Circular RNAs are Potential Prognostic Markers of Head and Neck Squamous Cell Carcinoma: Findings of a Meta-Analysis Study

Abstract

BackgroundSeveral studies have reported the role of circRNAs in the pathogenesis, diagnosis and prognosis of different cancers. This meta-analysis study aimed to evaluate the potential of using circRNAs as prognostic biomarkers of head and neck squamous cell carcinoma (HNSCC).Methods816 relevant articles were retrieved from PubMed and Science Direct databases, out of which 17 met the inclusion criteria. These 17 studies were assessed for quality by the Newcastle-Ottawa Scale (NOS) system, and 9 high quality studies (NOS>7) were included in the meta-analysis. Cochran Q test and the I square (I2) metric were calculated to detect potential heterogeneity among studies. Sensitivity analysis was performed to validate the credibility of outcomes, and publication bias was determined using Begg’s funnel plot and Egger’s test. Hazard ratio (HR) and 95% Confidence Intervals (CIs) were used to evaluate overall survival (OS) of HNSCC patients by univariate and multivariate analyses.ResultsThe dysregulated levels of 9 circRNAs (circPVT1, circCORO1C, circ_0000199, circCUX1, circPARD3, circMYC, circ_0102272, circ_0092125 and circ_00072387) were inversely related to OS of HNSCC patients [upregulated circRNA (univariate analysis: HR = 3.40, 95% CI: 2.66-4.36, p < 0.0001, I2 = 0%; multivariate analysis: HR = 3.33, 95% CI: 2.54-4.38, p < 0.0001, I2 = 0%), downregulated circRNA (univariate analysis: HR = 2.83, 95% CI: 1.73-4.65, p < 0.0001, I2 = 57.8%; multivariate analysis: HR = 2.35, 95% CI: 1.42-3.89, p = 0.0009, I2 = 0%)]. The individual HR for these 9 circRNAs indicated inverse relation to OS, validating the overall HR. The dyregulated levels of these circRNAs were also associated with poor clinicopathological outcomes such as primary tumor size, lymph node metastasis, distant metastasis and poor tumor (T), nodes (N), metastases (M); i.e TNM staging, and six of these circRNAs regulated diverse micro RNAs, revealing their role in tumorigenesis and cancer progression.ConclusionNine different circRNAs dysregulated in HNSCC tumors may serve as potential prognostic markers of HNSCC. These markers are associated with reduced OS and poor clinicopathological outcomes of HNSCC patients. They are also involved in the pathogenesis and progression of HNSCC through diverse mechanisms.

RNA-Based Liquid Biopsy in Head and Neck Cancer

“…The wide availability and diversity of tissuespecific circRNAs (Lu et al have isolated and identified 21444 distinct circRNA from laryngeal squamous cell carcinoma [248]) has led to great interest and intensification of research. Nath et al reported nine different circRNAs dysregulated in HNSCC tumors that may serve as potential prognostic markers of HNC [249]. Similar findings have been reported for Laryngeal Squamous Cell Carcinoma [250,251], Tongue Cancer [252], Nasopharyngeal Carcinoma [253,254], Hypopharyngeal Squamous Cell Carcinoma [255] and Oral Squamous Cell Carcinoma [256,257].…”

“…All the aforementioned intensive research and the attention gained by circRNA in relation to its role in HNC make it undoubtedly the second most popular, after microRNA, RNA molecule considered as a biomarker of the pathogenesis of head and neck cancers. Although miRNA is in the field of liquid biopsy at a much more advanced stage of research, circRNA is also considered an excellent biomarker, and the panels created as proposals for faster diagnostics [249] give hope for the usefulness of these molecules.…”

Circular RNA PVT1 Promotes Breast Cancer Progression via miR-30b-5p/AEG-1 Axis

“…Further dual luciferase reporter experiments indicated that miR-30b-5p was the target of circPVT1. MiR-30b-5p participated in malignant progression in a variety of cancers including pancreatic cancer [15], esophageal squamous cell carcinoma [16], papillary thyroid cancer [17]. In this study, miR-30b-5p inhibitors partially reversed circPVT1 depletion-mediated inhibition in breast cancer cells.…”

Integrated analysis of high‑throughput sequencing reveals the regulatory potential of hsa_circ_0035431 in HNSCC

“…In addition, a previous study demonstrated that circRNA/miRNA/mRNA networks are involved in the development and progression of multiple types of malignancy (7). Results of a meta-analysis demonstrated that nine circRNAs may serve as potential prognostic markers for HNSCC and these are associated with lower overall survival (OS) and poor clinicopathological outcomes in patients with HNSCC (8).…”