Abstract
Cervical cancer remains a primary cause of female death in developing countries, but its prognosis can be greatly improved if patients are diagnosed earlier. In the present study, we screened the common differentially expressed genes (DEGs) of cervical squamous cell carcinoma (CESC) from dataset GSE7803, Gene Expression Omnibus, and The Cancer Genome Atlas databases. An integrated bioinformatics analysis was performed based on these DEGs for their enrichment in functions and pathways, interaction network, prognostic signature, and candidate molecular drugs. As a result, 164 (114 upregulated and 47 downregulated) DEGs of CESC were identified for further investigation. We then conducted the gene ontology term enrichment and Kyoto Encyclopedia of Genes and Genomes Pathway analyses to reveal the underlying functions and pathways of these DEGs. In the protein-protein interaction network, hub module and hub genes were identified. Five genes of significant prognostic value-DSG2, ITM2A, CENPM, RIBC2, and MEIS2-were identified by prognostic signature analysis and used to construct a risk linear model. Further validation and investigation suggested DSG2 might be a key gene in CESC prognosis. We then identified two candidate small molecules (trichostatin A and tanespimycin) against CESC. Further validation and exploration of these hub genes are warranted for future prospect in clinical applications.
Highlights
Cervical cancer is the most prevalent female cancer worldwide, and cervical squamous cell carcinoma (CESC) is the most common histological type of cervical cancer
618 differentially expressed genes (DEGs) (329 upregulated and 289 downregulated ones) were screened in GSE7803 and 1921 DEGs (712 upregulated and 1209 downregulated genes) in The Cancer Genome Atlas (TCGA) database
We comprehensively analyzed the DEGs in GSE7803 and TCGA, and screened 161 overlapped DEGs (114 upregulated and 47 downregulated genes) (Supplementary Fig. S5)
Summary
Cervical cancer is the most prevalent female cancer worldwide, and cervical squamous cell carcinoma (CESC) is the most common histological type of cervical cancer. The spread of cervical cancer screening and advanced medical treatment has significantly improved the prognosis of patients, especially those in developed countries, where a 60% reduction in mortality can be achieved. Poor prognosis and a high recurrence rate remain a challenge in developing countries (Siegel et al, 2016). There are a few biomarkers [such as squamous cell carcinoma antigen (SCC-Ag)] that are used in the diagnosis and prognosis of cervical cancer. The absence of sensitivity and specificity of these biomarkers limits their utility (Salvatici et al, 2016). It is critical to find more reliable and effective biomarkers to improve early diagnosis and prognosis of cervical cancer
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