Comprehensive analysis of circRNA expression pattern and circRNA-miRNA-mRNA network in oral squamous cell carcinoma
Comprehensive analysis of circRNA expression pattern and circRNA-miRNA-mRNA network in oral squamous cell carcinoma
复制标题
口腔鳞状细胞癌中circRNA表达模式及circRNA-miRNA-mRNA网络综合分析
DOI：
10.1016/j.oraloncology.2021.105437
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发表时间：
2021-07-13
期刊：
影响因子：
4.8
通讯作者：
Ma, Hongxia
中科院分区：
文献类型：
--
作者：
Li, Yuancheng;Gong, Linnan;Ma, Hongxia
目的：CircRNA是肿瘤发生和发展的重要基因调控因子。方法：采用CIRCexplorer 2 pipeline序列分析技术，对46例口腔鳞状细胞癌（oral squamous cell carcinoma，OSCC）组织中的circRNA进行分析。结果：在1276个高置信度的circRNA中，有154个在肿瘤和正常组织中差异表达（log（2）竖条Fold Change竖条>= 1，假发现率< 0.05）。与正常组织相比，肿瘤中的CircRNA表达整体下调（P = 9.44 x 10（-14））。相关性分析显示circRNA的表达与肿瘤浸润淋巴细胞（P = 1.10 × 10 - 4）和间质信号（P = 2.70 × 10 - 3）呈正相关，与细胞增殖标志物呈负相关（P = 4.32 × 10 - 2）。CircRNAs-miRNAs-mRNAs调控网络揭示了6574个相互作用，靶基因在细胞外基质和免疫相关通路中富集。对免疫相关通路中的靶基因进行生存分析，在癌症基因组图谱队列中，有20个基因与OSCC的预后状态显著相关。以上20个基因构建的风险模型与口腔鳞癌的预后状态相关（HR = 3.28，P = 5.06 × 10（-11）），并在独立研究中验证了结果（GSE41613）（HR = 2.06，P = 1.73 x 10（-2））。CircRNA在OSCC组织中表现出全局下调模式，受CircRNA调节的基因主要参与免疫和细胞外基质途径，这也可能影响OSCC的预后，表明它们可以作为潜在的预后生物标志物。
Objective: CircRNAs are critical gene modulators in tumor initiation and progression. However, the expression pattern and molecular pathogenesis of circRNAs in oral squamous cell carcinoma (OSCC) are still poorly characterized.Methods: RNA sequencing with CIRCexplorer2 pipeline was performed to identify circRNAs in 46 tumor-normal paired tissues from OSCC patients. Another set of 48 head and neck squamous cell carcinoma samples from the MiOncoCirc database were utilized as an independent validation.Results: Of the 1276 identified high-confidence circRNAs, 154 were differentially expressed between tumor and normal tissues (log(2)vertical bar Fold Change vertical bar >= 1 and false discovery rate < 0.05). CircRNAs expression was globally down-regulated in tumors compared to normal tissues (P = 9.44 x 10(-14)). Correlation analysis demonstrated that the global expression of circRNAs was positively related to tumor infiltrating lymphocyte (P = 1.10 x 10(-4)) and stromal signature (P = 2.70 x 10(-3)) whereas negatively associated with cell proliferation markers (P = 4.32 x 10(-2)). CircRNAs-miRNAs-mRNAs regulatory network revealed 6574 interactions, and the target genes were enriched in extracellular matrix and immune-related pathways. Survival analysis were performed on target genes in immune-related pathways, and 20 genes were significantly associated with the prognostic status of OSCC in The Cancer Genome Atlas cohort. The risk model constructed with above 20 genes was associated with the prognosis status of OSCC (HR = 3.28, P = 5.06 x 10(-11)), and the result was validated in an independent study (GSE41613) (HR = 2.06, P = 1.73 x 10(-2)).Conclusion: CircRNAs showed a global down-regulation pattern in OSCC tissues, and genes regulated by circRNAs primarily involved in immune and extracellular matrix pathways, which could also affect the OSCC prognosis, indicating that they may serve as potential prognostic biomarkers.