异常表达的环状RNA作为肝细胞癌新型非侵入性生物标志物的Meta分析
Abnormally expressed circular RNAs as novel non-invasive biomarkers for hepatocellular carcinoma: A meta-analysis.
作者信息
Jiang Ya-Lin, Shang Meng-Meng, Dong Shi-Zhen, Chang Yong-Chao
机构信息
Department of Clinical Laboratory, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, Henan Province, China.
出版信息
World J Gastrointest Oncol. 2019 Oct 15;11(10):909-924. doi: 10.4251/wjgo.v11.i10.909.
BACKGROUND
Circular RNAs (circRNAs) are a newly discovered class of endogenous non-coding RNAs that may have roles in cancer genesis and development. In the recent literature, dysregulated circRNAs have been extensively investigated in hepatocellular carcinoma (HCC). Whether or not circRNAs are of clinical value for the management of HCC has not been characterized.
AIM
To meta-analyze the diagnostic and prognostic value of abnormally expressed circRNAs in HCC.
METHODS
Eligible studies were sourced from PubMed, EMBASE, and CNKI online databases. Data on patients' clinical characteristics, including diagnostic efficacy and overall survival, were extracted. The diagnostic and prognostic parameters were respectively synthesized using the bivariate meta-analysis model and multivariate Cox hazard regression analysis based on Stata 12.0. The trim and fill method was adopted to assess the possible effects from publication bias.
RESULTS
A total of 21 eligible studies were included. The pooled sensitivity, specificity, and area under the curve of abnormally expressed circRNAs in distinguishing HCC from non-cancer controls were 0.78 (95%CI: 0.69-0.85), 0.80 (95%CI: 0.74-0.86), and 0.86, respectively. Survival analyses showed that the down-regulated circRNA expression signature correlated perfectly with HCC survival [hazard ratio (HR) = 0.42, 95%CI: 0.19-0.91, = 0.028; = 92.7%, = 0.000], whereas the HCC cases with high circRNA levels had significantly poorer prognoses than those of patients with low circRNA levels (HR = 2.22, 95%CI: 1.50-3.30, = 0.000; = 91%, = 0.000). Moreover, abnormally expressed circRNAs were intimately associated with tumor size, differentiation grade, microvascular invasion, metastasis, TNM stage, and serum alpha fetal protein level in patients with HCC. Stratified analysis based on sample type, control source, and expression status also yielded robust results.
CONCLUSION
Abnormally expressed circRNA signatures show immense potential as novel non-invasive biomarker(s) for HCC diagnosis and prognosis.
背景
环状RNA（circRNAs）是一类新发现的内源性非编码RNA，可能在癌症的发生和发展中发挥作用。在最近的文献中，失调的circRNAs已在肝细胞癌（HCC）中得到广泛研究。circRNAs对HCC治疗是否具有临床价值尚未明确。
目的
对异常表达的circRNAs在HCC中的诊断和预后价值进行Meta分析。
方法
从PubMed、EMBASE和CNKI在线数据库中获取符合条件的研究。提取患者的临床特征数据，包括诊断效能和总生存期。使用双变量Meta分析模型和基于Stata 12.0的多变量Cox风险回归分析分别综合诊断和预后参数。采用剪补法评估发表偏倚可能产生的影响。
结果
共纳入21项符合条件的研究。异常表达的circRNAs在区分HCC与非癌对照中的合并敏感性、特异性和曲线下面积分别为0.78（95%CI：0.69 - 0.85）、0.80（95%CI：0.74 - 0.86）和0.86。生存分析表明，circRNA表达下调特征与HCC生存密切相关[风险比（HR）= 0.42，95%CI：0.19 - 0.91，P = 0.028；I² = 92.7%，P = 0.000]，而circRNA水平高的HCC患者预后明显比circRNA水平低的患者差（HR = 2.22，95%CI：1.50 - 3.30，P = 0.000；I² = 91%，P = 0.000）。此外，异常表达的circRNAs与HCC患者的肿瘤大小、分化程度、微血管侵犯、转移、TNM分期和血清甲胎蛋白水平密切相关。基于样本类型、对照来源和表达状态的分层分析也得出了可靠的结果。
结论
异常表达的circRNA特征作为HCC诊断和预后的新型非侵入性生物标志物具有巨大潜力。
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