Identification of key candidate genes and small molecule drugs in cervical cancer by bioinformatics strategy

Abstract

PurposeCervical cancer (CC) is one of the most common malignant tumors among women. The present study aimed at integrating two expression profile datasets to identify critical genes and potential drugs in CC.Materials and methodsExpression profiles, GSE7803 and GSE9750, were integrated using bioinformatics methods, including differentially expressed genes analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and protein–protein interaction (PPI) network construction. Subsequently, survival analysis was performed among the key genes using Gene Expression Profiling Interactive Analysis websites. Connectivity Map (CMap) was used to query potential drugs for CC.ResultsA total of 145 upregulated genes and 135 downregulated genes in CC were identified. The functional changes of these differentially expressed genes related to CC were mainly associated with cell cycle, DNA replication, p53 signaling pathway, and oocyte meiosis. A PPI network was identified by STRING with 220 nodes and 2,111 edges. Thirteen key genes were identified as the intersecting genes of the enrichment pathways and the top 20 nodes in PPI network. Survival analysis revealed that high mRNA expression of MCM2, PCNA, and RFC4 was significantly associated with longer overall survival, and the survival was significantly better in the low-expression RRM2 group. Moreover, CMap predicted nine small molecules as possible adjuvant drugs to treat CC.ConclusionOur study found key dysregulated genes involved in CC and potential drugs to combat it, which might provide insights into CC pathogenesis and might shed light on potential CC treatments.

Potential mechanism of RRM2 for promoting Cervical Cancer based on weighted gene co-expression network analysis

“…Our results indicated that RRM2 is upregulated and significantly associated with poor prognosis in cervical cancer, and these results are in line with previous studies [18,19,36,40]. With 192 samples (29 normal, 30 low-grade dysplasia, 30 high-grade dysplasia and 103 invasive cancer tissue specimens) and SiHa cervical cancer cells, Su et al reported the expression of RRM2 in cancer tissues was increased when compared to high-grade dysplasia, low-grade dysplasia or normal cervical tissues [40].…”

“…They also found that downregulated RRM2 promoted apoptosis and cell cycle arrest, as well as inhibiting tumor formation. In addition, bioinformatics analyses also indicated that OS was significantly better in the low-expression RRM2 group [18,36].…”

A humanized yeast phenomic model of deoxycytidine kinase to predict genetic buffering of nucleoside analog cytotoxicity

“…5D; Table 3) included: (1) YTA7/ATAD2/ATAD2B , which localizes to chromatin and regulates histone gene expression. ATAD2 overexpression portends poor prognosis in gastric, colorectal, cervical, hepatocellular carcinoma, lung, and breast cancer, and thus overexpression sensitivity could represent the potential to target a driver gene [119-125]; (2) PIF1 / PIF1 , a DNA helicase, which is involved in telomere regulation and is required during oncogenic stress [113]; (3) RPS1B/RPS3A , which is a small subunit ribosomal protein that is overexpressed in hepatitis B associated hepatocellular carcinoma and non-small cell lung cancer [114,115]; (4) LEO1/LEO1 , which associates with the RNA polymerase II and acts as an oncogene in acute myelogenous leukemia [156]; (5) ELO3/ELOVL1/ELOVL2/ ELOVL4/ELOVL6 , which constitutes a family of fatty acid elongases that function in sphingolipid biosynthesis, among which ELOVL1 is overexpressed in breast and colorectal cancer tissue [107,108], ELOVL2 is upregulated in hepatocellular carcinoma [109], and ELOVL6 is overexpressed and associated with poor prognosis in liver and breast cancer [110,111] ; (6) MDL2/ABCB10 , which is a mitochondrial inner membrane ATP-binding cassette protein and is upregulated in breast cancer [112]; (7) CPR3/PPIA , which is a mitochondrial cyclophilin that is upregulated in lung cancer, esophageal, and pancreatic cancer [104-106]; and (8) SAC3/MCM3AP/SAC3D1 , which is a nuclear pore-associated protein functioning in transcription and mRNA export, with MCM3AP being upregulated in glioma cells [116], while SAC3D1 is upregulated in cervical cancer and hepatocellular carcinoma [117,118]. Yeast gene deletion suppression together with overexpression sensitivity of human homologs in cancer reveals potential therapeutic vulnerabilities that can be further explored in both systems.…”

Cervical cancer risk profiling: molecular biomarkers predicting the outcome of hrHPV infection

“…Furthermore, one new approach for the use of MCM2 as a biomarker is the detection of its gene in samples. Tang et alusing bioinformatics analysis, concluded that the MCM2 gene plays an essential role in cervical cancer, and it might represent an important marker for diagnosis [144].…”