人乳头瘤病毒阳性和阴性口咽鳞状细胞癌的分子差异：一项生物信息学研究。
The molecular differences between human papillomavirus-positive and -negative oropharyngeal squamous cell carcinoma: A bioinformatics study.
机构信息
The 16th Ward, Department of Ear, Nose and Throat (ENT), Daqing Oilfield General Hospital, Zhongkang Street No. 9, Saertu District, 163000, Daqing City, Heilongjiang Province, China.
Department of Stomatology, Northeast Petroleum University Affiliated Hospital, Fazhan Road, High Tech District, 163000 Daqing City, Heilongjiang Province, China.
出版信息
Am J Otolaryngol. 2019 Jul-Aug;40(4):547-554. doi: 10.1016/j.amjoto.2019.04.015. Epub 2019 Apr 23.
OBJECTIVE
To investigate the genetic and epigenetic differences between human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) and HPV-negative OPSCC.
METHODS
Microarray data of HPV-positive and -negative OPSCC were retrieved from NCBI GEO datasets. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DE-miRNAs) were identified by performing differential expression analysis. A functional enrichment analysis was performed to explore the biological processes and signaling pathways that DEGs and DE-miRNAs were involved in, respectively. A protein-protein interaction (PPI) network of DEGs was constructed to identify hub genes. miRNA-target network and miRNA-miRNA functional synergistic network were each constructed in order to identify risk-marker miRNAs. An miRNA-target-pathway network was constructed in order to explore the function of identified risk-marker miRNAs.
RESULTS
Microarray data from 3 datasets (GSE39366, GSE40774, and GSE55550) was included and analyzed. The PPI network identified 3 hub genes (VCAM1, UBD, and RPA2). MiR-107 and miR-142-3p were found to play the most significant role in both the DE-miRNA-target network as well as in the miRNA-miRNA functional synergistic network. MiR-107 was involved in HPV-induced tumorigenesis by targeting many genes (CAV1, CDK6, MYB, and SERPINB5) and regulating the p53 signaling pathway, the PI3K-Akt signaling pathway, and the autophagy pathway. In addition, miR-142-3p was implicated in HPV-induced tumorigenesis by targeting the PPFIA1 gene and regulating transcriptional dysregulation and other cancerous pathways.
CONCLUSION
Three genes (VCAM1, UBD, and RPA2), two miRNAs (miR-107 and miR-142-3p), and four pathways (p53, PI3K-Akt, autophagy, and transcription dysregulation in cancer) were identified to play critical roles in distinguishing HPV-positive OPSCC from HPV-negative OPSCC.
目的
探讨人乳头瘤病毒（HPV）阳性或阴性口咽鳞状细胞癌（OPSCC）之间的遗传和表观遗传差异。
方法
从 NCBI GEO 数据集检索 HPV 阳性和阴性 OPSCC 的微阵列数据。通过进行差异表达分析，确定差异表达基因（DEGs）和差异表达 miRNA（DE-miRNAs）。分别进行功能富集分析，以探讨 DEGs 和 DE-miRNAs 分别参与的生物学过程和信号通路。构建 DEGs 的蛋白质-蛋白质相互作用（PPI）网络，以识别关键基因。构建 miRNA-靶标网络和 miRNA-miRNA 功能协同网络，以识别风险标记 miRNA。构建 miRNA-靶标-通路网络，以探讨鉴定的风险标记 miRNA 的功能。
结果
纳入并分析了 3 个数据集（GSE39366、GSE40774 和 GSE55550）的微阵列数据。PPI 网络鉴定出 3 个关键基因（VCAM1、UBD 和 RPA2）。miR-107 和 miR-142-3p 分别在 DE-miRNA-靶标网络和 miRNA-miRNA 功能协同网络中发挥最重要的作用。miR-107 通过靶向许多基因（CAV1、CDK6、MYB 和 SERPINB5）并调节 p53 信号通路、PI3K-Akt 信号通路和自噬通路，参与 HPV 诱导的肿瘤发生。此外，miR-142-3p 通过靶向 PPFIA1 基因并调节转录失调和其他癌症途径，参与 HPV 诱导的肿瘤发生。
结论
鉴定出 3 个基因（VCAM1、UBD 和 RPA2）、2 个 miRNA（miR-107 和 miR-142-3p）和 4 个通路（p53、PI3K-Akt、自噬和癌症转录失调）在区分 HPV 阳性 OPSCC 与 HPV 阴性 OPSCC 中起关键作用。
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