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

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.

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Clinical Significance of the Decreased Expression of hsa_circ_001242 in Oral Squamous Cell Carcinoma

Disease Markers ◽

10.1155/2018/6514795 ◽

2018 ◽

Vol 2018 ◽

pp. 1-6 ◽

Cited By ~ 13

Author(s):

Shuai Sun ◽

Bowen Li ◽

Yufan Wang ◽

Xiang Li ◽

Panpan Wang ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Cell Lines ◽

Squamous Cell ◽

Roc Curve ◽

Human Cancer ◽

Circular Rnas ◽

Limited Information ◽

Expression Levels

Background. Circular RNAs (circRNAs) are a type of covalently closed loop structure of endogenous RNAs. Recent studies have shown that circular RNAs may play an important role in human cancer. However, there is limited information on the function of circRNA in oral squamous cell carcinoma (OSCC). Methods. Hsa_circ_001242 expression levels in 40 paired OSCC tissues and four OSCC cell lines were selected using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of hsa_circ_001242 in OSCC. Results. Hsa_circ_001242 was significantly downregulated in OSCC tissues compared to paired adjacent normal tissues (P<0.001). Hsa_circ_001242 expression levels were significantly downregulated in four OSCC cell lines (SCC-9, SCC-15, SCC25, and CAL-27) than in human normal oral keratinocyte (HOK) cell lines. Moreover, the expression level of hsa_circ_001242 was negatively correlated with tumor size and T stage (P<0.05). The area under the ROC curve was 0.784. Conclusion. This study showed that hsa_circ_001242 was significantly downregulated in OSCC and may act as a potential novel biomarker for the diagnosis and treatment of OSCC.

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Hsa_circ_0003829 serves as a potential diagnostic predictor for oral squamous cell carcinoma

Journal of International Medical Research ◽

10.1177/0300060520936880 ◽

2020 ◽

Vol 48 (9) ◽

pp. 030006052093688

Author(s):

Hanyu Zhang ◽

Yuehong Shen ◽

Biru Zhang ◽

Min Qian ◽

Ying Zhang ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Roc Curve ◽

Quantitative Polymerase Chain Reaction ◽

Clinical Samples ◽

Circular Rnas ◽

Prospective Clinical Study ◽

Aberrant Expression

Objective Increasing evidence suggests that circular RNAs (circRNAs) play a major role in tumorigenesis and cancer progression. This study aimed to identify aberrant expression of hsa_circ_0003829 in oral squamous cell carcinoma (OSCC) and to explore its clinical significance. Methods We conducted a prospective clinical study to examine the expression pattern of hsa_circ_0003829 in 60 paired OSCC and normal clinical samples and in cell lines using real-time quantitative polymerase chain reaction. We also evaluated the diagnostic value of hsa_circ_0003829 in OSCC based on receiver operating characteristic (ROC) curve analysis, and examined the relationships between hsa_circ_0003829 expression and clinicopathological features in patients with OSCC. We further used bioinformatics software CircInteractome ( https: //Circinteractome.nia.nih.gov/ ) to predict circRNA–microRNA interactions. Results Hsa_circ_0003829 was significantly downregulated in OSCC compared with adjacent normal tissues. The area under the ROC curve was 0.81. Low expression levels of hsa_circ_0003829 in OSCC tissues were negatively correlated with lymph node metastasis status and TNM stage. Conclusions Downregulated expression of has_circ_0003829 suggests that this may be a key circRNA in OSCC, and may serve as a prospective biomarker for the diagnosis of OSCC.

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The integration of differentially expressed genes based on multiple microarray datasets for prediction of the prognosis in oral squamous cell carcinoma

Bioengineered ◽

10.1080/21655979.2021.1947076 ◽

2021 ◽

Vol 12 (1) ◽

pp. 3309-3321

Author(s):

Yinuan Zhao ◽

Jiacheng Huang ◽

Jianzhi Chen

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Differentially Expressed Genes ◽

Squamous Cell ◽

Differentially Expressed ◽

Microarray Datasets

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Transcriptome analysis reveals differentially expressed lncRNAs between oral squamous cell carcinoma and healthy oral mucosa

Oncotarget ◽

10.18632/oncotarget.16358 ◽

2017 ◽

Vol 8 (19) ◽

pp. 31521-31531 ◽

Cited By ~ 43

Author(s):

Lu Feng ◽

John R. Houck ◽

Pawadee Lohavanichbutr ◽

Chu Chen

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Oral Mucosa ◽

Squamous Cell ◽

Transcriptome Analysis ◽

Differentially Expressed

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Saliva protein biomarkers to detect oral squamous cell carcinoma in a high-risk population in Taiwan

