Abstract
BackgroundCervical cancer (CC) is the primary cause of death in women. This study sought to investigate the potential mechanism and prognostic genes of CC.MethodsWe downloaded four gene expression profiles from GEO. The RRA method was used to integrate and screen differentially expressed genes (DEGs) between CC and normal samples. Functional analysis was performed by clusterprofiler. We built PPI network by Search Tool for the Retrieval of Interacting Genes Database (STRING) and selected hub modules via Molecular COmplex Detection (MCODE). CMap database was used to find molecules with therapeutic potential for CC. The hub genes were validated in GEO datasets, Gene Expession Profiling Interactive Analysis (GEPIA), immunohistochemistry, Cox regression analysis, TCGA methylation analysis and ONCOMINE were carried out. ROC curve analysis and GSEA were also performed to describe the prognostic significance of hub genes.ResultsFunctional analysis revealed that 147 DEGs were significantly enriched in binding, cell proliferation, transcriptional activity and cell cycle regulation. PPI network screened 30 hub genes, with CDK1 having the strongest connectivity with CC. Cmap showed that apigenin, thioguanine and trichostatin A might be used to treat CC(P < 0.05). Eight genes (APOD, CXCL8, MMP1, MMP3, PLOD2, PTGDS, SNX10 and SPP1) were screened out through GEPIA. Of them, only PTGDS and SNX10 had not appeared in previous studies about CC. The validation in GEO showed that PTGDS showed low expression while SNX10 presented high expression in tumor tissues. Their expression profiles were consistent with the results in immunohistochemistry. ROC curve analysis indicated that the model had a good diagnostic efficiency (AUC = 0.738). GSEA analysis demonstrated that the two genes were correlated with the chemokine signaling pathway (P < 0.05). TCGA methylation analysis showed that patients with lowly-expressed and highly-methylated PTGDS had a worse prognosis than those with highly-expressed and lowly-methylated PTGDS (p = 0.037). Cox regression analysis showed that SNX10 and PTGDS were independent prognostic indicators for OS among CC patients (P = 0.007 and 0.003).ConclusionsPTGDS and SNX10 showed abnormal expression and methylation in CC. Both genes might have high prognostic value of CC patients.
Highlights
Cervical cancer (CC) is the primary cause of death in women
256 differentially expressed genes (DEGs) were filtered from GSE6791 (60 downregulated and 196 upregulated), 236 DEGs from GSE9750 (136 downregulated and 100 upregulated), 98 DEGs from GSE39001 (38 upregulated and 60 downregulated), 489 DEGs from GSE63514 (177 upregulated and 312 downregulated)
The results showed that Prostaglandin D synthase (PTGDS) had high expression levels in normal tissues and low expression levels in tumor tissues, while Sorting nexin 10 (SNX10) showed an opposite profile
Summary
Cervical cancer (CC) is the primary cause of death in women. This study sought to investigate the potential mechanism and prognostic genes of CC. An annual death toll of 265,700 makes cervical cancer (CC) the second deadliest malignancy in females [1]. Despite pre-cancerous screening and emerging treatments, CC remains the primary cause of death in women in developing countries [2]. It is of great significance to create new treatments of CC based on its to-be-clarified molecular mechanism. Effective analytic tools have been designed to explore tumor-associated genes, molecular mechanisms and target therapies. The integration of databases containing gene expression chips allows in-depth study of molecular mechanisms [3, 4]
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