were upregulated and hsa_circ_0000140, hsa_circ_0002632, and hsa_circ_0008792 were downregulated in the OSCC group versus the healthy group. Clinical data indicated that salivary hsa_circ_0001874 was correlated with TNM stage (P=0.006) and tumor grade (P=0.023) and that hsa_circ_0001971 was correlated with TNM stage (P=0.019). The combination of hsa_circ_0001874 and hsa_circ_0001971 showed an area under the ROC curve of 0.922 (95% confidence interval, 0.883-0.961; P< 0.001). The risk score based on the combination of hsa_circ_0001874 and hsa_circ_0001971 also discriminated patients with OSCC from patients with oral leukoplakia (P< 0.001). Moreover, the expression levels of salivary hsa_circ_0001874 and hsa_circ_0001971 were clearly decreased in the postoperative samples compared with preoperative samples (P< 0.001). Conclusions: This is the first study to demonstrate the potential of salivary hsa_circ_0001874 and hsa_circ_0001971 as biomarkers for the diagnosis of OSCC.

hsa_circRNA_100533 regulates GNAS by sponging hsa_miR_933 to prevent oral squamous cell carcinoma

“…It was reported that hsa_circ_0008309 and hsa_circ_001242 was significantly downregulated in OSCC tissues, correlated with pathological differentiation of OSCC, and may act as a potential novel biomarker for the diagnosis and treatment of OSCC . In addition, salivary hsa_circ_0001874 and hsa_circ_0001971 also act as biomarkers for diagnosing OSCC . In our study, hsa_circRNA_100533 was significantly downregulated in tissues of patients with OSCC, which suggested that hsa_circRNA_100533 might be a potential diagnostic marker for OSCC.…”

“…11,22 In addition, salivary hsa_circ_0001874 and hsa_circ_0001971 also act as biomarkers for diagnosing OSCC. 23 In our study, hsa_circRNA_100533 was significantly downregulated in tissues of patients with OSCC, which suggested that hsa_circRNA_100533 might be a potential diagnostic marker for OSCC. Furthermore, we also evaluated the expression and biological functions of hsa_circRNA_100533 in OSCC cell lines.…”

circRNA_0000140 suppresses oral squamous cell carcinoma growth and metastasis by targeting miR-31 to inhibit Hippo signaling pathway

“…circRNA_100290, on the other hand, functions as a competing endogenous RNA (ceRNA), which regulates other RNA transcripts by competing for shared microRNAs (miRNAs), to antagonize miR-378a-driven GLUT1 suppression, finally leading to the induction of glycolysis and cell proliferation in OSCC 18 . While significant lower expression of circ_0000140 was found in OSCC patients 19 , the molecular mechanism behind this is still unclear.…”

<p>Circular RNA circHUWE1 Is Upregulated and Promotes Cell Proliferation, Migration and Invasion in Colorectal Cancer by Sponging miR-486</p>

“…Increasing studies have reported that circRNAs have the potential to serve as biomarkers to detect cancer. [18][19][20] We used the ROC curve to assess the diagnostic value of circHUWE1 for CRC. The AUC was 0.732 ( Figure 2D), which showed that circHUWE1 may serve as a potential diagnostic biomarker for CRC.…”