Screening and Discovery of New Potential Biomarkers and Small Molecule Drugs for Cervical Cancer: A Bioinformatics Analysis

• Published in: Technology in cancer research & treatment 2020, Vol.19, p.1533033820980112
• Main Authors: Qiu, Hui-Zhu, Huang, Ji, Xiang, Cheng-Cheng, Li, Rong, Zuo, Er-Dong, Zhang, Yuan, Shan, Li, Cheng, Xu
• Format: Article
• Language: English
• Subjects: Bioinformatics; Biomarkers; Biomarkers, Tumor; Cdc45 protein; Cell cycle; Cell Line, Tumor; Cervical cancer; Cervix; Computational Biology - methods; Databases, Genetic; DNA biosynthesis; DNA microarrays; Drug Discovery - methods; Drug Screening Assays, Antitumor - methods; Drugs; Female; Gene expression; Gene Expression Profiling; Gene Ontology; Gene Regulatory Networks - drug effects; Genomes; Humans; Immunohistochemistry; Medical prognosis; Metastases; Original; p53 Protein; Proliferating cell nuclear antigen; Protein interaction; Protein Interaction Mapping; Small Molecule Libraries; Transcriptome; Uterine Cervical Neoplasms - drug therapy; Uterine Cervical Neoplasms - genetics
• ISSN: 1533-0346; 1533-0338
• DOI: 10.1177/1533033820980112

Background: Cervical cancer (CC) is the second most common type of malignant tumor survival rate is low in advanced stage, metastatic, and recurrent CC patients. This study aimed at identifying potential genes and drugs for CC diagnosis and targeting therapies. Methods: Three GEO mRNA microarray datasets of CC tissues and non-cancerous tissues were analyzed for differentially expressed genes (DEGs) by limma package. GO (Gene Ontologies) and KEGG (Kyoto Encyclopedia of Genes and Genomes) were used to explore the relationships between the DEGs. Protein-protein interaction (PPI) of these genes was established by the STRING database. MCODE was used for screening significant modules in the PPI networks to select hub genes. Biochemical mechanisms of the hub genes were investigated with Metascape. GEPIA database was used for validating the core genes. According to these DEGs, molecular candidates for CC were recognized from the CMAP database. Results: We identified 309 overlapping DEGs in the 2 tissue-types. Pathway analysis revealed that the DEGs were involved in cell cycle, DNA replication, and p53 signaling. PPI networks between overlapping DEGs showed 68 high-connectivity DEGs that were chosen as hub genes. The GEPIA database showed that the expression levels of RRM2, CDC45, GINS2, HELLS, KNTC1, MCM2, MYBL2, PCNA, RAD54 L, RFC4, RFC5, TK1, TOP2A, and TYMS in CC tissues were significantly different from those in the healthy tissues and were significantly relevant to the OS of CC. We found 10 small molecules from the CMAP database that could change the trend of gene expression in CC tissues, including piperlongumine and chrysin. Conclusions: The 14 DEGs identified in this study could serve as novel prognosis biomarkers for the detection and forecasting of CC. Small molecule drugs like piperlongumine and chrysin could be potential therapeutic drugs for CC treatment.