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Am J Otolaryngol. 2019 Jul - Aug;40(4):547-554. doi: 10.1016/j.amjoto.2019.04.015. Epub 2019 Apr 23.

The molecular differences between human papillomavirus-positive and -negative oropharyngeal squamous cell carcinoma: A bioinformatics study.

Author information

1
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.
2
Department of Stomatology, Northeast Petroleum University Affiliated Hospital, Fazhan Road, High Tech District, 163000 Daqing City, Heilongjiang Province, China.
3
Department of Stomatology, The Heping Affiliated Hospital of Changzhi Medical College, Changzhi City, Shanxi Province, China.
4
Faculty of Dentistry, University of Hong Kong, Hong Kong, China; Dr D Y Patil Dental College and Hospital, Dr D Y Patil Vidyapeeth, Pimpri, Pune, India.
5
Department of Cariology, Endodontology and Periodontology, University Leipzig, Liebigstr. 12, 04103 Leipzig, Germany.
6
Saxon Incubator for Clinical Translation/Translational Centre for Regenerative Medicine, Leipzig University, Phillip-Rosenthal-Str. 55, Leipzig 04103, Germany.
7
Genomap Technologies, Kongjiang Road 1500, Yangpu District, Shanghai, China.
8
School of Dentistry, University of Michigan, USA.
9
Heart Center Leipzig, University of Leipzig, Strümpellstr. 39, 04289 Leipzig, Germany.
10
Department of Cariology, Endodontology and Periodontology, University Leipzig, Liebigstr. 12, 04103 Leipzig, Germany. Electronic address: Dirk.Ziebolz@medizin.uni-leipzig.de.
11
Laboratory of Molecular Cell Biology, Beijing Tibetan Hospital, China Tibetology Research Center, 218 Anwaixiaoguanbeili Street, Chaoyang, Beijing 100029, China. Electronic address: hellocean@hotmail.com.

Abstract

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.

KEYWORDS:

Genes; Human papillomavirus; Oropharyngeal squamous cell carcinoma; Pathways; miRNAs

PMID:
31036418
DOI:
10.1016/j.amjoto.2019.04.015
[Indexed for MEDLINE]

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