Nath Moumita, Roy Dibakar, Choudhury Yashmin
Department of Biotechnology, Assam University, Silchar, India.
Front Oncol. 2022 Feb 28;12:782439. doi: 10.3389/fonc.2022.782439. eCollection 2022.
Several 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).
816 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 ( 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.
The 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, = 0%; multivariate analysis: HR = 3.33, 95% CI: 2.54-4.38, p < 0.0001, = 0%), downregulated circRNA (univariate analysis: HR = 2.83, 95% CI: 1.73-4.65, p < 0.0001, = 57.8%; multivariate analysis: HR = 2.35, 95% CI: 1.42-3.89, p = 0.0009, = 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.
Nine 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.
多项研究报道了环状RNA（circRNA）在不同癌症的发病机制、诊断及预后中的作用。本荟萃分析旨在评估circRNA作为头颈部鳞状细胞癌（HNSCC）预后生物标志物的潜力。
从PubMed和Science Direct数据库检索到816篇相关文章，其中17篇符合纳入标准。采用纽卡斯尔-渥太华量表（NOS）系统对这17项研究进行质量评估，9项高质量研究（NOS>7）纳入荟萃分析。计算Cochran Q检验和I²统计量以检测研究间潜在的异质性。进行敏感性分析以验证结果的可信度，并用Begg漏斗图和Egger检验确定发表偏倚。采用风险比（HR）和95%置信区间（CI）通过单因素和多因素分析评估HNSCC患者的总生存期（OS）。
9种circRNA（circPVT1、circCORO1C、circ_0000199、circCUX1、circPARD3、circMYC、circ_0102272、circ_0092125和circ_00072387）的失调水平与HNSCC患者的OS呈负相关[circRNA上调（单因素分析：HR = 3.40，95%CI：2.66 - 4.36，p < 0.0001，I² = 0%；多因素分析：HR = 3.33，95%CI：2.54 - 4.38，p < 0.0001，I² = 0%），circRNA下调（单因素分析：HR = 2.83，95%CI：1.73 - 4.65，p < 0.0001，I² = 57.8%；多因素分析：HR = 2.35，95%CI：1.42 - 3.89，p = 0.0009，I² = 0%）]。这9种circRNA各自的HR表明与OS呈负相关，验证了总体HR。这些circRNA的失调水平还与不良临床病理结果相关，如原发肿瘤大小、淋巴结转移、远处转移以及不良的肿瘤（T）、淋巴结（N）、转移（M），即TNM分期，其中6种circRNA调控多种微小RNA，揭示了它们在肿瘤发生和癌症进展中的作用。
HNSCC肿瘤中失调的9种不同circRNA可能作为HNSCC潜在的预后标志物。这些标志物与HNSCC患者OS降低及不良临床病理结果相关。它们还通过多种机制参与HNSCC的发病机制和进展。