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1612368113 ◽

2016 ◽

Vol 113 (41) ◽

pp. 11549-11554 ◽

Cited By ~ 43

Author(s):

Jau-Song Yu ◽

Yi-Ting Chen ◽

Wei-Fan Chiang ◽

Yung-Chin Hsiao ◽

Lichieh Julie Chu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

High Risk ◽

Oral Cancer ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Risk Score ◽

Squamous Cell ◽

Low Risk ◽

Healthy Controls ◽

Protein Biomarkers

Most cases of oral squamous cell carcinoma (OSCC) develop from visible oral potentially malignant disorders (OPMDs). The latter exhibit heterogeneous subtypes with different transformation potentials, complicating the early detection of OSCC during routine visual oral cancer screenings. To develop clinically applicable biomarkers, we collected saliva samples from 96 healthy controls, 103 low-risk OPMDs, 130 high-risk OPMDs, and 131 OSCC subjects. These individuals were enrolled in Taiwan’s Oral Cancer Screening Program. We identified 302 protein biomarkers reported in the literature and/or through in-house studies and prioritized 49 proteins for quantification in the saliva samples using multiple reaction monitoring-MS. Twenty-eight proteins were successfully quantified with high confidence. The quantification data from non-OSCC subjects (healthy controls + low-risk OPMDs) and OSCC subjects in the training set were subjected to classification and regression tree analyses, through which we generated a four-protein panel consisting of MMP1, KNG1, ANXA2, and HSPA5. A risk-score scheme was established, and the panel showed high sensitivity (87.5%) and specificity (80.5%) in the test set to distinguish OSCC samples from non-OSCC samples. The risk score >0.4 detected 84% (42/50) of the stage I OSCCs and a significant portion (42%) of the high-risk OPMDs. Moreover, among 88 high-risk OPMD patients with available follow-up results, 18 developed OSCC within 5 y; of them, 77.8% (14/18) had risk scores >0.4. Our four-protein panel may therefore offer a clinically effective tool for detecting OSCC and monitoring high-risk OPMDs through a readily available biofluid.

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SCCA, TSGF, and the Long Non-Coding RNA AC007271.3 are Effective Biomarkers for Diagnosing Oral Squamous Cell Carcinoma

Cellular Physiology and Biochemistry ◽

10.1159/000489741 ◽

2018 ◽

Vol 47 (1) ◽

pp. 26-38 ◽

Cited By ~ 15

Author(s):

Tingru Shao ◽

Jiaxin Huang ◽

Zenan Zheng ◽

Qingqing Wu ◽

Tiancai Liu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Case Control Study ◽

Case Control ◽

Differentially Expressed ◽

Normal Controls ◽

Control Study ◽

Potential Biomarkers

Background/Aims: Oral squamous cell carcinoma (OSCC) is one of the most lethal malignancies worldwide and the most common type of oral cancer, characterized by invasive growth, frequent regional metastases, high recurrence, and poor prognosis. In the current study, we investigated the use of long non-coding RNAs (lncRNAs), tumor-specific growth factor (TSGF), and squamous cell carcinoma antigen (SCCA) as potential biomarkers for OSCC screening. Methods: LncRNA expression was measured by microarray analysis in three sets of OSCC and paired normal mucosal tissues. The potential lncRNAs involved in OSCC development were investigated by bioinformatics and verification experiments. We also determined the expression of these potential biomarkers in tissue and serum samples in a case–control study of 80 OSCC cases and 70 controls. Receiver operating characteristics, decision curve analysis, and the combined detection of lncRNA AC007271.3, TSGF, and SCCA were carried out to screen for OSCC biomarkers. Results: A total of 691 lncRNAs (433 upregulated and 258 downregulated) were differentially expressed in OSCC tissues compared with normal controls (p< 0.05). Based on Gene Ontology and pathway analysis, we selected four differentially expressed lncRNAs (AC007271.3, AC007182.6, LOC283481, and RP11-893F2.9), and showed that aberrant AC007271.3 levels in OSCC patients were significantly associated with clinical stage, especially in early-stage disease, in an expanded case–control study. The combination of AC007271.3 and SCCA (AUC=0.902, p< 0.001) showed significantly better ability to discriminate between OSCC and controls compared with SCCA or AC007271.3 alone. Serum AC007271.3, SCCA, and TSGF levels could also discriminate between OSCC and normal controls with sensitivities of 77.6%, 55.0%, and 63.3%, and specificities of 84.5%, 93.3%, and 66.7%, respectively. Conclusions: These results suggest that AC007271.3, SCCA, and TSGF could be novel circulating biomarkers for the determination of OSCC. However, further validation in large-scale prospective studies is necessary.

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