IMR Press / EJGO / Volume 41 / Issue 6 / DOI: 10.31083/j.ejgo.2020.06.5416
Open Access Original Research
Transcriptome sequencing reveals pathways and genes dysregulated in HPV infected cervical cancer
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1 Basic Medical College, Southwest Medical University, 646099 Sichuan, China
2 Pathology Department of the First Affiliated Hospital, Southwest Medical University, 646099 Sichuan, China
Eur. J. Gynaecol. Oncol. 2020, 41(6), 996–1003; https://doi.org/10.31083/j.ejgo.2020.06.5416
Accepted: 26 May 2020 | Published: 15 December 2020
Abstract

Objective: Cervical cancer is the fourth leading cause of cancer mortality in women worldwide. Cervical cancer is predominately caused by chronic infection with high-risk human papillomavirus (HR-HPV) genotypes. While several oncogenes and tumor suppressors are implicated in the initiation and progression of cervical cancer, the complicated genetic network regulating cancer is largely unknown. We aimed to study these oncogenes and tumor suppressors. Materials and methods: We extracted mRNA from paraffin-embedded tissues derived from cervical cancers infected with HPV-16, HPV-58, HPV-52, HPV-33 and HPV-35 and normal controls. Transcriptome sequencing was undertaken to analyze the differentially expressed genes (DEGs) between cancer and normal tissues. Results: Transcriptomic analysis screened 10,025 DEGs between cancerous and normal tissues (5,419 upregulated and 4606 downregulated). In KEGG analysis, most of the annotated DEGs were enriched in four sub-categories involved in MAPK, mTOR, PI3K-Akt, and Ras signaling pathways. And most of the key genes in these pathways were dysregulated at the mRNA level, including FGFR3, PDK2, PDK3, Akt1, Ras, MAPK1, MAPK3 and mTOR. The GO classification, KEGG enrichment and DEGs profiles of HPV-58 infected samples aligned closer to those of HPV-16 infected but were different from those of tissues infected with the other HPVs. Conclusions: These results suggest that the genesis of cervical cancer is associated with gene expression changes in specific cancer related signaling pathways. Thus, developing biomarkers and targets from these pathways may aide the diagnosis and targeted treatment of cervical cancers.

Keywords
Cervical cancer
Human papillomavirus
Transcriptome sequencing
Differentially expressed genes
Signaling pathway
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