Transcriptome profiling of the cancer and adjacent nontumor tissues from cervical squamous cell carcinoma patients by RNA sequencing
Cervical cancer is the third most common cancer and the fourth leading cause of cancer deaths among women in the world. The discovery of vital diagnostic and therapeutic markers against cervical squamous cell carcinoma (CSCC) would broaden our understanding on the molecular basis of CSCC. In this study, we thoroughly analyzed the transcriptome of CSCC and matched adjacent nontumor (ATN) tissue. RNA sequencing was performed to screen the differentially expressed genes (DEGs) of three pairs of CSCC and ATN tissues. Functional enrichment analysis was used to uncover the biological functions of DEGs. Protein interaction network was carried out to reveal interaction of DEGs. Quantitative real-time PCR was conducted to validate the expression of DEGs. Immunohistochemistry was used to detect the relationship between clinicopathological parameters of CSCC and DEGs. There were a total of 347 significantly common DEGs in the three paired examples, including 104 consistent upregulated and 148 consistent downregulated DEGs. The 347 DEGs were categorized into 73 functional categories by Gene Ontology (GO) analysis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis suggested six significantly signal pathways. The protein interaction network uncovered three important DEGs, including retinol dehydrogenase 12 (RDH12), ubiquitin D (UBD), and serum amyloid A1 (SAA1). We found that RDH12 expression was decreased in 74.5 % of CSCC tissues. RDH12 expression was negatively associated with tumor size and depth of cervical invasion. The UBD was overexpressed in 61.7 % of CSCC tissues and was positively related with tumor size and lymphatic metastasis. The SAA1 protein was overexpressed in 57.4 % of CSCC tissues and was positively related with clinicopathological parameters of tumor size, lymphatic metastasis, and depth of cervical invasion. The RDH12, UBD, and SAA1 genes might participate in the progression of CSCC.
KeywordsCervical squamous cell carcinoma Adjacent nontumor tissues Transcriptome Differentially expressed genes RNA sequencing
This research is supported by the National Natural Science Foundation of China (81472446).
Conflicts of interest
- 6.Plummer M, Schiffman M, Castle PE, Maucort-Boulch D, Wheeler CM, ALTS. Group. A 2-year prospective study of human papillomavirus persistence among women with a cytological diagnosis of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion. J Infect Dis. 2007;195:1582–9.CrossRefPubMedGoogle Scholar
- 7.de Freitas AC, Coimbra EC, Leitão MD. Molecular targets of HPV oncoproteins: potential biomarkers for cervical carcinogenesis. Biochim Biophys Acta. 1845;2014:91–103.Google Scholar
- 40.Lu SY, Rodriguez M, Liao WS. YY1 represses rat serum amyloid A1 gene transcription and is antagonized by NF-kappa B during acute-phase response. Mol Cell Biol. 1994;9:6523–63.Google Scholar